Medicine and Health Sciences Commons^™

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 …

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 …

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 …

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 …

Accessory Cell Defect In Unresponsiveness Of Neonates And Aged To Polysaccharide Vaccines., Subbarao Bondada, H Wu, D A Robertson, R L Chelvarajan

Microbiology, Immunology, and Molecular Genetics Faculty Publications

T independent antigens elicit antibody responses in the absence of carrier specific T helper cells but require signals from accessory cells (macrophages and dendritic cells) or specific cytokines. They are further subdivided into TI-1 and TI-2 categories based on the ability of TI-1 but not TI-2 antigens to elicit immune responses from neonates. Most bacterial polysaccharides including the pneumococcal polysaccharide vaccines belong to the TI-2 class. It is hypothesized that defects in accessory cell function play a critical role in the failure of neonates to respond to such TI-2 antigens. Immune responses to these TI-2 stimuli are also reduced in …

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.

Method Of Treatment Of Conditions Associate With Oxidative Tissue Damage, 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, …

Pathogen-Inducible Regulatory Element, Joseph Chappell, Catherine A. G. Cornett, Shauhui Yui

Pharmaceutical Sciences Faculty Patents

Qualitative transcriptional regulatory sequences functional in plants, plant tissue and in plant cells for inducible gene expression and quantitative transcriptional regulatory sequences for increasing the transcriptional expression of downstream genetic information in plants, plant tissue and plant cells are disclosed. Also disclosed are methods and recombinant DNA molecules for improving the disease resistance of transgenic plants, especially wherein an inducible promoter controls the expression of a protein capable of evoking the hypersensitive response in a plant.

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.

Use Of Lobeline Compounds In The Treatment Of Central Nervous System Diseases And Pathologies, Peter A. Crooks, Linda P. Dwoskin

Pharmaceutical Sciences Faculty Patents

Lobeline and nicotine evoke [³H]overflow from rat striatal slices preloaded with [³H]dopamine ([³H]DA). The lobeline-evoked overflow is calcium-independent and not antagonized by mecamylamine, suggesting a mechanism of action other than the stimulation of nicotinic receptors. Whereas nicotine stimulates nicotinic receptors, lobeline inhibits [³H]DA uptake into synaptic vesicles and striatal synaptosomes. The results suggest that different mechanisms are responsible for the increase in striatal DA release evoked by lobeline and nicotine. [³H]-Dihydrotetrabenazine [³H]DTBZ), used routinely to probe a high-affinity binding site-on the vesicular monoamine transporter (VMAT2) binds to vesicle …

Fatal Injuries Due To Logs Rolling Off Trucks At Sawmills, Kentucky Injury Prevention And Research Center

Kentucky Haz Alerts--Tractors/Logging

Logging is one of the most hazardous occupations in the nation as well as Kentucky. During 1994-1998, 45 fatalities in Kentucky were related to logging. Of those deaths, 7 were due to logs rolling off trucks at sawmills. The workers were all males and aged 31-64 years. Their experience varied from less than 1 year to more than 25 years. Below are brief case reports of three fatal events, followed by recommendations for prevention of similar events.