Medical Sciences Commons^™

Pseudomonas Aeruginosa-Candida Albicans Interactions: Localization And Fungal Toxicity Of A Phenazine Derivative, Jane Gibson, Arpanah Sood, Deborah A. Hogan

Dartmouth Scholarship

Phenazines are redox-active small molecules that play significant roles in the interactions between pseudomonads and diverse eukaryotes, including fungi. When Pseudomonas aeruginosa and Candida albicans were cocultured on solid medium, a red pigmentation developed that was dependent on P. aeruginosa phenazine biosynthetic genes. Through a genetic screen in combination with biochemical experiments, it was found that a P. aeruginosa-produced precursor to pyocyanin, proposed to be 5-methyl-phenazinium-1-carboxylate (5MPCA), was necessary for the formation of the red pigmentation. The 5MPCA-derived pigment was found to accumulate exclusively within fungal cells, where it retained the ability to be reversibly oxidized and reduced, and its …

Factors Associated With Hydrocarbon Ingestion In Children, Emaduddin Siddiqui, Junaid Razzak, Farah Naz, Sabeena Jalal Khan

Department of Emergency Medicine

OBJECTIVE: To investigate the types of hydrocarbon ingested by children and identify factors associated with hydrocarbons ingestion.

PATIENTS AND METHODS: It was a hospital based case control study in which medical records of sixty seven children with hydrocarbon ingestion, admitted through emergency department between January 2001 to December 2005 of Aga Khan Hospital were reviewed. Variables such as age, sex, types of hydrocarbons, amount ingested, socioeconomic status, family size, number of children, type of containers, trend of ingestion during hot weather, length of stay at hospital along with the outcomes were evaluated.

RESULTS: Out of 67 patients, 53 (79%) were …

The Aryl Hydrocarbon Receptor Binds To E2f1 And Inhibits E2f1-Induced Apoptosis., Jennifer L Marlowe, Yunxia Fan, Xiaoqing Chang, Li Peng, Erik S Knudsen, Ying Xia, Alvaro Puga

Kimmel Cancer Center Faculty Papers

Cellular stress by DNA damage induces checkpoint kinase-2 (CHK2)-mediated phosphorylation and stabilization of the E2F1 transcription factor, leading to induction of apoptosis by activation of a subset of proapoptotic E2F1 target genes, including Apaf1 and p73. This report characterizes an interaction between the aryl hydrocarbon (Ah) receptor (AHR), a ligand-activated transcription factor, and E2F1 that results in the attenuation of E2F1-mediated apoptosis. In Ahr(-/-) fibroblasts stably transfected with a doxycycline-regulated AHR expression vector, inhibition of AHR expression causes a significant elevation of oxidative stress, gammaH2A.X histone phosphorylation, and E2F1-dependent apoptosis, which can be blocked by small interfering RNA-mediated knockdown of …

Maternal Cocaine Administration In Mice Alters Dna Methylation And Gene Expression In Hippocampal Neurons Of Neonatal And Prepubertal Offspring, Svetlana I. Novikova, Fang He, Jie Bai, Nicholas J. Cutrufello, Michael S. Lidow, Ashiwel S. Undieh

College of Pharmacy Faculty Papers

Previous studies documented significant behavioral changes in the offspring of cocaine-exposed mothers. We now explore the hypothesis that maternal cocaine exposure could alter the fetal epigenetic machinery sufficiently to cause lasting neurochemical and functional changes in the offspring. Pregnant CD1 mice were administered either saline or 20 mg/kg cocaine twice daily on gestational days 8-19. Male pups from each of ten litters of the cocaine and control groups were analyzed at 3 (P3) or 30 (P30) days postnatum. Global DNA methylation, methylated DNA immunoprecipitation followed by CGI(2) microarray profiling and bisulfite sequencing, as well as quantitative real-time RT-PCR gene expression …

Screening Assay For Enzymes Involved In Pathophysiology Using Seldi-Tof Mass Spectrometr, Khalid M. Elased, Mariana Morris

Pharmacology and Toxicology Faculty Publications

The invention provides methods for quantifying enzymatic activity of an enzyme with a known substrate. The methods employ SELDI-TOF mass spectrometry, and are suitable, in particular, for assaying aspects of the renin-angiotensin system. The methods may be utilized to assess and/or monitor biological conditions associated with the renin-angiotensin system prior to the manifestation of known physiological and biomarkers for such conditions. The methods are suitable for analysis of pharmacological effectors of the renin-angiotensin system, and are particularly suitable for automation and high-throughput screening assay design.

Diverse Antidepressants Increase Cdp-Diacylglycerol Production And Phosphatidylinositide Resynthesis In Depression-Relevant Regions Of The Rat Brain, Kimberly R. Tyeryar, Habiba O.U. Vongtau, Ashiwel S. Undieh

College of Pharmacy Faculty Papers

BACKGROUND: Major depression is a serious mood disorder affecting millions of adults and children worldwide. While the etiopathology of depression remains obscure, antidepressant medications increase synaptic levels of monoamine neurotransmitters in brain regions associated with the disease. Monoamine transmitters activate multiple signaling cascades some of which have been investigated as potential mediators of depression or antidepressant drug action. However, the diacylglycerol arm of phosphoinositide signaling cascades has not been systematically investigated, even though downstream targets of this cascade have been implicated in depression. With the ultimate goal of uncovering the primary postsynaptic actions that may initiate cellular antidepressive signaling, we …

Translational Regulatory Mechanisms Of The Rat And Human Multidrug Resistance Protein 2, Yuanyuan Zhang

University of Kentucky Doctoral Dissertations

Multidrug resistance protein 2 (MRP2) is the second member the C subfamily in the superfamily of adenosine triphosphate (ATP)-binding cassette (ABC) efflux transporters. MRP2 is a critical player for generation of bile acidindependent bile flow and biliary excretion of glutathione, glucuronate and sulfate conjugates of endo- and xenobiotics. Dysfunctional expression of MRP2 is associated with Dubin-Johnson Syndrome.

Pathological and physiological states or xenobiotics change the MRP2 expression level. Under some conditions, expression of the human MRP2 and rat Mrp2 proteins are regulated at the translation level. There are several transcription initiation sites in MRP2/Mrp2 gene. The 5’ untranslated regions (5’UTRs) …

Zinc Deficiency And Mechanisms Of Endothelial Cell Dysfunction, Huiyun Shen

University of Kentucky Doctoral Dissertations

Atherosclerosis is a chronic inflammatory disease thought to be initiated by endothelial cell dysfunction. Research described in this dissertation is focused on the role of zinc deficiency in endothelial cell activation with an emphasis on the function of the transcription factors nuclear factor-κB (NF-κB), peroxisome proliferator activated receptor (PPAR), and the aryl hydrocarbon receptor (AhR), which all play critical roles in the early pathology of atherosclerosis. Cultured porcine aortic vascular endothelial cells were deprived of zinc by the zinc chelator TPEN and/or treated with the NF-κB inhibitor CAPE or the PPARγ agonist rosiglitazone, followed by measurements of PPARα expression, cellular …

Endothelial Cell Dysfunction By Environmental Contaminants, Elizabeth Grace Oesterling

University of Kentucky Doctoral Dissertations

Within the last few decades, epidemiological evidence has linked exposure to air pollution, both its particles and its organic components, with cardiovascular disease (CVD) progression. CVD is a life long disease with the disruption of the endothelium being the inaugural event in this inflammatory process. The vascular endothelium is extremely susceptible to environmental insults given its tremendous surface area and that it is in constant contact with blood and components circulating within the blood, including xenobiotics. The endothelium is important as a barrier from blood constituents however, dysfunction of this barrier leads to the influx of lymphocytes and granulocytes that …

Nitration And Inactivation Of Manganese Superoxide Dismutase Plays A Critical Role In Metabolic Switch, Muthuswamy Anantharaman

University of Kentucky Doctoral Dissertations

Alzheimer’s disease (AD) is a multifactorial, progressive, age-related neurodegenerative disease. Oxidative stress hypothesis is most prevalent and is gaining significant support. Inspite of the progress achieved on oxidative stress related damages in AD brain; the modification occurring on the various cellular antioxidant enzymes antioxidant has not been identified. Tyrosine nitration, a marker for peroxynitrite induced oxidative damage to protein is widespread in AD brain and Manganese superoxide dismutase (MnSOD), primary mitochondrial antioxidant enzyme is prone to peroxynitrite induced nitration and inactivation. Nitration of proteins involved in energy metabolism has been demonstrated in AD brain, which may explain the altered glucose …

Guest Perspective - Dr. Robert L. Brent, Robert L. Brent

The Selected Works of Robert Brent

No abstract provided.

Book Review: Drugs During Pregnancy And Lactation: Treatment Options And Risk Assessment, Robert L. Brent

The Selected Works of Robert Brent

No abstract provided.

Implications For The Hsf2/Prc1 Interaction And Regulation Of Condensin By Phosphorylation During Mitosis, Lynea Alene Murphy

University of Kentucky Doctoral Dissertations

At the beginning of mitosis, chromosomes are condensed and segregated to facilitate correct alignment later in cytokinesis. Condensin is the pentameric enzyme responsible for this DNA compaction and is composed of two structural maintenance of chromosomes (SMC) subunits and three non-SMC subunits. Condensin mutations generate chromosomal abnormalities due to improper segregation, leading to genome instability and eventual malignant transformation of the cell. Cdc2 phosphorylation of the non-SMC subunits, CAP-G, CAP-D2, and CAP-H, has been demonstrated to be important for condensin supercoiling activity and function. While these subunits are thought to be phosphorylated by Cdc2, the exact sites have not yet …

Reciprocal Regulation Of Par-4 And Caspase-8 In The Trail Signaling Pathway, Padhma Ranganathan

University of Kentucky Doctoral Dissertations

Par‐4 is a pro‐apoptotic tumor suppressor that is mutated, suppressed or inactivated in cancer. Par‐4 exploits components of the extrinsic pathway to cause apoptosis selectively of cancer cells. This study identified Par‐4 as an essential component of the apoptotic pathway induced by TRAIL, which selectively targets cancer cells. RNA interference‐mediated knockdown of Par‐4 rendered cancer cells unresponsive to TRAIL‐induced apoptosis. Cells with knocked‐down levels of Par‐4 were deficient in the activation of the apoptosis‐initiator caspase‐8 and the apoptosis‐effector caspase‐3 in response to TRAIL. Par‐4 was identified as a critical mediator of membrane translocation of caspase‐8 and the adapter protein FADD. …

Environmental Causes Of Human Congenital Malformations: The Physician's Role In Dealing With These Complex Clinical Problems Caused By Environmental And Genetic Factors., Robert L. Brent

The Selected Works of Robert Brent

No abstract provided.

Bio-Monitoring The Elimination Of Folic Acid-Preventable Spina Bifida And Anencephaly, Robert L. Brent

The Selected Works of Robert Brent

No abstract provided.