Medicine and Health Sciences Commons^™

Farnesyl Pyrophosphate Analogs, Hans Peter Spielmann, Douglas A. Andres, Kareem A.H. Chehade

Molecular and Cellular Biochemistry Faculty Patents

The post-translational addition of a farnesyl moiety to the Ras oncoprotein is essential for its membrane localization and is required for both its biological activity and ability to induce malignant transformation. The present invention describes design and synthesis of a farnesylpyrophosphate (FPP) analog, 8-anilinogeranyl pyrophosphate (AGPP) that is transferred to Ras by farnesyltransferase (FTase), in which the ω-terminal isoprene unit of the farnesyl group has been replaced with an aniline functionality. AGPP potently inhibited FTase activity in vitro (IC₅₀=0.6 μM) and is highly selective showing little inhibitory activity against either geranylgeranyl-protein transferase type I (GGTase I) (IC_{50 …}

Iodo-Nonoxynol-9-Derivatives And Methods For Their Use, George Digenis, Philip Fowler, Kazuya Matsumoto, Gustavo Doncel

Pharmaceutical Sciences Faculty Patents

Mono- and di-iodinated nonoxynol-9-derivatives and methods for their use are disclosed.

Tractor Driving Among Kentucky Farm Youth: Results From The Farm Family Health And Hazard Surveillance Project, Steven R. Browning, Susan C. Westneat, Raeanne Szeluga

Epidemiology and Environmental Health Faculty Publications

This article documents the extent of children's involvement in tractor operations among a representative sample of Kentucky children living and working on family farms. Specifically, we describe children's exposures to tractor-related work activities, profile their use of the tractor (number of days worked), and assess compliance with generally recommended safety measures, such as using tractors equipped with ROPS (rollover protective structures), avoiding riding as passengers on tractors, and operating tractors on public roadways. Data for this study were collected in 1994 and 1995 as part of the NIOSH-sponsored Farm Family Health and Hazard Surveillance Project (FFHHSP). Despite recognition in the …

Neuronal Cell Model And Methods Of Use Therefor, Craig S. Miller, Robert J. Danaher, Robert J. Jacob

Microbiology, Immunology and Molecular Genetics Faculty Patents

The present invention provides, inter alia, a PC12 cell quiescently infected with a neurotropic virus. Preferred quiescently-infected neural cells are those wherein the neurotropic virus is a neurotropic herpes virus. Methods related to these and other materials are also provided.

Diagnostic Test And Therapy For Manganese Superoxide Dismutate (Msod) Associated Diseases, Daret K. St. Clair, Muneyasu Urano, Edward J. Kasarskis

Toxicology and Cancer Biology Faculty Patents

The present invention provides a diagnostic method and a kit for detection of mutations localized within the 5′ promoter region of the MnSOD gene. Such mutations are associated with diseases characterized by decreased MnSOD activity such as certain formes of cancer, and ALS. Accordingly, the diagnostic method this invention provides, comprising RFLP, direct sequencing, or PCR analysis of the region within 3 kb, the transcription initiation site will detect these disorders. This invention also provides a therapeutic method for such disorders comprising transfection of affected cells or tissues with high activity, MnSOD expression vectors, or the administration of exogenous MnSOD …

The Toxoplasma Gondii Protein Rop2 Mediates Host Organelle Association With The Parasitophorous Vacuole Membrane, Anthony P. Sinai, Keith A. Joiner

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Toxoplasma gondii replicates within a specialized vacuole surrounded by the parasitophorous vacuole membrane (PVM). The PVM forms intimate interactions with host mitochondria and endoplasmic reticulum (ER) in a process termed PVM–organelle association. In this study we identify a likely mediator of this process, the parasite protein ROP2. ROP2, which is localized to the PVM, is secreted from anterior organelles termed rhoptries during parasite invasion into host cells. The NH₂-terminal domain of ROP2 (ROP2hc) within the PVM is exposed to the host cell cytosol, and has characteristics of a mitochondrial targeting signal. In in vitro assays, ROP2hc is …

Protection Against Traumatic Brain Injury, Stephen William Scheff

Sanders-Brown Center on Aging Faculty Patents

The present invention relates to therapeutic uses of cyclosporin A to reduce adverse effects of neural injury.

The Kentucky Plan: An Innovative Approach To Professional Doctoral Education In Public Health., Joel M. Lee, F. Douglas Scutchfield

Preventive Medicine and Environmental Health Faculty Publications

The Doctor of Public Health (Dr.P.H.) degree is designed to prepare graduates for the highest levels of leadership in public health related careers in both public and private settings. The Kentucky School of Public Health has developed an innovative generalist professional degree program offering an extensive battery of courses based on the body of professional public health knowledge. The degree includes extensive supervised field experience as part of the academic training, linking theory with practice. Issues related to professional degrees, curriculum, accreditation and certification, admission, evaluation, plans for institutional cooperation, and demand are addressed.

Attitudes Towards Guns: Associations With Alcohol Use And Impulsive Behaviors, Catherine A. Martin, Arch G. Mainous, Harriett H. Ford, Rosalie Mainous, Susan Slade, David Martin, Hatim A. Omar

Psychiatry Faculty Publications

This study was an investigation of the association of attitudes toward guns with self-reports of alcohol/drug use, and impulsivity. Participants included 160 male and female high school students, who completed five questions regarding attitudes toward guns, in addition to questions about alcohol/drug use. Data were analyzed using t-tests. Males were more likely to feel that a home was safer with a gun. Feeling positively about a gun was associated with alcohol use in males and impulsive, aggressive behavior in males and females. A greater understanding of attitudes toward guns must take into account gender, alcohol use, and impulsive and aggressive …

Tetrafluoroazidoaniline And Method Of Making And Using The Same, Hans Peter Spielmann, Kareem A.H. Chehade

Molecular and Cellular Biochemistry Faculty Patents

The invention is directed to a novel compounds comprising 4-azidotetrafluoroaniline and the alkyl, acyl and sulfonamide derivatives thereof and to methods of making and using the same. The novel compounds are useful as a photoaffinity probe to study protein structure and function. Two methods for preparing 4-azidotetrafluoroaniline are disclosed, each employing a stable carbamate intermediate from which the 4-azidotetrafluoroaniline is derived.

Adolescent And Young Adult Substance Use: Association With Sensation Seeking, Self Esteem And Retrospective Report Of Early Pubertal Onset. A Preliminary Examination, Catherine A. Martin, T. K. Logan, Carl Leukefeld, Rich Milich, Hatim Omar, Richard Clayton

Psychology Faculty Publications

Structured questionnaires were administered to investigate the relationship between early pubertal onset, substance abuse, sensation seeking, and self-esteem. The current study presents data from 1,002 subjects, who were followed from the 6th to the 10th grades and again at the age of 20. In females, early pubertal onset was associated with greater cigarette use and lower self-esteem. Further the interaction of early pubertal onset and low self-esteem was predictive for cigarette use in females, as was early pubertal onset and high sensation seeking. Late pubertal onset was associated with decreased alcohol use and lower sensation seeking in males, with the …

Comparison Of The Quantification Of Caffeine In Human Plasma By Gas Chromatography And Elisa, A. B. Carregaro, W. E. Woods, Thomas Tobin, A. Queiroz-Neto

Veterinary Science Faculty Publications

In the present study we evaluated the precision of the ELISA method to quantify caffeine in human plasma and compared the results with those obtained by gas chromatography. A total of 58 samples were analyzed by gas chromatography using a nitrogen-phosphorus detector and routine techniques. For the ELISA test, the samples were diluted to obtain a concentration corresponding to 50% of the absorbance of the standard curve. To determine whether the proximity between the I₅₀ of the standard curve and that of the sample would bring about a more precise result, the samples were divided into three blocks according …

Use Of The Naturally-Occuring Quinones Thymoquinone And Dithymoquinone As Antineoplastic And Cytotoxic Agents, Peter A. Crooks, David R. Worthen, Omar A. Ghosheh

Pharmaceutical Sciences Faculty Patents

Nigella sativa derivatives, thymoquinone (TM) and dithymoquinone (DIM) are used in treatment of parental and multi-drug resistant human cancers.

Aluminium Toxicokinetics: An Updated Minireview, Robert A. Yokel, Patrick J. Mcnamara

Pharmaceutical Sciences Faculty Publications

This MiniReview updates and expands the MiniReview of aluminium toxicokinetics by Wilhelm et al. published by this journal in 1990. The use of ²⁶Al, analyzed by accelerator mass spectrometry, now enables determination of Al toxicokinetics under physiological conditions. There is concern about aluminium in drinking water. The common sources of aluminium for man are reviewed. Oral Al bioavailability from water appears to be about 0.3%. Food is the primary common source. Al bioavailability from food has not been adequately determined. Industrial and medicinal exposure, and perhaps antiperspirant use, can significantly increase absorbed aluminium. Inhalation bioavailability of airborne soluble Al …

Estrogen Protects Against The Synergistic Toxicity By Hiv Proteins, Methamphetamine And Cocaine, Jadwiga Turchan, Caroline Anderson, Kurt F. Hauser, Qinmiao Sun, Jiayou Zhang, Ying Liu, Phyllis M. Wise, Inna Kruman, William Maragos, Mark P. Mattson, Rosemarie Booze, Avindra Nath

Neurology Faculty Publications

BACKGROUND: Human immunodeficiency virus (HIV) infection continues to increase at alarming rates in drug abusers, especially in women. Drugs of abuse can cause long-lasting damage to the brain and HIV infection frequently leads to a dementing illness. To determine how these drugs interact with HIV to cause CNS damage, we used an in vitro human neuronal culture characterized for the presence of dopaminergic receptors, transporters and estrogen receptors. We determined the combined effects of dopaminergic drugs, methamphetamine, or cocaine with neurotoxic HIV proteins, gp120 and Tat.

RESULTS: Acute exposure to these substances resulted in synergistic neurotoxic responses as measured by …

Enhanced Expression Of Human Platelet-Derived Growth Factor In Pichia Pastoris, David M. Kaetzel

Pharmacology and Nutritional Sciences Faculty Patents

Enhanced yields of the platelet-derived growth factor (PDGF) B-chain are obtained using the Pichia pastoris yeast system. Yields of both wild-type and mutant human proteins are enhanced when the yeast is transformed with a vector containing the yeast mating factor promoter fused to a sequence encoding the mature protein. The secreted wild-type protein is indistinguishable from mature 29-32 kDa protein isolated from human and Chinese hamster ovary (CHO) cells. An RKK→EEE mutant exhibited reduced association with the cell surface and accumulated in the culture medium as 29-32 kDa forms. Stable transfection of U87 astrocytoma cells with RKK→EEE mutants of either …

Assessment Of Clinical Partner Violence Screening Tools, Ann L. Coker, Brian O. Pope, Paige H. Smith, Maureen Sanderson, James R. Hussey

CRVAW Faculty Journal Articles

Objective: to compare the Women’s Experience with Battering Scale (WEB) with the Index of Spouse Abuse-Physical Scale (ISA-P) as screening tools to identify intimate partner violence (IPV).

Methods: We conducted a large cross-sectional survey of women age 18 to 65 attending one of two family practice clinics from 1997 to 1998. All women completed both the WEB and the ISA-P and a telephone interview. We figured agreement estimates between the two tools, used stratified analyses to evaluate attributes of those more likely to screen as battered or physically assaulted, and compared associations between the WEB and ISA-P and a range …

Hormonal And Barrier Methods Of Contraception, Oncogenic Human Papillomaviruses, And Cervical Squamous Intraepithelial Lesion Development, Ann L. Coker, Laura C. Sanders, Sharon M. Bond, Tsilya Gerasimova, Lucia Pirisi

CRVAW Faculty Journal Articles

We assessed the influence of hormonal (oral, injectable, or levonorgestrel [Norplant, Wyeth-Ayerst, Philadelphia, PA]) and barrier methods of contraception on the risk of cervical squamous intraepithelial lesions (SIL), while adjusting for high-risk (HR) HPV infection. Subjects were women receiving family planning services through the state health department clinics from 1995 to 1998. We selected 60 cases with high-grade cervical/SIL (HSIL) and 316 with low-grade cervical/SIL (LSIL) and controls (427 women with normal cervical cytology) and analyzed cervical DNA for HR-HPV, using Hybrid Capture I (Digene; Gaithersburg, MD).When assessing ever use, duration, recency, latency, and age at first use, neither oral …

Submerged And Solid-State Phytase Fermentation By Aspergillus Niger: Effects Of Agitation And Medium Viscosity On Phytase Production, Fungal Morphology And Inoculum Performance, Maria Papagianni, Sue E. Nokes, Keith Filer

Biosystems and Agricultural Engineering Faculty Publications

Qualitative relationships between agitation levels and medium viscosity, Aspergillus niger morphology and phytase production were investigated in submerged and solid-state fermentations. Overall phytase production increased with increasing shaker speeds from 150 to 300 rpm, although specific growth rates and phytase production rates were higher at 150 rpm for 72 h from inoculation. Fungal morphology was greatly influenced by agitation with the morphological forms of small pellets and entangled mycelia predominating at 150 rpm, while the free filamentous form was obtained at 300 rpm. Upon inoculation of SSF, increased productivities were obtained from inocula grown at 150 rpm. A shift towards …

Wrist And Hand Injuries In The Athlete, Timothy L. Uhl, Philip Blazar, Greg Pitts, Kelly Ramsdell

Physical Therapy Faculty Publications

Athletes subject themselves to considerable disability. No matter the sport, the hand and upper extremity are among the most commonly injured sites. Frequently, the most debilitating complications of these conditions are the result of misdiagnosis or delayed diagnosis. Unfortunately, many patients with these delayed and misdiagnosis injuries need to be treated with surgical procedures. To compound the dilemma in treating hand and wrist injuries in this population, one needs to appreciate the athletic personality and the mentality that wishes to dismiss hand injuries as minor. It is essential to educate athletes by clearly communicating the risks and complications inherent to …

Electrolytic Lesion Of The Anterior Cingulate Cortex Decreases Inflammatory, But Not Neuropathic Nociceptive Behavior In Rats, Renee R. Donahue, Perry N. Fuchs, Stacey C. Lagraize

Renee R. Donahue

The present study investigated the effect of lesions of the anterior cingulate cortex (ACC) on mechanical allodynia / hyperalgesia after L5 ligation or on inflammatory nociceptive responses following formalin injection in the rat. For both the neuropathic and inflammatory pain models, three groups of animals were used. The control groups consisted of a group of sham lesioned animals and a group of animals that had unilateral damage to the ACC or unilateral / bilateral damage to surrounding cortical tissue. The third group consisted of animals that had at least 75% bilateral damage of the ACC. Subjects received L5 ligation or …

Enhanced Formalin Nociceptive Responses Following L5 Nerve Ligation In The Rat Reveals Neuropathy-Induced Inflammatory Hyperalgesia, Renee R. Donahue, Perry N. Fuchs

Renee R. Donahue

The development of mechanical and thermal hypersensitivity following peripheral nerve injury is well known and a great deal of research has been directed towards understanding the mechanisms underlying these phenomena. However, there has been very little research examining if hypersensitivity to an inflammatory condition following nerve injury also develops. Therefore, the purpose of the present study was to determine if hypersensitivity to an inflammatory condition produced in the formalin test develops following ligation of the L5 spinal nerve. Male Sprague–Dawley rats received tight ligation of the L5 spinal nerve or were given sham surgery. Following a 14-day recovery period, the …

Clenbuterol In The Horse: Confirmation And Quantitation Of Serum Clenbuterol By Lc-Ms-Ms After Oral And Intratracheal Administration, A. F. Lehner, J Daniel Harkins, W. Karpiesiuk, W. E. Woods, N. E. Robinson, L. Dirikolu, M. Fisher, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Clenbuterol is a β₂ agonist/antagonist bronchodilator, and its identification in post-race samples may lead to sanctions. The objective of this study was to develop a specific and highly sensitive serum quantitation method for clenbuterol that would allow effective regulatory control of this agent in horses. Therefore, clenbuterol-d₉ was synthesized for use as an internal standard, an automated solid-phase extraction method was developed, and both were used in conjunction with a multiple reaction monitoring liquid chromatography-tandem mass spectrometry (LC-MS-MS) method to allow unequivocal identification and quantitation of clenbuterol in 2 mL of serum at concentrations as low as 10 …

The Translational Regulation Of Lipoprotein Lipase In Diabetic Rats Involves The 3′-Untranslated Region Of The Lipoprotein Lipase Mrna, Gouri Ranganathan, Chunling Li, Philip A. Kern

Clinical and Translational Science Faculty Publications

Adipose tissue lipoprotein lipase (LPL) activity is decreased in patients with poorly controlled diabetes, and this contributes to the dyslipidemia of diabetes. To study the mechanism of this decrease in LPL, we studied adipose tissue LPL expression in male rats with streptozotocin-induced diabetes. Heparin releasable and extractable LPL activity in the epididymal fat decreased by 75-80% in the diabetic group and treatment of the rats with insulin prior to sacrifice reversed this effect. Northern blot analysis indicated no corresponding change in LPL mRNA levels. However, LPL synthetic rate, measured using [³⁵S]methionine pulse labeling, was decreased by 75% in …

Phosphonated Agents And Their Antiangiogenic And Antitumorigenic Use, Delwood C. Collins, Antonio Gagliardi, Peter Nickel

Obstetrics and Genecology Faculty Patents

Phosphonic acid agents are synthesized and characterized which are potent inhibitors of angiogenesis, tumorigenesis and metalloproteinase activity. Their method of use for the inhibition of angiogenesis and metalloproteinase and the treatment of tumors is also shown.

Combined Antagonist Compositions, Scott R. Hamann

Anesthesiology Faculty Patents

Novel compositions of a combination of nicotinic, opioid, serotonergic and/or adrenergic antagonists in combination with nicotinic and opioid agonists, anti-depressants, stimulants, non-steroidal anti-inflammatory drugs, and local anesthetics, such combinations being useful in the treatment of excitable system disorders, pain and psychiatric disorders, and methods of use thereof.

Estrogen-Induced Relaxation In Bovine Coronary Arteries In Vitro: Evidence For A New Mechanism, Jelica D. J. Kalenic, Rolando J. Ramirez, Stanley Einzig, William A. Neal, Hatim A. Omar

Pediatrics Faculty Publications

Numerous studies have shown estrogen to be vasoactive in various circulations. Our objective was to determine the effect of estrogen on isolated bovine coronary arteries and the possible mechanism. Bovine coronary arteries, precontracted with thromboxane mimetic U₄₆₆₁₉ were given doses (0.01-30μM) of 17Β-estradiol in the presence and absence of endothelium and these inhibitors: 10μM indomethacin (cyclooxygenase inhibitor), 10μM methylene blue (inhibits soluble guanylate cyclase), 100μM nitro-L-arginine (inhibits nitric oxide synthesis), 100μM isobutylmethylxanthine (phosphodiesterase inhibitor) and 30μM mifepristone (Ru₃₈₄₈₆ steroid receptor antagonist). Our results indicated that, estrogen, in the highest concentration used (30μM), elicited an acute dose-dependent relaxation of …

The Toxicology Of Aluminum In The Brain: A Review, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Aluminum is environmentally ubiquitous, providing human exposure. Usual human exposure is primarily dietary. The potential for significant Al absorption from the nasal cavity and direct distribution into the brain should be further investigated. Decreased renal function increases human risk of Al-induced accumulation and toxicity. Brain Al entry from blood may involve transferrin-receptor mediated endocytosis and a more rapid process transporting small molecular weight Al species. There appears to be Al efflux from the brain, probably as Al citrate. There is prolonged retention of a fraction of Al that enters the brain, suggesting the potential for accumulation with repeated exposure. Al …

Combination Anti-Leukimic Therapy By Utilizing Suramin And Biologic Response Modifiers, Michael A. Doukas

Internal Medicine Faculty Patents

A method of treating leukemia which includes administering an effective amount of composition comprising suramin and a biological response modifier, wherein the suramin and the biological response modifier show synergistic or additive anti-leukemic activity. A pharmaceutical composition is also disclosed.

Sarcocystis Neurona Diagnostic Primer And Its Use In Methods Of Equine Protozoal Myeloencephalitis Diagnosis, Clara K. Fenger, David E. Granstrom, Alvin A. Gajadhar, Jitender P. Dubey

Veterinary Science Faculty Patents

An amplification primer and probe which can be used in an in vitro diagnostic test for the presence of S. neurona in equine blood or cerebrospinal fluid. Sarcocystis neurona is responsible for the equine condition of protozoal myelitis. The amplification primer is seventeen nucleotides in length and complementary to a unique section of the small ribosomal subunit of Sarcocystis neurona. The primer encompasses nucleotide positions 1470-1487 of the small ribosomal subunit of S. neurona. The primer has the sequence 5' CCATTCCGGACGCGGGT SEQ ID NO:1.