Medicine and Health Sciences Commons^™

Chelating Compounds And Immobilized Tethered Chelators, Robert A. Yokel, Wesley R. Harris, Christopher D. Spilling, Chang-Guo Zhan

Pharmaceutical Sciences Faculty Patents

Novel di- and tripodal compounds useful as chelators, intermediates for their production and a method for treating an aqueous solution to remove trivalent metal ions are presented.

Semi Truck Driver Falls Asleep While Driving, Crashes And Dies, Kentucky Injury Prevention And Research Center

Fatality Case Reports--Motor Vehicle

A 56 year-old male long-haul semi-truck driver fell asleep while driving. It was approximately 4:15 AM and the driver was hauling a load of canned tomatoes. He was approximately 225 miles away from his destination driving in the right hand lane, on a four lane interstate traveling south, when he fell asleep. Upon falling asleep, the unit travelled to the right, across the rumble strip and the emergency lane, behind a guardrail, down an embankment and crashed into a grove of trees. A man driving a car behind the semi truck saw dust rise from the crash, stopped, called emergency …

Methods And Animal Model For Analyzing Age-Related Macular Degeneration, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Patents

Methods for testing candidate drugs for treatment of age-related macular degeneration are provided. Ccl2-deficient, and Ccr2-deficient mice are used to determine the effect of candidate drugs and treatments on development of age-related macular degeneration. Also provided is a Ccl2-deficient, Ccr2-deficient dual knockout mouse, which is a useful animal model for age-related macular degeneration.

Oxidative Stress Accumulates In Adipose Tissue During Aging And Inhibits Adipogenesis, Hannes M. Findeisen, Kevin J. Pearson, Florence Gizard, Yue Zhao, Hua Qing, Karrie L Jones, Dianne Cohn, Elizabeth B. Heywood, Rafael De Cabo, Dennis Bruemmer

Saha Cardiovascular Research Center Faculty Publications

Aging constitutes a major independent risk factor for the development of type 2 diabetes and is accompanied by insulin resistance and adipose tissue dysfunction. One of the most important factors implicitly linked to aging and age-related chronic diseases is the accumulation of oxidative stress. However, the effect of increased oxidative stress on adipose tissue biology remains elusive. In this study, we demonstrate that aging in mice results in a loss of fat mass and the accumulation of oxidative stress in adipose tissue. In vitro, increased oxidative stress through glutathione depletion inhibits preadipocyte differentiation. This inhibition of adipogenesis is at …

Does Comorbidity Explain The Ethnic Inequalities In Cervical Cancer Survival In New Zealand? A Retrospective Cohort Study, Naomi Brewer, Barry Borman, Diana Sarfati, Mona Jeffreys, Steven T. Fleming, Soo Cheng, Neil Pearce

Epidemiology and Environmental Health Faculty Publications

BACKGROUND: There are large ethnic differences in cervical cancer survival in New Zealand that are only partly explained by stage at diagnosis. We investigated the association of comorbidity with cervical cancer survival, and whether comorbidity accounted for the previously observed ethnic differences in survival.

METHODS: The study involved 1,594 cervical cancer cases registered during 1994-2005. Comorbidity was measured using hospital events data and was classified using the Elixhauser instrument; effects on survival of individual comorbid conditions from the Elixhauser instrument were also assessed. Cox regression was used to estimate adjusted cervical cancer mortality hazard ratios (HRs).

RESULTS: Comorbidity during the …

Expression Stability Of Putative Reference Genes In Equine Endometrial, Testicular, And Conceptus Tissues, Claudia Klein, Josep Rutllant, Mats H. T. Troedsson

Veterinary Science Faculty Publications

BACKGROUND: Quantitative RT-PCR data are commonly normalized using a reference gene. A reference gene is a transcript which expression does not differ in the tissue of interest independent of the experimental condition. The objective of this study was to evaluate the stability of mRNA expression levels of putative reference genes in three different types of equine tissue, endometrial, testicular, and conceptus tissue.

FINDINGS: The expression stability of four (uterine tissue) and six (testicular and conceptus tissue) was assessed using descriptive data analysis and the software programs Normfinder and geNorm. In uterine samples, 18S showed the largest degree of variation in …

Phenethyl Isothiocyanate Exhibits Antileukemic Activity In Vitro And In Vivo By Inactivation Of Akt And Activation Of Jnk Pathways, N. Gao, Amit Budhraja, S. Cheng, E.-H. Liu, J. Chen, Z. Yang, D. Chen, Zhuo Zhang, Xianglin Shi

Toxicology and Cancer Biology Faculty Publications

Effects of phenethyl isothiocyanate (PEITC) have been investigated in human leukemia cells (U937, Jurkat, and HL-60) as well as in primary human acute myeloid leukemia (AML) cells in relation to apoptosis and cell signaling events. Exposure of cells to PEITC resulted in pronounced increase in the activation of caspase-3, -8, -9, cleavage/degradation of PARP, and apoptosis in dose- and time-dependent manners. These events were accompanied by the caspase-independent downregulation of Mcl-1, inactivation of Akt, as well as activation of Jun N-terminal kinase (JNK). Inhibition of PI3K/Akt by LY294002 significantly enhanced PEITC-induced apoptosis. Conversely, enforced activation of Akt by a constitutively …

Nanotubes As Mitochondrial Uncouplers, Patrick G. Sullivan

Neuroscience Faculty Patents

A method of uncoupling mitochondria in a subject including administering nanotubes to the subject in a therapeutically effective amount, wherein the nanotubes are self-rectifying is provided. A method of decreasing reactive oxygen species and decreasing detrimental loading of Ca²⁺ into mitochondria is provided, including administering a pharmaceutically effective amount of nanotubes into the subject. A method of reducing weight, treating cancer, reducing the effects of traumatic brain injury, or reducing the effects of ageing, in a subject including administering a pharmaceutically effective amount of nanotubes into the subject is also provided.

High-Activity Mutants Of Butyrylcholinesterase For Cocaine Hydrolysis And Method Of Generating The Same, Chang-Guo Zhan, Hoon Cho, Hsin-Hsiung Tai

Pharmaceutical Sciences Faculty Patents

A novel computational method and generation of mutant butyrylcholinesterase for cocaine hydrolysis is provided. The method includes molecular modeling a possible BChE mutant and conducting molecular dynamics simulations and hybrid quantum mechanical/molecular mechanical calculations thereby providing a screening method of possible BChE mutants by predicting which mutant will lead to a more stable transition state for a rate determining step. Site-directed mutagenesis, protein expression, and protein activity is conducted for mutants determined computationally as being good candidates for possible BChE mutants, i.e., ones predicted to have higher catalytic efficiency as compared with wild-type BChE. In addition, mutants A199S/A328W/Y332G, A199S/F227A/A328W/Y332G, A199S/S287G/A328W/Y332G, …

Obesity And Hepatosteatosis In Mice With Enhanced Oxidative Dna Damage Processing In Mitochondria, Haihong Zhang, Chenghui Xie, Horace J. Spencer, Chunlai Zuo, Masahiro Higuchi, Gouri Ranganathan, Philip A. Kern, Ming W. Chou, Qin Huang, Bartosz Szczesny, Sankar Mitra, Amanda J. Watson, Geoffrey P. Margison, Chun-Yang Fan

Clinical and Translational Science Faculty Publications

Mitochondria play critical roles in oxidative phosphorylation and energy metabolism. Increasing evidence supports that mitochondrial DNA (mtDNA) damage and dysfunction play vital roles in the development of many mitochondria-related diseases, such as obesity, diabetes mellitus, infertility, neurodegenerative disorders, and malignant tumors in humans. Human 8-oxoguanine-DNA glycosylase 1 (hOGG1) transgenic (TG) mice were produced by nuclear microinjection. Transgene integration was analyzed by PCR. Transgene expression was measured by RT-PCR and Western blot analysis. Mitochondrial DNA damage was analyzed by mutational analyses and measurement of mtDNA copy number. Total fat content was measured by a whole-body scan using dual-energy X-ray absorptiometry. The …

Transylvania Medical Alumni Served Both Sides During The Civil War, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

No abstract provided.

A Transylvania Medical Graduate Searches For His Sons After A Civil War Battle, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

No abstract provided.

Response To An Abnormal Ovarian Cancer-Screening Test Result: Test Of The Social Cognitive Processing And Cognitive Social Health Information Processing Models, Michael A. Andrykowski, Edward J. Pavlik

Behavioral Science Faculty Publications

All cancer screening tests produce a proportion of abnormal results requiring follow up. Consequently, the cancer-screening setting is a natural laboratory for examining psychological and behavioural response to a threatening health-related event. This study tested hypotheses derived from the social cognitive processing and cognitive-social health information processing models in trying to understand response to an abnormal ovarian cancer (OC) screening test result. Women (n = 278) receiving an abnormal screening test result a mean of 7 weeks earlier were assessed prior to a repeat screening test intended to clarify their previous abnormal result. Measures of disposition (optimism, informational coping style), …

P53 Regulates Oxidative Stress-Mediated Retrograde Signaling: A Novel Mechanism For Chemotherapy-Induced Cardiac Injury, Joyce M. Velez, Sumitra Miriyala, Ramaneeya Nithipongvanitch, Teresa Noel, Chotiros D. Plabplueng, Terry Oberley, Paiboon Jungsuwadee, Holly Van Remmen, Mary Vore, Daret K. St Clair

Toxicology and Cancer Biology Faculty Publications

The side effects of cancer therapy on normal tissues limit the success of therapy. Generation of reactive oxygen species (ROS) has been implicated for numerous chemotherapeutic agents including doxorubicin (DOX), a potent cancer chemotherapeutic drug. The production of ROS by DOX has been linked to DNA damage, nuclear translocation of p53, and mitochondrial injury; however, the causal relationship and molecular mechanisms underlying these events are unknown. The present study used wild-type (WT) and p53 homozygous knock-out (p53(-/-)) mice to investigate the role of p53 in the crosstalk between mitochondria and nucleus. Injecting mice with DOX (20 mg/kg) causes oxidative stress …

Differential Levels Of Glutamate Dehydrogenase 1 (Glud1) In Balb/C And C57bl/6 Mice And The Effects Of Overexpression Of The Glud1 Gene On Glutamate Release In Striatum, Kevin N. Hascup, Xiaodong Bao, Erin R. Hascup, Dongwei Hui, Wenhao Xu, Francois Pomerleau, Peter Huettl, Mary L. Michaelis, Elias K. Michaelis, Greg A. Gerhardt

Neuroscience Faculty Publications

We have previously shown that overexpression of the Glud1 (glutamate dehydrogenase 1) gene in neurons of C57BL/6 mice results in increased depolarization-induced glutamate release that eventually leads to selective neuronal injury and cell loss by 12 months of age. However, it is known that isogenic lines of Tg (transgenic) mice produced through back-crossing with one strain may differ in their phenotypic characteristics from those produced using another inbred mouse strain. Therefore, we decided to introduce the Glud1 transgene into the Balb/c strain that has endogenously lower levels of GLUD1 (glutamate dehydrogenase 1) enzyme activity in the brain as compared with …

In Vitro Amplification Of Misfolded Prion Protein Using Lysate Of Cultured Cells, Charles E. Mays, Jihyun Yeom, Hae-Eun Kang, Jifeng Bian, Vadim Khaychuk, Younghwan Kim, Jason C Bartz, Glenn C Telling, Chongsuk Ryou

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Protein misfolding cyclic amplification (PMCA) recapitulates the prion protein (PrP) conversion process under cell-free conditions. PMCA was initially established with brain material and then with further simplified constituents such as partially purified and recombinant PrP. However, availability of brain material from some species or brain material from animals with certain mutations or polymorphisms within the PrP gene is often limited. Moreover, preparation of native PrP from mammalian cells and tissues, as well as recombinant PrP from bacterial cells, involves time-consuming purification steps. To establish a convenient and versatile PMCA procedure unrestricted to the availability of substrate sources, we attempted to …

Engineered Nanomaterials: Exposures, Hazards, And Risk Prevention, Robert A. Yokel, Robert C. Macphail

Pharmaceutical Sciences Faculty Publications

Nanotechnology presents the possibility of revolutionizing many aspects of our lives. People in many settings (academic, small and large industrial, and the general public in industrialized nations) are either developing or using engineered nanomaterials (ENMs) or ENM-containing products. However, our understanding of the occupational, health and safety aspects of ENMs is still in its formative stage. A survey of the literature indicates the available information is incomplete, many of the early findings have not been independently verified, and some may have been over-interpreted. This review describes ENMs briefly, their application, the ENM workforce, the major routes of human exposure, some …

Safety And Tolerability Of An Ovine-Derived Polyclonal Anti-Tnfα Fab Fragment (Azd9773) In Patients With Severe Sepsis, Peter E. Morris, Brian Zeno, Andrew C. Bernard, Xiangning Huang, Steven G. Simonson, Gordon R. Bernard

Surgery Presentations

Sepsis remains a significant medical problem. TNFα is a central cytokine in sepsis pathophysiology. We conducted a phase IIa trial in patients with severe sepsis to assess the safety and tolerability of an intravenously infused ovine-derived polyclonal anti-TNFα Fab fragment (AZD9773).

The Role Of Xpg In Processing (Cag)N/(Ctg)N Dna Hairpins, Caixia Hou, Tianyi Zhang, Lei Tian, Jian Huang, Liya Gu, Guo-Min Li

Toxicology and Cancer Biology Faculty Publications

BACKGROUND: During DNA replication or repair, disease-associated (CAG)n/(CTG)n expansion can result from formation of hairpin structures in the repeat tract of the newly synthesized or nicked DNA strand. Recent studies identified a nick-directed (CAG)n/(CTG)n hairpin repair (HPR) system that removes (CAG)n/(CTG)n hairpins from human cells via endonucleolytic incisions. Because the process is highly similar to the mechanism by which XPG and XPF endonucleases remove bulky DNA lesions during nucleotide excision repair, we assessed the potential role of XPG in conducting (CAG)n/(CTG)n HPR.

RESULTS: To determine if the XPG endonuclease is involved in (CAG)n/(CTG)n hairpin removal, two XPG-deficient cell lines (GM16024 …

Racial/Ethnic Disparities In Survival Among Men Diagnosed With Prostate Cancer In Texas, Arica L. White, Ann L. Coker, Xianglin L. Du, Katherine S. Eggleston, Melanie Williams

CRVAW Faculty Journal Articles

BACKGROUND:

To the authors' knowledge, few studies to date have examined racial differences in prostate cancer survival while controlling for socioeconomic status (SES). No such studies have examined this association in Texas, a large state with significant ethnic and racial diversity. The objective of this analysis was to determine whether racial disparities in survival for men diagnosed with prostate cancer in Texas from 1995 through 2002 remained after adjusting for SES, rural residence, and stage of disease.

METHODS:

A cohort of 87,449 men who were diagnosed with prostate cancer was identified from the Texas Cancer Registry. The SES measure was …

Semi Drivers Killed After Vehicle Rollovers, Kentucky Injury Prevention And Research Center

Kentucky Haz Alerts--Motor Vehicle

To prevent semi truck rollovers, employers should:

• Implement and enforce a seat belt safety program
• Establish and strengthen a company policy to reduce fatigue on the job

Employees should:

• Always wear a seat belt while in the vehicle
• Use correct lights during a fog
• Use proper precautions to reduce sloshing
• Reduce inadequate evasive actions

Global Gene Expression Profiles Of Subcutaneous Adipose And Muscle From Glucose-Tolerant, Insulin-Sensitive, And Insulin-Resistant Individuals Matched For Bmi, Steven C. Elbein, Philip A. Kern, Neda Rasouli, Aiwei Yao-Borengasser, Neeraj K. Sharma, Swapan K. Das

Clinical and Translational Science Faculty Publications

OBJECTIVE - To determine altered gene expression profiles in subcutaneous adipose and skeletal muscle from nondiabetic, insulin-resistant individuals compared with insulin-sensitive individuals matched for BMI.

RESEARCH DESIGN AND METHODS - A total of 62 nondiabetic individuals were chosen for extremes of insulin sensitivity (31 insulin-resistant and 31 insulin-sensitive subjects; 40 were European American and 22 were African American) and matched for age and obesity measures. Global gene expression profiles were determined and compared between ethnic groups and between insulin-resistant and insulin-sensitive participants individually and using gene-set enrichment analysis.

RESULTS - African American and European American subjects differed in 58 muscle …

Menstrual Bleeding Patterns In Adolescents Using Etonogestrel (Eng) Implant, Amit M. Deokar, Wendy Jackson, Hatim A. Omar

Pediatrics Faculty Publications

Background: Etonogestrel (ENG) implant is an effective method of contraception. The implant is designed to provide contraceptive efficacy for 3 years with a relatively quick return of fertility upon its removal. Menstrual irregularities are not uncommon on long-acting progestins and can often be the factor for discontinuation or removal. A retrospective chart analysis was done on 58 patients who chose to be on the ENG implant. Age ranged from 12 to 24 years. The cycle ranged from 1 to 17 months. The mean length of use of the implant was 10.9 months. Over the 20-month period, 13 ENG implants were …

High Activity Mutants Of Butyrylcholinesterase For Cocaine Hydrolysis, Chang-Guo Zhan, Fang Zheng, Wenchao Yang

Pharmaceutical Sciences Faculty Patents

Butyrylcholinesterase (BChE) polypeptide variants of the presently-disclosed subject matter have enhanced catalytic efficiency for (−)-cocaine, as compared to wild-type BChE. Pharmaceutical compositions of the presently-disclosed subject matter include a BChE polypeptide variant having an enhanced catalytic efficiency for (−)-cocaine. A method of the presently-disclosed subject matter for treating a cocaine-induced condition includes administering to an individual an effective amount of a BChE polypeptide variant, as disclosed herein, to lower blood cocaine concentration.

A Brief History Of Phssr: The National Coordinating Center. Lessons From History, F. Douglas Scutchfield Md

Preventive Medicine and Environmental Health Presentations

No abstract provided.

Aspirin Treatment Of Mice Infected With Trypanosoma Cruzi And Implications For The Pathogenesis Of Chagas Disease, Shankar Mukherjee, Fabiana S. Machado, Huang Huang, Helieh S. Oz, Linda A. Jelicks, Cibele M. Prado, Wade Koba, Eugene J. Fine, Dazhi Zhao, Stephen M. Factor, J. Elias Collado, Louis M. Weiss, Herbert B. Tanowitz, Anthony W. Ashton

Center for Oral Health Research Faculty Publications

Chagas disease, caused by infection with Trypanosoma cruzi, is an important cause of cardiovascular disease. It is increasingly clear that parasite-derived prostaglandins potently modulate host response and disease progression. Here, we report that treatment of experimental T. cruzi infection (Brazil strain) beginning 5 days post infection (dpi) with aspirin (ASA) increased mortality (2-fold) and parasitemia (12-fold). However, there were no differences regarding histopathology or cardiac structure or function. Delayed treatment with ASA (20 mg/kg) beginning 60 dpi did not increase parasitemia or mortality but improved ejection fraction. ASA treatment diminished the profile of parasite- and host-derived circulating prostaglandins in infected …

Evaluation Of Immune Responses Following Infection Of Ponies With An Ehv-1 Orf1/2 Deletion Mutant, Gisela Soboll Hussey, Stephen B. Hussey, Bettina Wagner, David W. Horohov, Gerlinde R. Van De Walle, Nikolaus Osterrieder, Lutz S. Goehring, Sangeeta Rao, David P. Lunn

Veterinary Science Faculty Publications

Equine herpesvirus-1 (EHV-1) infection remains a significant problem despite the widespread use of vaccines. The inability to generate a protective immune response to EHV-1 vaccination or infection is thought to be due to immunomodulatory properties of the virus, and the ORF1 and ORF2 gene products have been hypothesized as potential candidates with immunoregulatory properties. A pony infection study was performed to define immune responses to EHV-1, and to determine if an EHV-1 ORF1/2 deletion mutant (ΔORF1/2) would have different disease and immunoregulatory effects compared to wild type EHV-1 (WT). Infection with either virus led to cytokine responses that coincided with …

Subjects With Discordant Airways Obstruction: Lost Between Spirometric Definitions Of Copd, Bernd Lamprecht, Lea Schirnhofer, Bernhard Kaiser, Sonia A. Buist, David Mannino, Michael Studnicka

Preventive Medicine and Environmental Health Faculty Publications

Background. Since the FEV1/FVC ratio declines with age, using the fixed ratio of 0.70 leads to overdiagnosis of COPD in older populations and underdiagnosis among young adults. Objective. To evaluate whether discordant obstructive cases (FEV1/FVC < 0.70 but ≥LLN) are a healthy population or have clinical features that would place them at increased risk. Methods. We used post-bronchodilator spirometry data from the population-based Austrian Burden of Obstructive Lung Disease (BOLD) study. Those with post-bronchodilator FEV1/FVC ratio

Pediatric Ethics Guidelines For Hereditary Medullary Thyroid Cancer, M. Sara Rosenthal, Douglas S. Diekema

Internal Medicine Faculty Publications

Hereditary medullary thyroid cancer is an aggressive cancer for which there is no standard effective systemic therapy, but which can be prevented through genetic screening and prophylactic thyroidectomy. Although this cancer accounts for roughly 17% of all pediatric thyroid cancers, a significant percentage of affected families do not "accept" screening, while many gene carriers delay or refuse prophylactic thyroid surgery for their children. Current genetic screening practices in medullary thyroid cancer are inadequate; more than 50% of index patients with hereditary medullary thyroid cancer present with a thyroid mass; up to 75% have distant metastasis. These proposed pediatric ethics guidelines …

Cmr Of Lv Non-Compaction Cardiomyopathy: Association Of Clinical Presentation And Prognosis With Cardiac Phenotype, Mushabbar A. Syed, Steve W. Leung, Samy Claude Elayi, Richard J. Charnigo

Internal Medicine Presentations

Left ventricular non-compaction (LVNC) is a rare congenital disorder characterized by two layered myocardium; trabeculated (non-compacted) and a non-trabeculated (compacted). LVNC is increasingly being recognized due to better imaging technology as a cause for heart failure and sudden cardiac death; however, data on clinical and imaging characteristics remains limited.