Medicine and Health Sciences Commons^™

Nicotinic Receptor Antagonists In The Treatment Of Neuropharmacological Disorders, Peter A. Crooks, Linda P. Dwoskin, Alain Ravard

Pharmaceutical Sciences Faculty Patents

Nicotine analogs that have nicotinic receptor antagonist properties. These compounds have been shown to competitively inhibit dopamine release induced by nicotine. The nicotine analog compounds are useful in the treatment of nicotine abuse, smoking cessation therapy, as an antidote for nicotine intoxication, treatment of cognitive disorders such as Alzheimer's disease and for the treatment of Parkinson's disease.

Triazine Herbicide Exposure And Breast Cancer Incidence: An Ecologic Study Of Kentucky Counties, Michele A. Kettles, Steven R. Browning, Timothy Scott Prince, Sanford W. Horstman

Preventive Medicine and Environmental Health Faculty Publications

The incidence of breast cancer in the United States has steadily increased for the past three decades. Exposure to excess estrogen, in both natural and synthetic forms, has been implicated as a risk factor for the development of this disease. Considerable interest has been focused on organochlorines, such as the triazine herbicides, and their possible role in the initiation or promotion of human breast cancer. To explore this relationship, an ecologic study of Kentucky counties was designed. Exposure to triazines was estimated by use of water contamination data, corn crop production, and pesticide use data. A summary index of triazine …

Farmer Crushed When Run Over By Tractor And Disc, Kentucky Injury Prevention And Research Center

Fatality Case Reports--Tractors/Logging

A 75-year-old farmer was killed when he was run over by a tractor and disc attachment. The farmer attempted to start the engine on a tractor while he stood on the ground beside it, a practice which was not unusual for him. The transmission had been left in gear and when the ignition was started the tractor lurched forward knocking the victim to the ground. The tractor continued to move forward, running over the victim. His wife went to search for him when she realized he had been gone from the house for quite some time. She found him in …

Role Of Egr-1 Gene Expression In B Cell Receptor-Induced Apoptosis In An Immature B Cell Lymphoma, Subramanian Muthukkumar, Seong-Su Han, Sumathi Muthukkumar, Vivek M. Rangnekar, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Ligation of B cell receptor (BCR) on BKS-2, an immature B cell lymphoma by anti-IgM antibodies (Ab) caused apoptosis. Here we report that signaling through B cell receptor in wild type BKS-2 cells down-regulated the expression of Egr-1, a zinc finger-containing transcription factor. A reduction in the level ofEgr-1 mRNA could be demonstrated as early as 30 min after the ligation of BCR on BKS-2 cells. Immunocytochemical and Western blot analysis revealed that the expression of EGR-1 protein was also inhibited by anti-IgM treatment. Antisense oligonucleotides to Egr-1 caused growth inhibition and apoptosis in BKS-2 cells, suggesting that …

Permeable, Non-Irritating Prodrugs Of Nonsteroidal And Steroidal Agents, Paul Ashton, Thomas J. Smith, Peter G. Glavinos, John D. Conklin, Peter A. Crooks, Robert M. Riggs, Tadeusz Cynkowski, Grazyna Cynkowska

Ophthalmology and Visual Science Faculty Patents

Prodrugs containing an active drug molecule linked to a polyethylene glycol group, and a method of use thereof are described. Exemplary soluble ester prodrugs contain naproxen, triamcinolone acetonide, gancyclovir, taxol, cyclosporin, dideoxyinosine, trihydroxy steroids, and flurbiprofen molecules linked to polyethylene glycol (PEG) groups. Pharmaceutical compositions containing these prodrugs, and a method of using these esters for treating disease states or symptoms are also described.

Spin Trapping Compounds, John M. Carney, Robert A. Floyd

Pharmacology and Nutritional Sciences Faculty Patents

Compositions containing as the active ingredient a spin-trapping reagent, preferably α-phenyl butyl nitrone (PBN) or spin-trapping derivatives thereof, in a suitable pharmaceutical carrier for administration to a patient are disclosed for treating or preventing symptoms associated with aging or other conditions associated with oxidative tissue damage. Other spin-trapping agents can also be used, such as 5,5-dimethyl pyrroline N-oxide (DMPO) or α-(4-pyridyl 1-oxide)-N-tert-butylnitrone (POBN), and other spin-trapping derivatives thereof. These compositions and methods are useful in the treatment of age-related disorders, pre-surgical and/or pre-anesthetic preparation or administration of chemotherapeutic agents, and in the treatment of disorders or trauma of the brain, …

Multicompartment Hard Capsule With Control Release Properties, George Digenis, Dagmar Noskova

Pharmaceutical Sciences Faculty Patents

The present invention relates to a hard capsule made from a material such as gelatin, starch or a hydrophilic polymer. The capsule of the present invention is formulated into a delivery system which incorporates pharmacologically active components in three or more distinct compartments. When three compartments are utilized in the capsule, the outer compartment incorporates a drug and excipients into a layer which coats the outer part of the capsule. This layer represents the rapid release portion of the delivery system. The intermediate compartment comprises a powder formulation comprised of a drug and excipients which represents the intermediary speed release …

Metabolically Inactive Insulin Analog Prevents Type I Diabetes In Prediabetic Nod Mice, Dennis G. Karounos, J. Scott Bryson, D. A. Cohen

Internal Medicine Faculty Publications

The purpose of this study was to determine the relative importance of the metabolic effects of insulin for diabetes prevention by administering insulin or an inactive insulin analog by daily subcutaneous injections to prediabetic mice. A recombinant monomeric human insulin analog, which does not bind to the insulin receptor as a consequence of an alteration of a single amino acid at position 25 of the B chain, was shown to be equally effective at diabetes prevention as was intact insulin. In contrast to native insulin, the insulin analog did not cause hypoglycemia after subcutaneous injection. The insulin analog, however, protected …

Use Of Rollover Protective Structures -- Iowa, Kentucky, New York, And Ohio, 1992-1997, Craig Zwerling, Leon Burmeister, S. Reynolds, Robert H. Mcknight, Steven R. Browning, Deborah Reed, John Wilkins Iii, T. Bean, L. Mitchell, Eric Hallman, John J. May, A. Stark

Preventive Medicine and Environmental Health Faculty Publications

Agriculture has one of the highest occupational fatality rates of all industries in the United States (1). Tractors and other types of agricultural equipment account for a large proportion of these fatalities, and farm-tractor rollovers account for approximately 130 work-related deaths each year in the United States (2). Although rollover protective structures (ROPS) are effective in protecting tractor operators from fatal injuries during rollovers (3-5), most tractors in the United States are not equipped with ROPS (4-7). Beginning in 1985, tractor manufacturers in the United Sates agreed to sell only tractors with ROPS; however, many older tractors without ROPS remain …

Potential Role Of Tnfα And Lipoprotein Lipase As Candidate Genes For Obesity, Philip A. Kern

Clinical and Translational Science Faculty Publications

To maintain body weight, metabolic efficiency was promoted during evolution; two candidate genes for body weight regulation are lipoprotein lipase (LPL) and tumor necrosis factor-α [TNFα). Human fat cells do not synthesize lipid, but rely on LPL-mediated plasma triglyceride hydrolysis. Adipose LPL is elevated in obesity. Following weight loss, LPL is elevated further, suggesting attempts to maintain lipid stores during fasting and to replenish lipid stores during refeeding. Muscle LPL is regulated inversely to adipose LPL. Thus, an increased adipose/muscle LPL ratio would partition dietary lipid into adipose tissue and would explain some of the variability in weight gain when …

Identification Of A Gal/Galnac Lectin In The Protozoan Hartmannella Vermiformis As A Potential Receptor For Attachment And Invasion By The Legionnaires' Disease Bacterium, Chandrasekar Venkataraman, Bradley J. Haack, Subbarao Bondada, Yousef Abu Kwaik

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The Legionnaire's disease bacterium, Legionella pneumophila, is a facultative intracellular pathogen which invades and replicates within two evolutionarily distant hosts, free-living protozoa and mammalian cells. Invasion and intracellular replication within protozoa are thought to be major factors in the transmission of Legionnaire's disease. Although attachment and invasion of human macrophages by L. pneumophila is mediated in part by the complement receptors CR1 and CR3, the protozoan receptor involved in bacterial attachment and invasion has not been identified. To define the molecular events involved in invasion of protozoa by L. pneumophila, we examined the role of protein tyrosine phosphorylation …

Intrinsic And Extrinsic Control Of Hemopoietic Stem Cell Numbers: Mapping Of A Stem Cell Gene, Gerald De Haan, Gary Van Zant

Markey Cancer Center Faculty Publications

We evaluated in vivo interactions between extrinsic (growth factor induced) and intrinsic (genetically determined) effectors of mouse primitive hemopoietic stem cell proliferation and numbers. Accordingly, stem cell frequency and cell cycle kinetics were assessed in eight strains of inbred mice using the cobblestone area–forming cell (CAFC) assay. A strong inverse correlation was observed between mouse lifespan and the number of autonomously cycling progenitors (CAFC day 7) in the femur. The population size of primitive stem cells (CAFC day 35) varied widely (up to sevenfold) among strains, unlike total CAFC day 7 numbers (cycling and quiescent), which were similar. Administration of …

Method For Employing The Delta Opioid Dadle To Extend Tissue Survival Time During Ischemia, Sufan Chien

Surgery Faculty Patents

This invention concerns a method for extending the survival time of mammalian lung tissue subjected to ischemia, by which said tissue is perfused with a preservation solution comprising a therapeutic dose of the delta opioid DADLE ([D-Ala²,D-Leu⁵]-Enkephalin) under hypothermic conditions.

Rear Tractor Rollover Kills Farmer, Kentucky Injury Prevention And Research Center

Fatality Case Reports--Tractors/Logging

A 67-year-old male farmer (the victim) died when the tractor he was operating flipped over backward, pinning him between it and another tractor. He and his 13-year-old grandson had been working with a tractor and rotary mower, but got stuck in the mud of a creek bed; approximately one-third of the rear tractor tires were buried in mud. He had gotten a second tractor, attached a chain from the rear of it to the front of the first tractor, and had just begun to try and pull the tractor out when the incident occurred. From evidence at the scene it …

Aminoalkylpyridine Compounds Which Are Useful As Anticonvulsant Drugs, Excitatory Amino Acid Inhibitors And Nmda Sigma Receptor Antagonists, Pankaja K. Kadaba

Pharmaceutical Sciences Faculty Patents

Pharmaceutical compositions comprise as the active ingredient potent orally active, nonneurotoxic anticonvulsant compounds that are excitatory amino acid and NMDA/sigma receptor antagonists . . .

To read the remainder of this abstract, please download this patent.

Tractor/Baler Operator Killed In Entanglement, Kentucky Injury Prevention And Research Center

Fatality Case Reports--Tractors/Logging

An 80-year-old full-time farmer died after being caught under a baler. The victim worked closely with his son on the 300-acre farm. He was working alone, driving a tractor with a baler attached, in an 8-acre field during a midafternoon in May. Having completed a portion of the field in the morning, the victim returned to the field after lunch to complete the task. Rain was forecast and the remainder of the field would take 4-5 hours to complete. The victim's son went to a nearby town to pick up parts for the round baler while the victim used a …

Hybrid Vector And Method Resulting In Protein Overproduction By Eukaryotic Cells, Robert E. Rhoads, Arrico De Benedetti

Molecular and Cellular Biochemistry Faculty Patents

A hybrid vector carrying a first and second DNA segments operationally linked thereto, the first DNA segment encoding a protein capable of cross-linking to the cap structure of mRNA and mediating ribosome-binding, and the second DNA segment encoding a polypeptide or protein, the vector being capable of replication, transcription and translation to express the factor and the polypeptide or protein upon transformation of a eukaryotic host, and the polypeptide or protein being expressed at a level higher than the level of expression thereof in the absence of the first DNA segment. A eukaryotic host is transformed with this hybrid vector. …

Logger Killed When Struck By Tree Limb During Hauling, Kentucky Injury Prevention And Research Center

Fatality Case Reports--Tractors/Logging

A 52-year-old male was killed on a logging site when a tree limb struck him in the back of the head. He had no previous logging experience and had been working with his friend who was a full-time logger for six days when the fatal incident occurred. The two men were working alone on the logging site and it was about 5:30 pm when they chained a load of three logs to the bulldozer to be dragged downhill to be loaded on a truck. A branch that was about 8 feet long and 4-5 inches in diameter stuck out of …

Farmer Killed When Tractor Slides Over Embankment While Mowing, Kentucky Injury Prevention And Research Center

Fatality Case Reports--Tractors/Logging

A 56-year-old part-time farmer was killed when the tractor he was driving overturned while mowing. Using a rotary mower attached to the John Deere 1520 tractor, the farmer mowed an area near the roadway that had a gradual downward slope. The tractor was not equipped with a Rollover Protective Structure (ROPS) or seatbelt. After mowing two rows, he made a left turn to begin the third pass when the back tire began to slip in the moist soil underneath the grass. Due to the momentum and weight of the tractor and attachment, the farmer was unable to stop the vehicle. …

!!Tractor Hazard Alert!!, Kentucky Injury Prevention And Research Center

Kentucky Haz Alerts--Tractors/Logging

Since January, at least six Kentucky farmers have been killed in tractor rollovers in which terrain changes caused by recent heavy rainfalls were a factor. In addition to mud and wet, slick grass, the rain created marshy areas and holes where none had been before; often these places are invisible due to weeds and tall grass.

Regulation Of The Rat Liver Sodium-Dependent Bile Acid Cotransporter Gene By Prolactin. Mediation Of Transcriptional Activation By Stat5, Tanmoy C. Ganguly, Michelle L. O'Brien, Saul J. Karpen, James F. Hyde, Fredrick J. Suchy, Mary Vore

Toxicology and Cancer Biology Faculty Publications

The intracellular mechanism(s) underlying the upregulation of the hepatic Na+/taurocholate cotransporting polypeptide (ntcp) by prolactin (PRL) are unknown. In this report, we demonstrate a time-dependent increase in nuclear translocation of phosphorylated liver Stat5 (a member of the ignal ransducers and ctivators of ranscription family) that correlated with suckling-induced increases in serum PRL levels. In electrophoretic mobility gel shift assays, nuclear Stat5 exhibited specific DNA-binding ability towards IFN-gamma-activated sequence (GAS)-like elements (GLEs; 5'TTC/A-PyNPu-G/TAA-3') located in the -937 to -904 bp region of the ntcp promoter. Transient cotransfections in HepG2 cells revealed that PRL inducibility (2.5-3-fold) required coexpression of the long form …

Bulldozer Operator Killed In Rollover, Kentucky Injury Prevention And Research Center

Fatality Case Reports--Other

A 56-year-old bulldozer operator was killed while clearing land on a steep hillside. He was self-employed and used the John Deere 450C bulldozer that he owned for logging on his own property, as well as doing work for others when needed. He owned mountain property near his home and he used the bulldozer to clear a series of paths in the hills for logging. At approximately 8 pm on the day of the incident, he was using the bulldozer to clear a path leading downhill where he planned to put a sawmill. As he was grading, he backed the bulldozer …

Farmer Killed When Tractor Overturns On Embankment, Kentucky Injury Prevention And Research Center

Fatality Case Reports--Tractors/Logging

A 44-year-old cattle farmer was killed when the tricycle tractor he was operating overturned. As was his usual practice, the victim had backed the tractor out of the shed near his home, turned to the right and was driving forward, down the embankment to the road which led to the highway. His cattle barn and pasture were located a short distance from his house (1-2 miles), and he regularly drove the tractor there to tend the cattle. On this day, however, the tractor flipped as he came over the embankment, rolling onto the victim. He died at the scene. In …

Sawmill Worker Killed By Circular Saw, Kentucky Injury Prevention And Research Center

Fatality Case Reports--Other

A 32-year-old laborer (the victim) at a sawmill died as a result of injuries received when he lost his balance and fell onto the log carriage directly in front of the 56-inch circular saw. He had been using a cane hook to turn the logs for repeated passes through the saw. After hooking a log, he somehow lost his balance and fell backward onto the carriage; the saw cut him from his shoulders through his midsection. A co-worker (the sawyer) was present, but had been facing another direction and did not see the victim fall. When the sawyer turned around …

Farmer Killed When Tractor Turns Over, Kentucky Injury Prevention And Research Center

Fatality Case Reports--Tractors/Logging

A 56-year-old farmer was killed when the tricycle tractor he was operating on a hillside overturned. He had been going up and down the hill to bring loads of dirt in the tractor's front-end loader in order to bury a calf. The hillside was relatively steep, and the ground was wet from recent rains. As he attempted to turn with the loader filled and raised, the tractor rolled over several times, crushing the victim. He died at the scene. In order to prevent similar incidents, the FACE investigator recommends:

• Older tractors should be retrofitted with rollover protective structures (ROPS) and …

Spin Trapping Pharmaceutical Compositions And Methods For Use Thereof, John M. Carney, Robert A. Floyd

Pharmacology and Nutritional Sciences Faculty Patents

Spin trapping compositions in general have now been discovered to be effective in treating a variety of disorders, including disorders such as those arising from ischemia, infection, inflammation, exposure to radiation or cytotoxic compounds, not just of the central and peripheral nervous systems but of peripheral organ disease having a wide variety of etiologies. In the preferred embodiment, the compositions for treating tissue damage from ischemia contain PBN, or active derivatives thereof, in a suitable pharmaceutical carrier for intravenous, oral, topical, or nasal/pulmonary administration. Many different disorders can be treated using these compounds, including diseases or disorders of the central …

Logger Killed During Tree Felling, Kentucky Injury Prevention And Research Center

Fatality Case Reports--Tractors/Logging

A 61-year-old male logger was killed when he was hit by the tree he was felling. On the day of the incident, he was working on a steep mountainside with his son and another logger. At approximately 10 am, the victim was felling a tree approximately 14 inches in diameter. As viewed from the bottom of the hill, a small tree about 6 inches in diameter stood about 6 feet to the right of the tree that was being felled. Lying on the ground directly behind those two vertical trees was a log 4-5 inches in diameter; it lay perpendicular …

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

Microbiology, Immunology and Molecular Genetics Faculty Patents

The present invention relates isolation of anti-idiotypic antibody 1A7 raised against anti-GD2 mAb 14G2a and its use for the treatment of melanoma and small cell carcinoma. The antibody may be used as a substitute for isolated purified GD2 antigen in any appropriate application.

Farmer Killed On Tractor During Logging Operations, Kentucky Injury Prevention And Research Center

Fatality Case Reports--Tractors/Logging

A 21-year-old male was killed when he and his 19-year-old brother were engaged in logging activities their grandparents' farmland. They both had grown up helping with the family farm and for the last two years their primary source of income was cutting trees on the land to sell for firewood. After cutting down the trees, the normal routine was for the younger brother to operate the tractor to pull the trees to a clearing where they would be cut into pieces. Although the victim had experience operating tractors, he had never performed that particular task. Because there was no drawbar …

Pug Mill Operator Killed After Entanglement, Kentucky Injury Prevention And Research Center

Fatality Case Reports--Other

On November 19, 1996, a 25-­year­-old female pug mill operator at a brick manufacturing plant was killed after her clothing became caught in a rotating shaft. She was strangled as the rotating shaft tightened her clothing around her neck, restricting her airway. In order to prevent similar incidents from occurring, FACE investigators recommend:

• Machines with rotating parts should have guards to prevent worker contact
• Employers should designate a competent person to conduct regular safety inspections and coordinate routine safety and injury prevention meetings
• Employers should provide a kill switch (panic bar) within reach of the pug mill that stops the …