Medicine and Health Sciences Commons^™

The Role Of Extracellular Matrix And Matrix-Degrading Proteases In Neonatal Hypoxic-Ischemic Injury, Christopher C. Leonardo

USF Tampa Graduate Theses and Dissertations

Improvements in medical care over recent decades have increased the number of premature and low birth weight infants that survive hypoxic-ischemic (H-I) insults. Because there is a rising incidence in diseases associated with these events, it is critical to develop effective therapies to treat the various resulting neuropathies. Extracellular matrix constitutes the majority of brain parenchyma. Lecticans and matrix-degrading proteases including ADAMTSs (a disintegrin and metalloproteinase with thrombospondin repeats) and matrix metalloproteinases (MMPs) exert effects on cell viability and may be associated with either protective or destructive processes after H-I. Both ADAMTSs (Cross et al. 2006; Tian et al. 2007) …

Effects Of Acute Ethyl Alcohol Consumption On A Psychophysical Measure Of Lateral Inhibition In Human Vision., Kevin D Johnston, Brian Timney

Brain and Mind Institute Researchers' Publications

Acute consumption of ethyl alcohol affects a variety of visual functions. However, there have been few systematic attempts to investigate the neural mechanisms underlying these effects. Here, we employed the Westheimer paradigm to investigate the hypothesis that alcohol reduces lateral inhibition within human "perceptive fields", the psychophysical analogue of physiological receptive fields. Westheimer functions obtained under alcohol and no-alcohol conditions at photopic, mesopic, and scotopic levels of adaptation showed changes consistent with an alcohol-induced decrease in lateral inhibition. We conclude that this decrease in lateral inhibition may be responsible for some of the changes in visual perception that result from …

Drug Overdose: A Wake Up Call! Experience At A Tertiary Care Centre In Karachi, Pakistan, Muhammad Junaid Patel, Muhammad Shahid, Mehmood Riaz, Waqaruddin Kashif, Syed Imran Ayaz, Muhammad Shoaib Khan, A. Jawwad Samdani, Ayesha L Sorathia, Muhammad Furqan

Department of Emergency Medicine

OBJECTIVE: To study the characteristics of patients admitted with drug overdose caused either by accidental overdose of the prescribed medications or as an act of deliberate self harm (DSH) at a tertiary care hospital in Karachi, Pakistan.METHODS: A retrospective case series review was conducted at the Aga Khan University Hospital from January 2002 to October 2006. Three hundred and twenty four adult patients admitted with drug overdose were included in the study.RESULTS: Our sample group revealed mean age of 36.2 +/- 17.0 years, more females (59%), housewives (34%), and students (20%). Fifty six percent of patients committing DSH were married …

Response Of Endothelial Cells To Stressors: The Impact Of Aging And Diabetes, Katie Mclellan

Loma Linda University Electronic Theses, Dissertations & Projects

Preliminary research indicates there is some impairment of the endothelial cells to respond to single stressors such as local heat, shear stress, and global heat in older people and people who have diabetes. The response of the skin blood flow to local heat is an indicator of the endothelial cells ability to cope with stress. In addition, factors such as thicker subcutaneous fat and skin moisture may impair the skin’s ability to dissipate heat. For older people and people with diabetes, this endothelial dysfunction may cause an even more diminished response to multiple stressors. However, no studies have examined the …

Novel Binding Domains Mediate Binding Of Hpv 16 E6 To Fadd And Procaspase 8, Sandy S. Tungteakkhun

Loma Linda University Electronic Theses, Dissertations & Projects

To evade the host response to infection, viruses have developed means to survive and propagate. HPV 16, a causative agent of cervical cancer and of some cases of oropharyngeal cancers, is one example. We have reported that the early viral protein E6 binds to proteins necessary for propagation of the apoptotic signal following receptor/ligand interactions, such as those mediated by FADD DED and procaspase 8 DED. E6 expression leads to the dose-dependent accelerated degradation of FADD and the protection of E6-expressing cells from Fas-induced apoptosis. Surprisingly, the splice isoforms of E6, E6_large and E6*, affect the stability of procaspase …

Mechanisms Of T Helper Cell Modulation In A Simulated Space Radiation Environment, Asma Rizvi

Loma Linda University Electronic Theses, Dissertations & Projects

Exposure to solar particle events (SPEs) poses the most serious threat to astronaut health. Due to this radiation environment, exploration of the solar system beyond Earth’s orbit entails many risks for the crew on these deep space missions. Depression or dysfunction of the immune system is a major concern due to its high radio-sensitivity; potential consequences include overwhelming infection, development of cancer, fibrosis, and poor wound healing. Astronauts are also exposed to low dose/low dose rate (LDR) radiation. A three month stay at the international space station exposes them to ~ 0.05 Gy of radiation.

C57BL/6 mice received LDR gamma-radiation …

Primary Care Physicians And Insulin Initiation: Multiple Barriers, Lack Of Knowledge Or Both?, Serge Jabbour, Md, Facp, Face

Department of Medicine Faculty Papers

Primary care physicians (PCPs) provide diabetes care for 82% of patients with type 2 diabetes (1). Many patients with type 2 diabetes will eventually need insulin. The UKPDS (2) showed that ß-cell failure is progressive. From 50% of normal ß-cell function present at diagnosis, there is a steady decline with almost complete loss of ß-cell mass within 10-15 years, even earlier in some patients. On average, as many as 40-80% of patients with type 2 diabetes will need insulin within 10 years after diagnosis (1,2). These statistics can vary between patients and depending on the different agents used after the …

Supracutaneous Vibrotactile Perception Threshold At Various Non-Glabrous Body Loci, Miriam Bikah, M. Susan Hallbeck, John H. Flowers

Department of Psychology: Faculty Publications

Researchers at the University of Nebraska–Lincoln are currently designing a wearable/portable neutron detector. As an alerting mechanism, the device will transmit vibration to the wearer’s skin in the presence of hazardous levels of neutron radiation. The present study was designed to help in the ergonomically correct body placement of the neutron detection device while providing numerical values for vibratory thresholds at the surface of various non-glabrous body loci. The aim of the study was to investigate the underlying effects of locus stimulated, amount of subcutaneous fat around a specific body site and gender on low frequency vibration thresholds. Thirty-six participants, …

Demyelinating And Nondemyelinating Strains Of Mouse Hepatitis Virus Differ In Their Neural Cell Tropism., Jayasri Das Sarma, Kathryn Iacono, Lilli Gard, Ryan Marek, Lawrence C. Kenyon, Michael Koval, Susan R. Weiss

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Some strains of mouse hepatitis virus (MHV) can induce chronic inflammatory demyelination in mice that mimics certain pathological features of multiple sclerosis. We have examined neural cell tropism of demyelinating and nondemyelinating strains of MHV in order to determine whether central nervous system (CNS) cell tropism plays a role in demyelination. Previous studies demonstrated that recombinant MHV strains, isogenic other than for the spike gene, differ in the extent of neurovirulence and the ability to induce demyelination. Here we demonstrate that these strains also differ in their abilities to infect a particular cell type(s) in the brain. Furthermore, there is …

A New Model For Hemoglobin Ingestion And Transport By The Human Malaria Parasite Plasmodium Falciparum., Michelle D Lazarus, Timothy G Schneider, Theodore F Taraschi

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The current model for hemoglobin ingestion and transport by intraerythrocytic Plasmodium falciparum malaria parasites shares similarities with endocytosis. However, the model is largely hypothetical, and the mechanisms responsible for the ingestion and transport of host cell hemoglobin to the lysosome-like food vacuole (FV) of the parasite are poorly understood. Because actin dynamics play key roles in vesicle formation and transport in endocytosis, we used the actin-perturbing agents jasplakinolide and cytochalasin D to investigate the role of parasite actin in hemoglobin ingestion and transport to the FV. In addition, we tested the current hemoglobin trafficking model through extensive analysis of serial …

Connexin Expression And Gap Junctional Coupling In Human Cumulus Cells: Contribution To Embryo Quality, Hong-Xing Wang, Dan Tong, Faraj El-Gehani, Francis R. Tekpetey, Gerald M. Kidder

Physiology and Pharmacology Publications

Gap junctional coupling among cumulus cells is important for oogenesis since its deficiency in mice leads to impaired folliculogenesis. Multiple connexins (Cx), the subunits of gap junction channels, have been found within ovarian follicles in several species but little is known about the connexins in human follicles. The aim of this study was to determine which connexins contribute to gap junctions in human cumulus cells and to explore the possible relationship between connexin expression and pregnancy outcome from in vitro fertilization (IVF). Cumulus cells were obtained from IVF patients undergoing intracytoplasmic sperm injection (ICSI). Connexin expression was examined by RT-PCR …

Muc4 And Muc5ac Are Highly Specific Tumour-Associated Mucins In Biliary Tract Cancer., W. R. Matull, F. Andreola, A. Loh, Z. Adiguzel, M. Deheragoda, U. Qureshi, Surinder K. Batra, D. M. Swallow, S. P. Pereira

Journal Articles: Biochemistry & Molecular Biology

Alterations in epithelial mucin expression are associated with carcinogenesis, but there are few data in biliary tract cancer (BTC). In pancreatic malignancy, MUC4 is a diagnostic and prognostic tumour marker, whereas MUC5AC has been proposed as a sensitive serological marker for BTC. We assessed MUC4 and MUC5AC expression in (i) prospectively collected bile and serum specimens from 72 patients with biliary obstruction (39 BTC) by real-time reverse transcriptase-PCR (qPCR) and western blot analysis, and (ii) 79 archived biliary tissues (69 BTC) by immunohistochemistry. In bile, MUC4 protein was detected in 27% of BTC and 29% of primary sclerosing cholangitis (PSC) …

Prescription Of Medicines By Medical Students Of Karachi, Pakistan: A Cross-Sectional Study, Syed Nabeel Zafar, Reema Syed, Sana Waqar, Faria A. Irani, Sarah Saleem

Community Health Sciences

Background: Prescription of medicines by non-doctors is an issue with serious global implications. To our knowledge prescription of drugs by medical and non-medical students has not been studied before. We aimed to determine the practice and attitudes of drug prescription by medical students and: a) how non-medical students respond to this practice, b) How this compares with the attitudes and practices of non-medical students. Methods: A cross-sectional study was conducted on a sample of 600 students randomly selected from 2 medical and 2 non-medical universities. Ethical requirements were ensured and data was collected using self administered questionnaires. The Chi square …

The Synthetic Triterpenoid Cddo-Methyl Ester Modulates Microglial Activities, Inhibits Tnf Production, And Provides Dopaminergic Neuroprotection, Thi A. Tran, Melissa K. Mccoy, Michael B. Sporn, Malú G. Tansey

Dartmouth Scholarship

Recent animal and human studies implicate chronic activation of microglia in the progressive loss of CNS neurons. The inflammatory mechanisms that have neurotoxic effects and contribute to neurodegeneration need to be elucidated and specifically targeted without interfering with the neuroprotective effects of glial activities. Synthetic triterpenoid analogs of oleanolic acid, such as methyl-2-cyano-3,12-dioxooleana-1,9-dien-28-oate (CDDO-Me, RTA 402) have potent anti-proliferative and differentiating effects on tumor cells, and anti-inflammatory activities on activated macrophages. We hypothesized that CDDO-Me may be able to suppress neurotoxic microglial activities while enhancing those that promote neuronal survival. Therefore, the aims of our study were to identify specific …

Early Diagnosis Of Pancreatic Cancer: Neutrophil Gelatinase-Associated Lipocalin As A Marker Of Pancreatic Intraepithelial Neoplasia., N. Moniaux, S. Chakraborty, M. Yalniz, J. Gonzalez, Valerie K. Shostrom, J. Standop, Subodh M. Lele, Michel M. Ouellette, Parviz M. Pour, Aaron Sasson, R. E. Brand, Michael A. Hollingsworth, Maneesh Jain, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Pancreatic cancer is a highly lethal malignancy with a dismal 5-year survival of less than 5%. The scarcity of early biomarkers has considerably hindered our ability to launch preventive measures for this malignancy in a timely manner. Neutrophil gelatinase-associated lipocalin (NGAL), a 24-kDa glycoprotein, was reported to be upregulated nearly 27-fold in pancreatic cancer cells compared to normal ductal cells in a microarray analysis. Given the need for biomarkers in the early diagnosis of pancreatic cancer, we investigated the expression of NGAL in tissues with the objective of examining if NGAL immunostaining could be used to identify foci of pancreatic …

Cif Is Negatively Regulated By The Tetr Family Repressor Cifr, Daniel P. Maceachran, Bruce A. Stanton, George A. O'Toole

Dartmouth Scholarship

We previously reported that the novel Pseudomonas aeruginosa toxin Cif is capable of decreasing apical membrane expression of the cystic fibrosis transmembrane conductance regulator (CFTR). We further demonstrated that Cif is capable of degrading the synthetic epoxide hydrolase (EH) substrate S-NEPC [(2S,3S)-trans-3-phenyl-2-oxiranylmethyl 4-nitrophenol carbonate], suggesting that Cif may be reducing apical membrane expression of CFTR via its EH activity. Here we report that Cif is capable of degrading the xenobiotic epoxide epibromohydrin (EBH) to its vicinal diol 3-bromo-1,2-propanediol. We also demonstrate that this epoxide is a potent inducer of cif gene expression. We show that the predicted TetR family transcriptional …

Factors Influencing Topotecan Cns Penetration In Mouse Models, Jun Shen

Theses and Dissertations (ETD)

Camptothecin analogs such as topotecan are currently tested in clinical trials for brain tumors. However the clinical outcome is far below the expectations, which are derived from the promising preclinical studies. This discrepancy could be partially attributed to the presence of two barrier systems in the brain, the blood brain barrier (BBB) and blood cerebrospinal fluid (CSF) barrier (BCB). Further investigations have demonstrated multiple ATP-binding cassette (ABC) transporters are present at the two barriers. Camptothecin analogs are well known substrates for several of the transporters. This work defined the role of two ABC transporters, Bcrp1 and P-gp in determination of …

Effects Of Barren Reservoir On Upstream Fish Assemblages Of Barren River Tributaries, Mario Sullivan

Masters Theses & Specialist Projects

The effects of dams have long been investigated by aquatic ecologists. However, most of the research has focused on the physio-chemical changes when a lotic system is turned into a lentic system, dams as barriers to migratory fishes, and the influence of introduced species often stocked into reservoirs. It has not been until relatively recently that the upstream effects have been studied. The central theme here is that while the dam proper creates a barrier it is possible that the resulting zone of standing water may also fragment streams from an otherwise connected river system. Stream adapted species that encounter …

Longitudinal Variation In Fish Community Along The Upper Green River Below The Green River Lake, Joshua Wilsey

Masters Theses & Specialist Projects

The impoundment of flowing waters can cause decreased variation in flow and temperature, reduce habitat availability, and decreased mean temperature below a reservoir. These types of alterations can influence fish communities. Twelve sites were sampled along the Upper Green river in order to address the potential influence of impoundment on fish communities below the Green River Lake. The habitat features: mean depth, flow, dominant substrate, embeddedness, percent riffle, run and pool were measured. Temperature probes were placed at each site in order to measure temperature over an extended period of time. Backpack electrofishing and seining was used to obtain fishes. …

Coregulation Of A Neighboring Est With Rhogap, Tia Hughes

Masters Theses & Specialist Projects

It has been reported that the crossveinless-c locus of Drosophila melanogaster corresponds the RhoGAP88C gene. This determination was based on three criteria: proximity in genetic map position, complementation tests, and similarity of phenotype between RhoGAP88C RNAi constructs and the phenotype of hypomorphic cv-c' mutant homozygotes, both of which eliminate posterior crossveins (Denholm et al. 2005). There are several genes that map to this region of chromosome 3, including both RhoGAP88C, and a poorly annotated PDZ-domain containing gene corresponding to Expressed Sequence Tag (EST) Clot 13975 (approximately 60 kb upstream from the RhoGAP88C transcriptional start). A P-element insertion P[PZ]l(3)06951 is located …

Pcr-Ddge Comparison Of Fecal Bacteria From Captive And Wild Populations Of The Endangered San Esteban Island Chuckwalla (Sauromalus Varius), Tina Kelley

Masters Theses & Specialist Projects

Most modern reptiles are carnivorous or insectivorous, whereas less than 2% of the >7,800 currently recognized species are considered to be herbivorous. Of these, herbivory is confined entirely to lizards; less than 3% of known lizard species eat significant amounts of plants. Most, if not all, herbivorous animals utilize a population of symbiotic microorganisms which can break down plant structural polymers. This study analyzes the bacterial populations from fecal/uric acid deposits of wild and captive samples of the endangered, herbivorous San Esteban chuckwalla (Sauromalus varius: Iguanidae). Substrate and diet samples were also analyzed. Most studies of digestive symbionts use indirect …

Quality Assurance Of Radiation Therapy Planning Systems: Current Status And Remaining Challenges., Jacob Van Dyk

Oncology Publications

Computerized radiation therapy planning systems (RTPSs) are pivotal for treatment planning. The acceptance, commissioning, and quality control of RTPSs are uniquely complex and are described in the American Association of Physicists in Medicine Task Group Report 53 (1998) and International Atomic Energy Agency Technical Report Series No. 430 (2004). The International Atomic Energy Agency also developed a document and data package for use by vendors and purchasers to aid with acceptance testing of RTPSs. This document is based on International Electrotechnical Commission standard 62083 (2000) and describes both "type" tests to be performed in the factory and "site" tests to …

Food Restriction Compromises Immune Memory In Deer Mice (Peromyscus Maniculatus) By Reducing Spleen-Derived Antibody-Producing B Cell Numbers, Lynn B. Martin, Kristen J. Navara, Michael T. Bailey, Chelsea R. Hutch, Nicole D. Powell, John F. Sheridan, Randy J. Nelson

Integrative Biology Faculty and Staff Publications

Immune activity is variable in many wild animals, despite presumed strong selection against immune incompetence. Much variation may be due to changes in prevalence and abundance of pathogens (and/or their vectors) in time and space, but the costs of immune defenses themselves may also be important. Induction of immune activity often increases energy and protein expenditure, sometimes to the point of compromising fitness. Whether immune defenses are expensive to maintain once they are generated, however, is less well appreciated. If so, organisms would face persistent challenges of allocating resources between immunity and other expensive physiological processes, which would mandate trade-offs. …

Preparation Of Halogenated Derivatives Of Thiazolo[5,4-D]Thiazole Via Direct Electrophilic Aromatic Substitution, Vladimir Benin, Alan T. Yeates, Douglas Dudis

Chemistry Faculty Publications

Chlorination and bromination reactions of thiazolo[5,4-d]thiazole led to the generation of its mono- and dihalogenated derivatives. These are the first instances of successful direct electrophilic aromatic substitution in the thiazolo[5,4-d]thiazole ring system. X-ray analysis demonstrates that both 2-bromothiazolo[5,4-d]-thiazole and 2,5-dibromothiazolo[5,4-d]thiazole are planar structures, with strongly manifested π-stacking in the solid state. Theoretical analysis of the pyridine-catalyzed halogenation (MP2/6-31+G(d) and B3LYP/6-31+G(d)calculations) reveals that introduction of one halogen actually leads to a slightly enhanced reactivity towards further halogenation. Several halogenation mechanisms have been investigated: 1) The direct C-halogenation with N-halopyridine as electrophile; …

In Vitro Exploration Of Macrophage Migration Inhibitory Factor (Mif) As A Possible Agent Of Lymphatic Dilation In The Pathogenesis Of Lymphatic Filiariasis, Lauren Rosen

Honors Scholar Theses

Abstract:Macrophage Migration Inhibitory Factor (MIF) is a human cytokine that is well known for its role in modulating macrophage function. It has also been shown to cause smooth muscle cell death. A homolog of the MIF protein (BmMIF) has been found in Brugia malayi, one of the etiological agents of lymphatic filariasis. BmMIF shares a significant portion of its sequence homology with human MIF. Infection by Brugia malayi leads to a consistent finding of lymphatic dilation with surrounding smooth muscle cell apoptosis. We hypothesize that Brugia malayi releases BmMIF as a mediator of host smooth muscle cell death in the …

The Unfolded Protein Response Increases Production Of Pro-Angiogenic Factors By Tumor Cell Lines, Nan Liao

Theses and Dissertations (ETD)

The rapid growth and proliferation of tumor cells will be limited at a stage when they encounter inadequate levels of oxygen and nutrient supply within the poorly vascularized tumor mass. These severe conditions negatively affect the proper folding of nascent proteins in the endoplasmic reticulum (ER) and lead to accumulation of unfolded protein within ER which is referred to as ER stress. Consequently, it will trigger the unfolded protein response (UPR) signal pathway through ER membrane stress sensor proteins including activating transcription factor 6 (ATF6), inositol-requiring 1 (IRE1) and PKR-like ER localized kinase (PERK). The UPR is largely a cytoprotective …

Dietary Folate, Other B-Vitamins And Incident Alzheimer's Disease: The Cache County Memory, Health, And Aging Study, Chailyn Nelson

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

This study involves data from the Cache County Study, which began in 1994 with joined efforts by Duke University, Utah State University, and Johns Hopkins University. It consisted of 5,092 participants from Cache County, Utah, located in the northern part of the state. Characteristics of the population include high participation rates (~ 90%), a majority of participants are members of The Church of Jesus Christ of Latter-day Saints, longer life expectancy than the general US population, a greater than 80% rate of at least a high school education, and low rates of migration.

Subjects cognitive status was screened using the …

Targeted Drug Delivery Systems For Cancer Therapy, Antonio Clementi, Christine O'Connor, Mary Mcnamara, A. Mazzaglia, M. C. Aversa, A. Giuffrida

Conference Papers

The role of cyclodextrin’s (CD) in drug delivery has advanced in recent years and this may be attributed to its biocompatibility and well established synthesis. Chemical modification of CDs has shown to extend the physicochemical properties and the host capacity for a variety of drugs. β-CD has been widely used in the early stages of pharmaceutical applications because of its ready availability and its cavity size suitability for a wide range of drugs. Chemical modification of β-CD has proven to enhance aqueous solubilisation, microbiological stability and reduced toxicity in previous studies.1 Folate Receptors are over-expressed in several human cancers including …

The N-Terminal Domain Of The Y-Box Binding Protein Yb-1 Plays A Major Role In Cell Proliferation And Apoptosis, Payal Khandelwal

Theses and Dissertations (ETD)

Y-box binding protein, YB-1, is a member of the cold shock domain superfamily of proteins. It is involved in a plethora of cellular functions, including cell proliferation. The molecular mechanisms governing the involvement of YB-1 in cell proliferation are still unclear. Earlier studies done in chicken pre-B lymphocyte DT-40 cells in our laboratory have shown that a targeted disruption in one allele of chicken YB-1

(Chk-Yb-1b) gene at its N-terminal domain resulted in multiple abnormalities in the heterozygous mutants, including slower growth rate, abnormal cell morphology, increased cell size, increased genomic DNA content and significant changes in levels of cell …

The Structural And Functional Study Of Git1 Paxillin Binding Domain, Ziwei Zhang

Theses and Dissertations (ETD)

The G protein coupled receptor (GPCR)-kinase (GRK) interacting protein 1 (GIT1) is a multidomain protein that plays an important role in cell adhesion, motility, cytoskeletal remodeling, and membrane trafficking. GIT1 mediates the localization of p21-activated kinase (PAK) and PAK-interactive exchange factor (PIX) to focal adhesions, and its activation is regulated by the interaction between its C terminal paxillin-binding domain (PBD) and the LD motifs of paxillin.

In this dissertation, we determined the solution structure of rat GIT1 PBD by nuclear magnetic resonance (NMR) spectroscopy. The PBD folds into a four-helix bundle, which is structurally similar to the focal adhesion targeting …