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Articles 271 - 288 of 288
Full-Text Articles in Medicine and Health Sciences
A Twin Study Of Antisocial Behavior And Depression: Methodology, Etiology, And Comorbidity, Kelly A. Tracy
A Twin Study Of Antisocial Behavior And Depression: Methodology, Etiology, And Comorbidity, Kelly A. Tracy
Theses and Dissertations
The etiological connection between internalizing and externalizing disorders is poorly understood. This manuscript aims to investigate the roles of genes and then environment in the development of Major Depressive Disorder (MDD) and Antisocial Personality Disorder (ASPD) and the nature of their comorbidity in young adults. Data from a sample of 2,291 young adult male and female twins from the Young Adult Follow Up Study (YAFU) of the Virginia Twin Study of Adolescent Behavioral Development (VTSABD) were used to estimate the proportion of variation in these traits that can be accounted for by additive genetic, shared environmental, and unique environmental factors. …
Influence Of The Vitamin D3 Analog Eb 1089 On Senescence And Cell Death Pathways In The Response Of Breast Tumor Cells To Ionizing Radiation, Gerald Alan Demasters
Influence Of The Vitamin D3 Analog Eb 1089 On Senescence And Cell Death Pathways In The Response Of Breast Tumor Cells To Ionizing Radiation, Gerald Alan Demasters
Theses and Dissertations
A senescence-like growth arrest succeeded by rapid recovery of proliferative capacity is observed in MCF-7 breast tumor cells exposed to fractionated radiation (5 x 2Gy) alone. Exposure to the vitamin D3 analog EB 1089 (100nM) prior to irradiation converts the initial growth arrest response to cell death in part through the inhibition of radiation-induced senescence and promotion of both apoptotic and autophagic cell death. More importantly, EB 1089 was shown to profoundly reduce the rate of recovery following fractionated irradiation. The effect of EB 1089 on the temporal response to radiation is also observed in MCF-7 cells expressing caspase 3, …
Single Nucleotide Polymorphisms In The Folypoly-Gamma-Glutamate Synthetase Gene, Nadine Thompson
Single Nucleotide Polymorphisms In The Folypoly-Gamma-Glutamate Synthetase Gene, Nadine Thompson
Theses and Dissertations
Folic acid is an essential vitamin utilized in the one-carbon metabolism pathway for the synthesis of purine and thymidine nucleotides, which are necessary for cell growth and proliferation. As a result, the enzymes that participate in the metabolism of folic acid have been good targets for cancer chemotherapy. Folylpoly-γ-glutamate synthetase (FPGS) is an enzyme in the folate metabolism pathway that catalyzes the addition of glutamic acid to the naturally occurring folates, thereby allowing the retention of folate cofactors in cells. Similarly, in the case of cancer chemotherapy, antifolates, such as Lometrexol and Tomudex are retained in cells through the activity …
Action Of Tyrosyl Dna Phosphodiesterase On 3'-Phosphoglycolate Terminated Dna Strand Breaks, Haritha Tatavarthi
Action Of Tyrosyl Dna Phosphodiesterase On 3'-Phosphoglycolate Terminated Dna Strand Breaks, Haritha Tatavarthi
Theses and Dissertations
Free radical-mediated DNA double strand breaks (DSBs) are induced either directly by ionizing radiation or by certain chemicals like bleomycin. These breaks are terminated by 3'-PG (PO4CH2COOˉ) or 3'-phosphate groups formed as a result of fragmentation of deoxyribose. To study the nature of repair of these 3'-blocked breaks, we constructed substrates mimicking free-radical induced DSBs. Human and yeast tyrosyl DNA-phosphodiesterase (Tdpl) efficiently processed substrates with 3'-PGs, in either the presence or absence of magnesium, to give a 3'-phosphate. Gel filtration chromatography and western blotting codmed that the putative enzyme in human extracts that efficiently processed PG was indeed tyrosyl DNA-phosphodiesterase. …
Dual Regulation Of Telomerase Activity By Hsf1 And Its Role In Prostate Cancer Progression, Keith Douglas Ostergaard Jensen
Dual Regulation Of Telomerase Activity By Hsf1 And Its Role In Prostate Cancer Progression, Keith Douglas Ostergaard Jensen
Theses and Dissertations
It has been shown that the key components of the hsp90 chaperone complex, including hsp90, p23, hsp70, hsp40, and HOP (p60), associate with telomerase; however, their specific roles in telomerase function and tumor progression have not yet been defined. HSF1, the primary mammalian heat shock protein transcription factor, may affect telomerase activity and transformation by regulating the expression of several hsp90 chaperone complex proteins in response to stress as well as regulating the transcription of hTERT, the protein subunit of telomerase.In our in vitro model of prostate cancer progression, as cells progress from immortal but non-tumorigenic (P69) to tumorigenic (M2182) …
Immunotoxicological Evaluation Of Critical Windows Of Development Following Exposure To 1,2:5,6 Dibenzanthracene In B6c3f1 Mice, Denise Marie Hernandez
Immunotoxicological Evaluation Of Critical Windows Of Development Following Exposure To 1,2:5,6 Dibenzanthracene In B6c3f1 Mice, Denise Marie Hernandez
Theses and Dissertations
Numerous findings have suggested that the increased prevalence of childhood illnesses such as cancer, infection, and allergy may be due to environmental exposures. One such cause may be maternal smoking or passive smoke exposure. Known immunotoxicants in cigarette smoke and environmental pollution include polycyclic aromatic hydrocarbons such as 1,2:5,6 Dibenzanthracene (DBA). The objective of these studies was to evaluate the immunosuppressive effects of DBA on various stages of immune system development. Adult mice were administered DBA daily in corn oil at dose levels of 158, 500, 1580, and 5000 µglkg S.C. for 28 days. Immunosuppression was not observed at levels …
Glutamate Excitotoxicty Activates A Novel Calcium Permeable Ion Channel In Cultured Hippocampal Neurons, Laxmikant Sudhir Deshpande
Glutamate Excitotoxicty Activates A Novel Calcium Permeable Ion Channel In Cultured Hippocampal Neurons, Laxmikant Sudhir Deshpande
Theses and Dissertations
Glutamate excitotoxicity is the predominant mechanism implicated in neuronal cell death associated with neurological disorders such as stroke, epilepsy, traumatic brain injury and ALS. Excessive stimulation of NMDA subtypes of glutamate receptors leads to protracted intracellular calcium elevations triggering calcium mediated neurotoxic mechanisms culminating in delayed neuronal cell death. In addition, glutamate excitotoxicity induces a NMDA dependent extended neuronal depolarization mediated by continuous calcium influx that correlates with delayed neuronal death. Attempts to prevent neuronal death by blocking calcium entry into the neurons using calcium channel blockers or NMDA receptor antagonists have failed to provide any beneficial effects in clinical …
Relationship Between Cb1 And S1p Receptors In The Central Nervous System, Lauren Michele Collier
Relationship Between Cb1 And S1p Receptors In The Central Nervous System, Lauren Michele Collier
Theses and Dissertations
There is significant sequence homology and anatomical co-distribution between cannabinoid (CB1) and sphingosine-1-phosphate (S1P) receptors in the CNS, but potential functional relationships between these lysolipid receptors have not been examined. Therefore, to investigate possible relationships between these two systems at the level of G-protein activation, agonist-stimulated [35S]GTPγS binding and autoradiography were conducted. Autoradiographic studies were first performed to localize receptor-mediated G-protein activation in mouse brain. Coronal brain slices were processed for stimulation of [35S]GTPγS binding using the synthetic cannabinoid agonist WIN 55,212-2 (WIN) or SIP. High levels of WIN- and S1P-stimulated [35S]GTPγS binding were observed in the caudate putamen, hippocampus, …
Pathological Upregulation Of A Calcium-Stimulated Phosphatase, Calcineurin, In Two Models Of Neuronal Injury, Jonathan Elledge Kurz
Pathological Upregulation Of A Calcium-Stimulated Phosphatase, Calcineurin, In Two Models Of Neuronal Injury, Jonathan Elledge Kurz
Theses and Dissertations
Excitotoxic calcium influx and activation of calcium-regulated systems is a common event in several types of neuronal injury. This mechanism has been the focus of intense research, with the hope that a more complete understanding of how neuronal injury affects calcium-regulated systems will provide effective treatment options. This study examines one such calcium-stimulated enzyme, calcineurin, in the context of two common neurological pathologies, status epilepticus and traumatic brain injury.Status epilepticus was induced by pilocarpine injection. NMDA-dependent increases in calcineurin activity were observed in cortical and hippocampal homogenates. Upon closer examination, the most profound increases in activity were found to be …
The Role Of Gonadal Hormones On Opioid Receptor Protein Density In Arthritic Rats, Matthew Kren
The Role Of Gonadal Hormones On Opioid Receptor Protein Density In Arthritic Rats, Matthew Kren
Theses and Dissertations
The majority of research on the endogenous opioid system has focused on various pain assays and the efficacy of different opioid agonists. However, minimal attention has been focused on the effects of gonadal hormones and their impact on the opioid peptide system. The present study was designed to determine the effects of modulation of gonadal hormones on the opioid receptor protein levels in Complete Freund's Adjuvant (CFA)-treated arthritic and non-arthritic male and female Lewis rats. Midbrain and spinal cord tissues were collected for comparison of the μ, δ, and κ receptor protein levels in arthritic and non-arthritic animals. Male gonadectomy …
Characterization Of The Tcof1 Gene Using A Neuroblastoma Cell Line And A Mouse Model, Lin Li
Characterization Of The Tcof1 Gene Using A Neuroblastoma Cell Line And A Mouse Model, Lin Li
Theses and Dissertations
Treacher Collins syndrome (TCS) is an autosomal dominant craniofacial development disorder and is caused by mutations in the TCOF1 gene. The TCOFl protein treacle is a nucleolar protein and may function in ribosome biogenesis.Previously, we identified downstream candidate genes using microarray analysis after manipulating Tcofl levels in a murine neuroblastoma (NB) cell line. The list of genes includes cell cycle genes as well as the transcription factors Cnbp and Tbx2, which are known to affect the cell cycle through the c-myc and p19-Mdm2-p53-p21 pathways respectively. To further characterize the cellular effects of Tcofl, stably transfected NB cell lines with overexpression …
The Study Of The Effect Of Drugs Of Abuse On Protein Kinase A Activity In Mouse Brain And Spinal Cord, George D. Dalton
The Study Of The Effect Of Drugs Of Abuse On Protein Kinase A Activity In Mouse Brain And Spinal Cord, George D. Dalton
Theses and Dissertations
Morphine and Δ9-THC are drugs that produce analgesia and rewarding effects. However, chronic treatment with morphine and Δ9-THC produces problematic side-effects including tolerance and physical dependence. The cellular mechanisms underlying opioid and cannabinoid antinociceptive tolerance have been studied for years. Research has demonstrated that the expression of morphine and Δ9-THC antinociceptive tolerance may be mediated through intracellular signaling pathways, such as the adenylyl cyclase /Protein Kinase A (PKA) cascade. The present study investigated the role of PKA in the expression of morphine and Δ9-THC antinociceptive tolerance. Male Swiss Webster mice were treated chronically with morphine or Δ9-THC and the warm-water …
Post-Juvenile Brain Development Modulates Seizure Characteristics And Diazepam Efficacy In The Rat Pilocarpine-Se Model, William H. Holbert Ii
Post-Juvenile Brain Development Modulates Seizure Characteristics And Diazepam Efficacy In The Rat Pilocarpine-Se Model, William H. Holbert Ii
Theses and Dissertations
These studies were completed to examine how status epilpeticus seizure characteristics are modulated during post-juvenile brain development. This may determine if postnatal age in rats is a better identifier of stages of post-juvenile brain development. The first study fully detailed the acute discrete seizure phase of the rat pilocarpine-SE model. Results for this study showed that Racine behavioral severity score, spike frequency, and seizure severity during the acute discrete seizure phase change in relation to post-juvenile brain developmental stages. The second study fully detailed early and late patterns of status epilepticus. Results for this study displayed modulation of time in …
The Effects Of Footshock On The Reinforcing Efficacy Of Cocaine In Male Long-Evans Rats, Elizabeth S. Hendrick
The Effects Of Footshock On The Reinforcing Efficacy Of Cocaine In Male Long-Evans Rats, Elizabeth S. Hendrick
Theses and Dissertations
Many links exist between cocaine abuse and stress. The literature and laboratory studies in rats suggest that this could be because stress increases the reinforcing efficacy of cocaine. Using male Long-Evans rats, experiments in this thesis tested effects of footshock on the reinforcing efficacy of cocaine using a progressive ratio schedule of reinforcement. They also examined effects of footshock on the reinforcing efficacy of a half-maximal dose of cocaine. Finally, they tested the effects of footshock on cocaine self-administration in rats initially resistant to acquisition of cocaine self-administration. Footshock did not increase reinforcing efficacy of cocaine on a PR schedule …
Genetic Dissection Of Behavioral And Neurogenomic Responses To Acute Ethanol, Aaron Wolen
Genetic Dissection Of Behavioral And Neurogenomic Responses To Acute Ethanol, Aaron Wolen
Theses and Dissertations
Individual differences in initial sensitivity to ethanol are strongly related to the heritable risk of alcoholism in humans. To elucidate key molecular networks that modulate ethanol sensitivity we performed a systems genetics analysis of ethanol-responsive gene expression in brain regions of the mesocorticolimbic reward circuit (prefrontal cortex, nucleus accumbens and ventral midbrain) across the BXD RI panel, a highly diverse family of isogenic mouse strains before and after treatment with ethanol. Acute ethanol altered the expression of ~2,750 genes in one or more regions and 400 transcripts were jointly modulated in all three. Ethanol-responsive gene networks were extracted with a …
Titrating And Evaluating Multiple Drug Regimens Within Subjects, Margaret Shih
Titrating And Evaluating Multiple Drug Regimens Within Subjects, Margaret Shih
Theses and Dissertations
The dosing of combination therapies is commonly undertaken empirically by practicing physicians, and there is a lack of a coherent algorithm to approach the problem of combination dosing. Current methods of evaluating multiple drug combinations in clinical trials generally do not provide information regarding the location of more effective dosages when the combination is not found to differ from the standard, even though the absence of a difference does not necessarily mean the new combination is ineffective. Additionally, if a new combination is found to be more effective, often a large proportion of the subjects has not benefited from the …
Nosocomial Respiratory Tract Infections Associated With The Use Of Ventilatory Support Systems: Epidemiological And Bacteriological Study Of The Effect Of Changing Breathing Circuits At 24 Or 48 Hours, Virginia Archer Lamb
Theses and Dissertations
Nosocomial (hospital-acquired) pneumonia (HAP) continues to be an important cause of morbidity and mortality in the hospital. HAP is the third most common nosocomial infection after urinary tract and surgical wound infections. In addition, HAP is the nosocomial infection with the highest mortality rate. These infections are often difficult to treat, because most are caused by Gram-negative bacilli (GNB) that may be highly resistant to antimicrobial agents. HAPs frequently occur in intensive care patients with underlying lung and/or systemic diseases. Many patients are intubated and are on assisted ventilation. Several sources of infection associated with ventilators or respirators have been …
Comparison Of Virulent And Avirulent Legionella Pneumophila And Evaluation Of Fish As A Potential Environmental Reservoir/Experimental Model, Sandra Reading Sommer
Comparison Of Virulent And Avirulent Legionella Pneumophila And Evaluation Of Fish As A Potential Environmental Reservoir/Experimental Model, Sandra Reading Sommer
Theses and Dissertations
Legionella pneumophila was first recognized as a cause of human pneumonia in 1976 . Since then, much has been learned about the microbiology, pathophysiology and epidemiology of this organism. The features which permit one strain but not another to invade human lung tissue and produce disease remain incompletely understood. This study e valuated several attributes of a virulent and an avirulent strain of L. pneumophila in an attempt to identify characteristics which would distinguish the two. Evaluation of a new medium, buffered egg yolk agar, showed that virulence was maintained after 26 passages, which was the same as the buffered …