Medicine and Health Sciences Commons^™

Biochemical Characterization Of Human Mismatch Recognition Proteins Mutsα And Mutsβ, Lei Tian

University of Kentucky Doctoral Dissertations

The integrity of an organism's genome depends on the fidelity of DNA replication and the efficiency of DNA repair. The DNA mismatch repair (MMR) system, which is highly conserved from prokaryotes to eukaryotes, plays an important role in maintaining genome stability by correcting base-base mismatches and insertion/deletion (ID) mispairs generated during DNA replication and other DNA transactions. Mismatch recognition is a critical step in MMR. Two mismatch recognition proteins, MutSα (MSH2-MSH6 heterodimer) and MutSβ (MSH2-MSH3 heterodimer), have been identified in eukaryotic cells. MutSα and MutSβ have partially overlapping functions, with MutSα recognizing primarily base-base mismatches and 1-2 nt ID mispairs …

Explorations In Homeoviscous Adaptation And Mass Spectral Analysis Of Membrane Lipids, Michael Douglas Timmons

University of Kentucky Doctoral Dissertations

The focus of this dissertation is centered on the mass spectral analysis of lipids and changes occurring in keeping with the concept of homeoviscous adaptation [1]. Homeoviscous adaptation is the process of modification of membrane lipids in response to environmental stimuli [1]. Dissertation investigations applied this concept to prokaryotic and eukaryotic organisms, and expanded the perception of environmental factors from exogenous organic solvents to intracellular environment.

The field of lipidomics deals with the analysis of phospholipid and fatty acid components of membranes the changes that occur due to environmental stimuli and their biological significance [2-6]. The high sensitivity of mass …

Prognostic Significance Of Trail Death Receptors In Middle Eastern Colorectal Carcinomas And Their Correlation To Oncogenic Kras Alterations, Prashant Bavi, Sarita E Prabhakaran, Jehad Abubaker, Zeeshan Qadri, Thara George, Nasser Al-Sanea, Alaa Abduljabbar, Luai H Ashari, Samar Alhomoud, Fouad Al-Dayel, Azhar Hussain, Shahabuddin, Khawla S Al-Kuraya

Centre for Regenerative Medicine & Stem Cell Research

Background: Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumour necrosis factor cytokine family that induces apoptosis upon binding to its death domain containing receptors, TRAIL receptor 1 (DR4) and TRAIL receptor 2 (DR5). Expression of TRAIL receptors is higher in colorectal carcinoma (CRC) as compared to normal colorectal mucosa and targeted therapy with TRAIL leads to preferential killing of tumor cells sparing normal cells.
Methods: We investigated the expression of TRAIL and its receptors in a tissue microarray cohort of 448 Middle Eastern CRC. We also studied the correlation between TRAIL receptors and various clinico-pathological …

Letter To The Editor: Reproductive Toxicology, Robert L. Brent

The Selected Works of Robert Brent

No abstract provided.

What Are The Reproductive And Developmental Risks Of Ionizing Radiation?, Robert L. Brent Dr.

The Selected Works of Robert Brent

None

Differential Impact Of Tumor Suppressor Pathways On Dna Damage Response And Therapy-Induced Transformation In A Mouse Primary Cell Model., A Kathleen Mcclendon, Jeffry L Dean, Adam Ertel, Erik S Knudsen

Department of Cancer Biology Faculty Papers

The RB and p53 tumor suppressors are mediators of DNA damage response, and compound inactivation of RB and p53 is a common occurrence in human cancers. Surprisingly, their cooperation in DNA damage signaling in relation to tumorigenesis and therapeutic response remains enigmatic. In the context of individuals with heritable retinoblastoma, there is a predilection for secondary tumor development, which has been associated with the use of radiation-therapy to treat the primary tumor. Furthermore, while germline mutations of the p53 gene are critical drivers for cancer predisposition syndromes, it is postulated that extrinsic stresses play a major role in promoting varying …

Reduced Hamster Usage And Stress In Propagating Leishmania Chagasi Promastigotes Using Cryopreservation And Saphenous Vein Inoculation, Soi Meng Lei, Amanda E. Ramer-Tait, Rebecca R. Dahlin-Laborde, Kathleen Mullin, Jeffrey K. Beetham

Amanda Ramer-Tait Publications

Leishmania chagasi, a causal agent of visceral leishmaniasis, requires passage through lab animals such as hamsters to maintain its virulence. Hamster infection is typically accomplished via cardiac puncture or intraperitoneal injection, procedures accompanied by risks of increased animal stress and death. The use of the hamster model also necessitates a regular supply of infected animals, because L. chagasi parasites newly isolated from an infected hamster can be grown in culture for only several weeks before loss of function/phenotype occurs. In an effort to decrease animal usage and animal stress, experiments were performed to assess a more gentle inoculation …

Individuality In Gut Microbiota Composition Is A Complex Polygenic Trait Shaped By Multiple Environmental And Host Genetic Factors, Andrew K. Benson, Scott A. Kelly, Ryan Legge, Fangrui Ma, Soo Jen Low, Jaehyoung Kim, Min Zhang, Phaik Lyn Oh, Derrick Nehrenberg, Kunjie Huab, Stephen D. Kachman, Etsuko N. Moriyama, Jens Walter, Daniel A. Peterson, Daniel Pomp

Center for Plant Science Innovation: Faculty Publications

In vertebrates, including humans, individuals harbor gut microbial communities whose species composition and relative proportions of dominant microbial groups are tremendously varied. Although external and stochastic factors clearly contribute to the individuality of the microbiota, the fundamental principles dictating how environmental factors and host genetic factors combine to shape this complex ecosystem are largely unknown and require systematic study. Here we examined factors that affect microbiota composition in a large (n = 645) mouse advanced intercross line originating from a cross between C57BL/6J and an ICR-derived outbred line (HR). Quantitative pyrosequencing of the microbiota defined a core measurable microbiota …

Effect Of Dietary Folate Restriction On Colon Carcinogenesis In Dna Polymerase Β Haploinsufficient Mice, Lisa F. Ventrella Lucente

Wayne State University Dissertations

The data presented in this research is central to establishing the role that the base excision repair pathway (BER) plays in the development and progression of colon cancer when dietary folate is deficient. Both cellular folate restriction and BER deficiencies have been shown to result in the accumulation of endogenous damage and lesions that could eventually develop into carcinogenesis. In this study, a dietary folate deficiency (FD) resulted in a significant increase in aberrant crypt foci (ACF) formation and triggered liver tumorogenesis in wildtype (WT) animals, as did a BER deficiency in DNA polymerase Β haploinsufficient (Β-pol+/-) mice exposed to …

Role Of Transforming Growth Factor Beta In Corneal Function, Biology And Pathology, Ashish Tandon, Jonathan C. K. Tovey, Ajay Sharma, Rangan Gupta, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Transforming growth factor-beta (TGFβ) is a pleiotropic multifunctional cytokine that regulates several essential cellular processes in many parts of the body including the cornea. Three isoforms of TGFβ are known in mammals and the human cornea expresses all of them. TGFβ1 has been shown to play a central role in scar formation in adult corneas whereas TGFβ2 and TGFβ3 have been implicated to play a critical role in corneal development and scarless wound healing during embryogenesis. The biological effects of TGFβ in the cornea have been shown to follow SMAD dependent as well as SMAD-independent signaling pathways depending upon cellular …

Gene Delivery In The Equine Cornea: A Novel Therapeutic Strategy, Dylan G. Buss, Ajay Sharma, Elizabeth A. Giuliano, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Objective—To determine if hybrid adeno-associated virus serotype 2/5 (AAV5) vector can effectively deliver foreign genes into the equine cornea without causing adverse side effects. The aims of this study were to: (i) evaluate efficacy of AAV5 to deliver therapeutic genes into equine corneal fibroblasts (ECFs) using enhanced green fluorescent protein (EGFP) marker gene and (ii) establish the safety of AAV5 vector for equine corneal gene therapy.

Animal Material—Primary ECF cultures were harvested from healthy donor equine corneas. Cultures were maintained at 370C in humidified atmosphere with 5% CO2.

Procedure—AAV5 vector expressing EGFP under control of hybrid cytomegalovirus (CMV) + chicken …

Chemosensitization Of Cancer Cells By Sirna Using Targeted Nanogel Delivery, Erin B. Dickerson, William H. Blackburn, Michael H. Smith, Laura B. Kapa, L. Andrew Lyon, John F. Mcdonald

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Background: Chemoresistance is a major obstacle in cancer treatment. Targeted therapies that enhance cancer cell sensitivity to chemotherapeutic agents have the potential to increase drug efficacy while reducing toxic effects on untargeted cells. Targeted cancer therapy by RNA interference (RNAi) is a relatively new approach that can be used to reversibly silence genes in vivo by selectively targeting genes such as the epidermal growth factor receptor (EGFR), which has been shown to increase the sensitivity of cancer cells to taxane chemotherapy. However, delivery represents the main hurdle for the broad development of RNAi therapeutics.

Methods: We report here …

Mir-107 Is Reduced In Alzheimer's Disease Brain Neocortex: Validation Study, Peter T. Nelson, Wang-Xia Wang

Pathology and Laboratory Medicine Faculty Publications

MiR-107 is a microRNA (miRNA) that we reported previously to have decreased expression in the temporal cortical gray matter early in the progression of Alzheimer's disease (AD). Here we study a new group of well-characterized human temporal cortex samples (N=19). MiR-107 expression was assessed, normalized to miR-124 and let-7a. Correlation was observed between decreased miR-107 expression and increased neuritic plaque counts (P< 0.05) and neurofibrillary tangle counts (P< 0.02) in adjacent brain tissue. Adjusted miR-107 and BACE1 mRNA levels tended to correlate negatively (trend with regression P< 0.07). In sum, miR-107 expression tends to be lower relative to other miRNAs as AD progresses.

Leiomyosarcoma Arising In The Pancreatic Duct: A Case Report And Review Of The Current Literature, Nicole D. Riddle, Brian C. Quigley, Irwin Browarsky, Marilyn M. Bui

Pathology and Cell Biology Faculty Publications

Context. Leiomyosarcomas are rare malignant smooth muscle tumors that may arise in any organ or tissue that contains smooth muscle, commonly within the gastrointestinal tract. They are most often found in the stomach, large and small intestines, and retroperitoneum. Primary pancreatic leiomyosarcoma is extremely rare, and to the best of our knowledge only 30 cases have been reported in the world literature since 1951. Our case represents the first to have a clear origin from the main pancreatic duct. Case Report. This case was diagnosed in a large, tertiary care center in Tampa, Florida. Pertinent information was obtained …

Rumen Microbial Population Dynamics During Adaptation To A High-Grain Diet, Samodha C. Fernando, H. T. Purvis Ii, F. Z. Najar, L. O. Sukharnikov, C. R. Krehbiel, T. G. Nagaraja, B. A. Roe, Udaya Desilva

Samodha C. Fernando Publications

High-grain adaptation programs are widely used with feedlot cattle to balance enhanced growth performance against the risk of acidosis. This adaptation to a high-grain diet from a high-forage diet is known to change the rumen microbial population structure and help establish a stable microbial population within the rumen. Therefore, to evaluate bacterial population dynamics during adaptation to a high-grain diet, 4 ruminally cannulated beef steers were adapted to a high-grain diet using a step-up diet regimen containing grain and hay at ratios of 20:80, 40:60, 60:40, and 80:20. The rumen bacterial populations were evaluated at each stage of the step-up …

5¢-O-B,G-Methylenetriphosphate Derivatives Of Nucleoside, Yousef Ahmadibeni, Chandravanu Dash, S. F. J. Le Grice, Keykavous Parang

Pharmacy Faculty Articles and Research

The solid-phase synthesis of 5¢-O-b,g-methylenetriphosphates of nucleosides 1–5 is described, where a 4-acetoxy-3-arylbenzyloxy group was used as a linker.

Efficacy And Safety Of Mitomycin C As An Agent To Treat Corneal Scarring In Horses Using An In Vitro Model, Dylan G. Buss, Ajay Sharma, Elizabeth A. Giuliano, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Objective—Mitomycin C (MMC) is used clinically to treat corneal scarring in human patients. We investigated the safety and efficacy of MMC to treat corneal scarring in horses by examining its effects at the early and late stages of disease using an in-vitro model.

Procedure—An in-vitro model of equine corneal fibroblast (ECF) developed was used. The equine corneal fibroblast or myofibroblast cultures were produced by growing primary ECF in the presence or absence of transforming growth factor beta-1 (TGFβ1) under serum-free conditions. The MMC dose for the equine cornea was defined with dose-dependent trypan blue exclusion and MTT [(3-4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays …

Isolation And Cultivation Of Equine Corneal Keratocytes, Fibroblasts And Myofibroblasts, Dylan G. Buss, Elizabeth A. Giuliano, Ajay Sharma, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Objective—To establish an in vitro model for the investigation of equine corneal wound healing. To accomplish this goal, a protocol to isolate and culture equine corneal keratocytes, fibroblasts and myofibroblasts was developed.

Animal material—Equine corneal buttons were aseptically harvested from healthy research horses undergoing humane euthanasia for reasons unrelated to this study. Slit-lamp biomicroscopy was performed prior to euthanasia by a board-certified veterinary ophthalmologist to ensure that all samples were harvested from horses free of anterior segment disease.

Procedure—Equine corneal stroma was isolated using mechanical techniques and stromal subsections were then cultured. Customized media at different culture conditions was used …

"Transduction Efficiency Of Aav 2/6, 2/8 And 2/9 Vectors For Delivering Genes In Human Corneal Fibroblasts ", Ajay Sharma, Arkasubhra Ghosh, Eric T. Hansen, Jason M. Newman, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

In the present study, cellular tropism and relative transduction efficiency of AAV2/6, AAV2/8 and AAV2/9 vectors have been tested for the cornea using primary cultures of human corneal fibroblasts. The AAV6, AAV8 and AAV9 serotypes having AAV2 ITR plasmid encoding for alkaline phosphatase (AP) gene were generated by transfecting HEK293 cell line with pHelper, pARAP4 and pRep/Cap plasmids. Primary cultures of human corneal fibroblasts were exposed to AAV infectious particles at two different doses (1×105 and 2×105 MOI). Cytochemistry and enzyme assays were used to measure delivered transgene expression in samples collected at 4 and 30 hours after AAV infection …

Cardiopulmonary Resuscitation Prescription Program: A Prospective Randomized Pilot Study, Marna R. Greenberg Do, Mph, Facep, Gavin Barr Md, Valerie Rupp Rn, Bsn, Nainesh C. Patel Md, Kevin R. Weaver Do, Kimberly Hamilton Ba, James F. Reed Iii Phd

Department of Emergency Medicine

No abstract provided.

Variable Number Of Tandem Repeat Polymorphisms (Vntrs) In The Acan Gene Associated With Pectus Excavatum, Michael W. Stacey, Serina Neumann, Ashley Dooley, Kara Segna, Robert Kelly, Donald Nuss, Anne Kuhn, Michael Goretsky, Annie Fecteau, Aimee Pastor, Virginia Proud

Bioelectrics Publications

No abstract provided.

Epigenetics: Blurring The Line Between Nature And Nurture, Elizabeth H. Rose

CMC Senior Theses

This long-standing nature versus nurture debate is cited in behavioral and physical expressions of disease dysfunctions, resiliencies, and recovery. Their purposes are noted both in scientific pursuits as well as literature. This discourse has been particularly intense in the fields of psychology, psychiatry, and biology where there is a long history of scientists’ attempts to disprove or discredit others’ intellectual and professional measures. Interestingly, recent advances in the neurosciences and genetic technologies have brought these fields closer together with a new focus – the interactional relationship between nature and nurture – epigenetics.

Vector Delivery Technique Affects Gene Transfer In The Cornea In Vivo, Rajiv R. Mohan, Ajay Sharma, Tyler C. Cebulko, Ashish Tandon

Pharmacy Faculty Articles and Research

Purpose: This study tested whether controlled drying of the cornea increases vector absorption in mouse and rabbit corneas in vivo and human cornea ex vivo, and studied the effects of corneal drying on gene transfer, structure and inflammatory reaction in the mouse cornea in vivo.

Methods: Female C57 black mice and New Zealand White rabbits were used for in vivo studies. Donor human corneas were used for ex vivo experiments. A hair dryer was used for drying the corneas after removing corneal epithelium by gentle scraping. The corneas received no, once, twice, thrice, or five times warm air for …

Authentication Of Biometric Features Using Texture Coding For Id Cards, Jonathan Blackledge, Eugene Coyle

Conference papers

The use of image based information exchange has grown rapidly over the years in terms of both e-to-e image storage and transmission and in terms of maintaining paper documents in electronic form. Further, with the dramatic improvements in the quality of COTS (Commercial-Off-The-Shelf) printing and scanning devices, the ability to counterfeit electronic and printed documents has become a widespread problem. Consequently, there has been an increasing demand to develop digital watermarking techniques which can be applied to both electronic and printed images (and documents) that can be authenticated, prevent unauthorized copying of their content and, in the case of printed …

Identification Of A Novel Cytokine Inducible Stat5 Phosphoserine Site (Ps193) That Positively Regulates Its Transcriptional Activity And Is Found Constitutively Activated In Certain Hematopoietic Cancers, Abhisek Mitra

Open Access Theses & Dissertations

Hematological malignancies such as leukemia and lymphoma, can develop from aberrant changes in the cell signaling molecules to drive their uncontrolled cellular proliferation and differentiation. Activation, maturation, expansion and differentiation of T cells are critically regulated by the dynamics of various transcription factors activated by a variety of cytokines. Additionally, multiple effector molecules that mediate these T cells dependent signals include the JAK (Janus Kinase)-STAT (Signal transducer and activator of transcription) cascade. These signaling proteins are activated in response to a broad array of cytokines. Constitutively activated JAKs and STATs have been described in several T cell malignancies. A growing …

Early Detection Of Response To Hydroxyurea Therapy In Patients With Sickle Cell Anemia., Samir K. Ballas, William F. Mccarthy, Nan Guo, Carlo Brugnara, Gail Kling, Robert L. Bauserman, Myron A. Waclawiw

Department of Medicine Faculty Papers

Red blood cells (RBC) and reticulocyte parameters were determined on peripheral blood from a subset of patients enrolled in the multicenter study of hydroxyuea (HU) in sickle cell anemia. Multiple blood samples were obtained every 2 weeks. Cellular indices were measured by flow cytometry. Generalized linear models were used to determine the relationship between the longitudinal trajectories of RBC and reticulocyte indices and HU usage. There was a significant relationship between HU usage and most of the RBC and reticulocyte indices. Hydroxyurea produced higher value trajectories than those generated by placebo usage for the hemoglobin (Hb) content of both the …

In Remembrance Of Denis Alan Trevor New, Robert L. Brent Dr.

The Selected Works of Robert Brent

None

Ionizing Radiation, Robert L. Brent Dr.

The Selected Works of Robert Brent

None

Expression Of The Intestinal Biomarkers Guanylyl Cyclase C And Cdx2 In Poorly Differentiated Colorectal Carcinomas., Brody Winn, Rosemarie Tavares, Andres Matoso, Lelia Noble, Jacqueline Fanion, Scott A Waldman, Murray B Resnick

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Guanylyl cyclase C, a receptor for bacterial diarrheagenic enterotoxins, is expressed selectively by intestinal epithelium and is an endogenous downstream target of CDX2. The expression of Guanylyl cyclase C is preserved throughout the adenoma/carcinoma sequence in the colorectum. Detection of Guanylyl cyclase C expression by reverse transcriptase-polymerase chain reaction is currently being validated as a technique to identify occult lymph node metastases in patients with colorectal cancer and for circulating cells in the blood for postoperative surveillance. Although Guanylyl cyclase C is widely expressed by well-differentiated colorectal cancer, its expression in poorly differentiated colorectal cancer has not been evaluated. A …

Safety Assessment For Tipranavir : A Protease Inhibitor Treatment For Hiv Infected Adults, Jaromir Mikl

Legacy Theses & Dissertations (2009 - 2024)

Dose-limiting adverse events associated with anti-retroviral therapy (ART) generally include gastro-intestinal (GI) issues such as vomiting and nausea. However, serious adverse events (SAEs) do occur, the most frequent of which include liver toxicities and renal impairment as well as recent evidence of cardio-vascular disease (CVD) risk.