Medical Sciences Commons^™

Gbdr Regulates Pseudomonas Aeruginosa Plch And Pchp Transcription In Response To Choline Catabolites, Matthew J. Wargo, Tiffany C. Ho, Maegan J. Gross, Laurie A. Whittaker, Deborah A. Hogan

Dartmouth Scholarship

Pseudomonas aeruginosa hemolytic phospholipase C, PlcH, can degrade phosphatidylcholine (PC) and sphingomyelin in eukaryotic cell membranes and extracellular PC in lung surfactant. Numerous studies implicate PlcH in P. aeruginosa virulence. The phosphorylcholine released by PlcH activity on phospholipids is hydrolyzed by a periplasmic phosphorylcholine phosphatase, PchP. Both plcH gene expression and PchP enzyme activity are positively regulated by phosphorylcholine degradation products, including glycine betaine. Here we report that the induction of plcH and pchP transcription by glycine betaine is mediated by GbdR, an AraC family transcription factor. Mutants that lack gbdR are unable to induce plcH and pchP in media …

Levels Of The Secreted Vibrio Cholerae Attachment Factor Gbpa Are Modulated By Quorum-Sensing-Induced Proteolysis, Brooke A. Jude, Raquel M. Martinez, Karen Skorupski, Ronald K. Taylor

Dartmouth Scholarship

Vibrio cholerae is the etiologic agent of cholera in humans. Intestinal colonization occurs in a stepwise fashion, initiating with attachment to the small intestinal epithelium. This attachment is followed by expression of the toxin-coregulated pilus, microcolony formation, and cholera toxin (CT) production. We have recently characterized a secreted attachment factor, GlcNAc binding protein A (GbpA), which functions in attachment to environmental chitin sources as well as to intestinal substrates. Studies have been initiated to define the regulatory network involved in GbpA induction. At low cell density, GbpA was detected in the culture supernatant of all wild-type (WT) strains examined. In …

Performance Of A Hip Protector Depends On Its Position During A Fall, Woochol J. Choi, Joaquin A. Hoffer, Stephen N. Robinovitch

Physical Therapy Faculty Articles and Research

"Hip protectors are designed to attenuate and redistribute the force applied to the hip region during a fall, and thereby reduce risk for hip fracture [1]. However, little information exists on the effectiveness of hip protectors in achieving these goals, and how this is altered by displacement of the hip protector relative to the greater trochanter (GT). In the current study, we tested these issues."

Nanofiber Scaffolds With Gradations In Mineral Content For Mimicking The Tendon-To-Bone Insertion Site, Xiaoran Li, Jingwei Xie, Justin Lipner, Xiaoyan Yuan, Stavros Thomopoulos, Younan Xia

MIIR Faculty Research

We have demonstrated a simple and versatile method for generating a continuously graded, bonelike calcium phosphate coating on a nonwoven mat of electrospun nanofibers. A linear gradient in calcium phosphate content could be achieved across the surface of the nanofiber mat. The gradient had functional consequences with regard to stiffness and biological activity. Specifically, the gradient in mineral content resulted in a gradient in the stiffness of the scaffold and further influenced the activity of mouse preosteoblast MC3T3 cells. This new class of nanofiberbased scaffolds can potentially be employed for repairing the tendon-to-bone insertion site via a tissue engineering approach.

Community Acquired Pneumonia: Risk Factors Associated With Mortality In A Tertiary Care Hospitalized Patients, Muhammad Irfan, Syed Fayyaz Hussain, Khubaib Mapara, Shafia Memon, Mohammed Mogri, Muniza Bana, Amna Malik, Sara Khan, Nadia A Khan

Section of Pulmonary & Critical Care

OBJECTIVE: To evaluate risk factors associated with mortality in patients hospitalized with CommunityAcquired Pneumonia (CAP) from a developing country.

METHODS: An observational study was conducted on adult patients admitted with a diagnosis of CAP from January 2002 to August 2003 at Aga Khan University hospital, Karachi, Pakistan. Clinical records were reviewed for demographic characteristics, clinical and laboratory features, hospital course, and risk factors associated with mortality.

RESULTS: A total of 329 patients (187 males) were admitted with CAP. Two-third of patients had underlying co-morbid medical illnesses. Complications developed in 15.7% cases and the overall mortality rate was 11%. Risk factors …

Il-9 As A Mediator Of Th17-Driven Inflammatory Disease, Elizabeth C. Nowak, Casey T. Weaver, Henrietta Turner, Sakhina Begum-Haque, Burkhard Becher, Bettina Schreiner, Anthony J. Coyle, Lloyd H. Kasper, Randolph J. Noelle

Dartmouth Scholarship

We report that like other T cells cultured in the presence of transforming growth factor (TGF) beta, Th17 cells also produce interleukin (IL) 9. Th17 cells generated in vitro with IL-6 and TGF-beta as well as purified ex vivo Th17 cells both produced IL-9. To determine if IL-9 has functional consequences in Th17-mediated inflammatory disease, we evaluated the role of IL-9 in the development and progression of experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis. The data show that IL-9 neutralization and IL-9 receptor deficiency attenuates disease, and this correlates with decreases in Th17 cells and IL-6-producing macrophages in …

Field Testing Adolescent Females For Cardiovascular Disease Risk, C. Jayne Brahler, Wesley R. Stephens, Betsy Donahoe Fillmore

Physical Therapy Faculty Publications

Over-fatness and poor cardiovascular (CV) fitness are well-documented risk factors for cardiovascular disease (CVD) in adults, but less is known about their association with disease risk in adolescents. This study aimed to determine the relationship between anthropometrics, fitness, and CVD risk.

Six anthropometric indicators of body fatness, seven measures of fitness, and seven metabolic and hemodynamic CVD risk factors were measured in a convenience sample of 28 female high school students (15-18 years of age). A tally was made of the number of factors for which each subject was outside the normal reference range (CVD risk).

Correlation analyses were completed …

Multiscale Genomic Analysis Of The Corticolimbic System: Uncovering The Molecular And Anatomic Substrates Of Anxiety-Related Behavior, Khyobeni Mozhui

Theses and Dissertations (ETD)

Genetic diversity generates variation at multiple phenotypic levels, ranging from the most basic molecular to higher-order cognitive and behavioral traits. The far-reaching impact that genes have on higher traits is apparent in several neuropsychiatric conditions such as stress and anxiety disorders. Like most, if not all, neural phenotypes, stress, anxiety, and other emotion-related traits are extremely complex and are defined by the interplay of multiple genetic, environmental, experiential, and epigenetic factors.

The work presented in this dissertation is a multi-scalar, integrative analysis of the molecular and neuroanatomic substrates that underlie emotion-related behavior. The amygdala is a principle component of the …

Paracrine Sonic Hedgehog Signalling By Prostate Cancer Cells Induces Osteoblast Differentiation, Samantha M Zunich, Taneka Douglas, Maria Valdovinos, Tiffany Chang

Dartmouth Scholarship

Sonic hedgehog (Shh) and components of its signalling pathway have been identified in human prostate carcinoma and increased levels of their expression appear to correlate with disease progression and metastasis. The mechanism through which Shh signalling could promote metastasis in bone, the most common site for prostate carcinoma metastasis, has not yet been investigated. The present study determined the effect of Shh signalling between prostate cancer cells and pre-osteoblasts on osteoblast differentiation, a requisite process for new bone formation that characterizes prostate carcinoma metastasis.

Detection Of Viruses In Human Adenoid Tissues By Use Of Multiplex Pcr, Masatoki Sato, Haijing Li, Mine R. Ikizler, Jay A. Werkhaven, John V. Williams, James D. Chappell, Yi-Wei Tang, Peter F. Wright

Dartmouth Scholarship

By PCR, we detected a high frequency of viruses in adenoids obtained from children without acute respiratory symptoms. Our results suggest that persistent/latent viral infection in the respiratory tract confounds interpretation of the association of pathogen detection by PCR with acute respiratory infection in these sources.

Role Of Cyclophilin D In Secondary Spinal Cord And Brain Injury, Jordan Mills Clark

University of Kentucky Doctoral Dissertations

In the hours and days following acute CNS injury, a secondary wave of events is initiated that exacerbate spinal tissue damage and neuronal cell death. A potential mechanism driving these secondary events is opening of the mitochondrial permeability transition pore (mPTP) and subsequent release of several cell death proteins. Previous studies have shown that inhibition of cyclophilin D(CypD), the key regulating component in mPTP opening, was protective against insults that induce necrotic cell death. We therefore hypothesized that CypD-null mice would show improved functional and pathological outcomes following spinal cord injury (SCI) and traumatic brain injury (TBI). Moderate and severe …

Glutamate Regulation In The Hippocampal Trisynaptic Pathway In Aging And Status Epilepticus, Michelle Lee Stephens

University of Kentucky Doctoral Dissertations

A positive correlation exists between increasing age and the incidence of hippocampal-associated dysfunction and disease. Normal L-glutamate neurotransmission is absolutely critical for hippocampal function, while abnormal glutamate neurotransmission has been implicated in many neurodegenerative diseases. Previous studies, overwhelmingly utilizing ex vivo methods, have filled the literature with contradicting reports about hippocampal glutamate regulation during aging. For our studies, enzyme-based ceramic microelectrode arrays (MEA) were used for rapid (2 Hz) measurements of extracellular glutamate in the hippocampal trisynaptic pathway of young (3-6 months), late-middle aged (18 mo.) and aged (24 mo.) urethane-anesthetized Fischer 344 rats. Compared to young animals, glutamate terminals …

Control Of Myosin Motor Activity And Actin Filament Translation By Alteration Of Assay Reducing Potential, Siva Krishna Nalabotu

Theses, Dissertations and Capstones

The use of biomolecular motors for nanotechnological applications has been impaired by an inability to control biomolecular motor activity in a temporal fashion. Previous data has suggested that myosin activity can be modulated by inducing changes in the degree of myosin oxidation. The hypothesis of this study is that myosin motor activity can be regulated by altering the amount of antioxidants and reducing agents present in assay solution. To test this hypothesis we systematically altered the concentration of reducing agents and examined the effects of these changes on myosin-dependent actin filament translation. Our findings indicate that myosin activity can be …

Loss Of Ski Expression In Testicular Cancer Leads To An Enhanced Invasive Phenotype Through Both Bmp-Dependent And Bmp-Independent Pathways, Amy N. Nash

Theses, Dissertations and Capstones

The proto-oncogene SKI is a transcription factor and a co-repressor of the TGFβ superfamily, including TGF

β and BMP. However, additional data suggests that SKI may function as a tumor suppressor in some cell types. The TGFβ superfamily has been implicated in cancer progression and germ cell migration. Testicular cancer afflicts men during their peak reproductive years and is the most common cancer among men of this age group. Cisplatin-based chemotherapy is the standard treatment for testicular cancer. This treatment can lead to undesirable side effects, including infertility. We have shown that SKI expression is decreased in testicular germ cell …

Liquid Chromatography-Tandem Mass Spectrometry For The Determination Of Methylprednisolone In Rat Plasma And Liver After Intravenous Administration Of Its Liver-Targeted Dextran Prodrug, Shuang-Qing Zhang, Helen R. Thorsheim, Suman Penugonda, Venkateswaran C. Pillai, Quentin R. Smith, Reza Mehvar

Pharmacy Faculty Articles and Research

A specific and sensitive liquid chromatography (LC)-tandem mass spectrometric method for quantitative determination of methylprednisolone (MP) in rat plasma and liver was developed and validated using triamcinolone acetonide as an internal standard. Liquid-liquid extraction using tert-butyl methyl ether was used to extract the drug and the internal standard from plasma and liver. The separation of MP was performed on a C(18) column with a mobile phase of acetonitrile:0.5% formic acid aqueous solution (85:15, v/v) over 4 min. The assay was based on the selected reaction monitoring transitions at m/z 375 -> 161 for MP in plasma, 375 -> 357 for …