Medicine and Health 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 …

Human Amnion As A Novel Cell Delivery Vehicle For Chondrogenic Mesenchymal Stem Cells, Tunku Kamarul Zaman

Tunku Kamarul Zaman

This study investigates the feasibility of processed human amnion (HAM) as a substrate for chondrogenic differentiation of mesenchymal stem cells (MSCs). HAM preparations processed by air drying (AD) and freeze drying (FD) underwent histological examination and MSC seeding in chondrogenic medium for 15 days. Monolayer cultures were used as control for chondrogenic differentiation and HAMs without cell seeding were used as negative control. Qualitative observations were made using scanning electron microscopy analysis and quantitative analyses were based on the sulfated glycosaminoglycans (GAG) assays performed on day 1 and day 15. Histological examination of HAM substrates before seeding revealed a smooth …

Damage To Association Fiber Tracts Impairs Recognition Of The Facial Expression Of Emotion, Carissa Philippi, Shruti Mehta, Thomas Grabowski, Ralph Adolphs, David Rudrauf

Psychology Faculty Works

No abstract provided.

Physical And Functional Coupling Of Cftr And Pde3a, Himabindu Penmatsa

Theses and Dissertations (ETD)

Formation of multiple-protein macromolecular complexes at specialized subcellular microdomains increases the specificity and efficiency of signaling in cells. In this study, we demonstrated that phosphodiesterase type 3A (PDE3A) is physically and functionally coupled to cystic fibrosis transmembrane conductance regulator (CFTR). PDE3A inhibition increases cyclic adenosine 3′, 5′-monophosphate (cAMP) levels in a compartmentalized manner at the plasma membrane, which potentiates CFTR channel function and further clusters PDE3A and CFTR into microdomains. Actin skeleton disruption reduces PDE3A-CFTR interaction; segregates PDE3A from its interacting partners thus compromise the integrity of the macromolecular complex. Consequently, PDE3A inhibition no longer activates CFTR channel function in …

Wegener's Granulomatosis: A Diagnostic Challenge, Ali Bin Sarwar Zubairi, Hammad Bin Liaquat, Shahid Javed Husain, Kulsoom Fatima

Section of Pulmonary & Critical Care

Wegener's Granulomatosis (WG) is a necrotizing granulomatous vasculitis that primarily involves small vessels in the body. Patient usually presents in the fourth to fifth decade. The clinical presentation is variable; however, majority of patients (90%) seek medical attention for nasal and sinus symptoms with or without lower respiratory symptoms of cough, dyspnoea and haemoptysis. The typical form of WG tends to involve the triad of upper and lower respiratory tract and the kidneys; while involvement of other organs like ocular, cutaneous, rheumatological, neural, gastrointestinal and lower genito-urinary tract is occasionally seen. A "limited" form with clinical findings isolated to the …

Anatomical Variations Of The Lumbar Plexus: A Descriptive Anatomy Study With Proposed Clinical Implications.Pdf, Philip A. Anloague

Philip A. Anloague

The Impact Of Left Hemisphere Stroke On Force Control With Familiar And Novel Objects: Neuroanatomic Substrates And Relationship To Apraxia, Amanda M. Dawson, Laura J. Buxbaum, Susan V. Duff

Physical Therapy Faculty Articles and Research

Fingertip force scaling for lifting objects frequently occurs in anticipation of finger contact. An ongoing question concerns the types of memories that are used to inform predictive control. Object-specific information such as weight may be stored and retrieved when previously encountered objects are lifted again. Alternatively, visual size and shape cues may provide estimates of object density each time objects are encountered. We reasoned that differences in performance with familiar versus novel objects would provide support for the former possibility. Anticipatory force production with both familiar and novel objects was assessed in six left hemisphere stroke patients, two of whom …

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 …

Parent- Versus Child-Reported Functional Health Status After The Fontan Procedure., Linda M. Lambert, L Luann Minich, Jane W. Newburger, Minmin Lu, Victoria L. Pemberton, Ellen A. Mcgrath, Andrew M. Atz, Mingfen Xu, Elizabeth Radojewski, Darlene Servedio, Brian W. Mccrindle, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: We sought to compare perceptions of functional health status between children who had undergone a Fontan procedure and their parents.

METHODS: Fontan procedure survivors 10 to 18 years of age were included in the study if the child completed the Child Health Questionnaire (CHQ) and the parent completed the parent form to assess the child's functional health status. Comparisons were made between raw domain scores for the parent- and child-completed CHQs.

RESULTS: Between March 2003 and April 2004, 1078 Fontan survivors were screened. Of the 546 eligible and consented patients, 354 were 10-18 years of age and 328 parent/child …

Chromosomal Anomalies Influence Parental Treatment Decisions In Relation To Prenatally Diagnosed Congenital Heart Disease., Sinai C. Zyblewski, Elizabeth G. Hill, Girish S. Shirali, Andrew Atz, Geoffrey Forbus, Javier Gonzalez, Anthony Hlavacek

Manuscripts, Articles, Book Chapters and Other Papers

This study aimed to identify the variables that influence parental treatment decisions after a prenatal diagnosis of congenital heart disease (CHD). The authors reviewed all cases of prenatally diagnosed structural CHD from August 1998 to December 2006 at their center. The following variables were studied as potential predictors of parental intent to treat: maternal age, race, insurance status, obstetric history, fetal gender, univentricular versus biventricular cardiac physiology, and fetal chromosomal abnormality. Uni- and multivariable logistic regression analyses were performed. In the review, 252 consecutive cases of prenatally diagnosed CHD were identified. Of these, 204 women pursued full medical treatment, whereas …

The Vesicular Acetylcholine Transporter Is Required For Neuromuscular Development And Function, Braulio M. De Castro, Xavier De Jaeger, Cristina Martins-Silva, Ricardo D. F. Lima, Ernani Amaral, Cristiane Menezes, Patricia Lima, Cintia M. L. Neves, Rita G. Pires, Thomas W. Gould, Ian Welch, Christopher Kushmerick, Cristina Guatimosim, Ivan Izquierdo, Martin Cammarota, Jane R. Rylett, Marcus V. Gomez, Marc G. Caron, Ronald W. Oppenheim, Marco A. M. Prado, Vania F. Prado

Anatomy and Cell Biology Publications

The vesicular acetylcholine (ACh) transporter (VAChT) mediates ACh storage by synaptic vesicles. However, the VAChT-independent release of ACh is believed to be important during development. Here we generated VAChT knockout mice and tested the physiological relevance of the VAChT-independent release of ACh. Homozygous VAChT knockout mice died shortly after birth, indicating that VAChT-mediated storage of ACh is essential for life. Indeed, synaptosomes obtained from brains of homozygous knockouts were incapable of releasing ACh in response to depolarization. Surprisingly, electrophysiological recordings at the skeletal-neuromuscular junction show that VAChT knockout mice present spontaneous miniature end-plate potentials with reduced amplitude and frequency, which …

Treatment Outcome Of Multi-Drug Resistant Tuberculosis In A Tertiary Care Hospital In Karachi, Nisar Ahmed Rao, Zeeshan Mahfooz, Muhammad Irfan

Section of Pulmonary & Critical Care

Objective: To assess the outcomes of pulmonary multidrug-resistant tuberculosis (MDR-TB) patients treated at Ojha Institute of Chest Diseases (OICD), a reference hospital for TB in Karachi, Pakistan. Methods: Clinical study for the period 1996-2006, with follow-up until June 2007 was performed. All the culture and sensitivity proven cases of MDR pulmonary TB were initially admitted for 3-6 months till the sputum converted negative. Treatment regimen was decided on individual basis, and included 4-6 drugs. Supervised treatment was given to all patients during the hospitalization. After discharge from the hospital, patients were followed at monthly interval at the outpatient department of …

Therapeutic Strategies Aimed To Facilitate Axonal Regeneration And Functional Recovery Following Traumatic Spinal Cord Injury, Woon Chow

Theses and Dissertations

Traumatic spinal cord injury (SCI) is a physically debilitating, emotionally devastating, financially costly, and life-changing condition that afflicts more than 1,000,000 people in the United States alone. Owing to the characteristic neuropathology and low regenerative capacity of the central nervous system, many victims of SCI are left permanently paralyzed. Though the tissue damage caused by the initial insult almost certainly cannot be reversed, intensive research in recent years to elucidate the cellular and molecular events that follows has provided new grounds for optimism. Accordingly, in this dissertation, we present a number of potential treatment strategies aimed to address some of …

Automatic Recognition Of Frog Calls Using A Multi-Stage Average Spectrum, Wen-Ping Chen, Song-Shyong Chen, Chun-Cheng Lin, Ya-Zhung Chen, Wen-Chih Lin

Bioacoustics Collection

The automatic recognition of animal sounds is one of the powerful techniques for replacing the traditional ecological survey method that mainly depends on manpower, which is hence both costly and time consuming. This study developed an automatic frog call recognition system based on the combination of a pre-classification method of the syllable lengths and a multi-stage average spectrum (MSAS) method. In this system, the input frog syllables are first classified into one of the four groups determined by the pre-classification method according to syllable length. Then the proposed MSAS method is used to extract the standard feature template to analyze …

Sleep-Disordered Breathing Affects Auditory Processing In 5–7 Year-Old Children: Evidence From Brain Recordings, Alexandra P.F. Key, Dennis L. Molfese, Louise O’Brien, David Gozal

Center for Brain, Biology, and Behavior: Faculty and Staff Publications

Poor sleep in children is associated with lower neurocognitive functioning and increased maladaptive behaviors. The current study examined the impact of snoring (the most common manifestation of sleep-disordered breathing) on cognitive and brain functioning in a sample of 35 asymptomatic children ages 5–7 years identified in the community as having habitual snoring (SDB). All participants completed polysomnographic, neurocognitive (NEPSY) and psychophysiological (ERPs to speech sounds) assessments. The results indicated that sub-clinical levels of SDB may not necessarily lead to reduced performance on standardized behavioral measures of attention and memory. However, brain indices of speech perception and discrimination (N1/P2) are sensitive …

Evaluating Diagnostic Tests—Should The Same Methods Apply?, Jenny Doust, Jonathon Craig

Jenny Doust

It is now accepted wisdom by regulators, purchasers, journal editors, and clinicians that the true effects of health care interventions can only be evaluated by well-designed randomized controlled trials. The study by Rutten et al,¹ reports the results of a randomized controlled trial of N-terminal pro-brain natriuretic peptide in an emergency department in the Netherlands. Given that this is the third randomized controlled trial assessing the effectiveness and cost effectiveness of a natriuretic peptide in an emergency department setting,²,³ it is important to ask whether diagnostic tests should always be evaluated by randomized controlled trials or are other study types …

High Aldehyde Dehydrogenase And Expression Of Cancer Stem Cell Markers Selects For Breast Cancer Cells With Enhanced Malignant And Metastatic Ability, Alysha K. Croker, David Goodale, Jenny Chu, Carl Postenka, Benjamin D. Hedley, David A. Hess, Alison L. Allan

Anatomy and Cell Biology Publications

Cancer stem cells (CSCs) have recently been identified in leukaemia and solid tumours; however, the role of CSCs in metastasis remains poorly understood. This dearth of knowledge about CSCs and metastasis is due largely to technical challenges associated with the use of primary human cancer cells in pre-clinical models of metastasis. Therefore, the objective of this study was to develop suitable pre-clinical model systems for studying stem-like cells in breast cancer metastasis, and to test the hypothesis that stem-like cells play a key role in metastatic behaviour. We assessed four different human breast cancer cell lines (MDA-MB-435, MDA-MB-231, MDA-MB-468, MCF-7) …

Comparison Of Echocardiographic And Cardiac Magnetic Resonance Imaging Measurements Of Functional Single Ventricular Volumes, Mass, And Ejection Fraction (From The Pediatric Heart Network Fontan Cross-Sectional Study)., Renee Margossian, Marcy L. Schwartz, Ashwin Prakash, Lisa Wruck, Steven D. Colan, Andrew M. Atz, Timothy J. Bradley, Mark A. Fogel, Lynne M. Hurwitz, Edward Marcus, Andrew J. Powell, Beth F. Printz, Michael D. Puchalski, Jack Rychik, Girish S. Shirali, Richard Williams, Shi-Joon Yoo, Tal Geva, Pediatric Heart Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

Assessment of the size and function of a functional single ventricle (FSV) is a key element in the management of patients after the Fontan procedure. Measurement variability of ventricular mass, volume, and ejection fraction (EF) among observers by echocardiography and cardiac magnetic resonance imaging (CMR) and their reproducibility among readers in these patients have not been described. From the 546 patients enrolled in the Pediatric Heart Network Fontan Cross-Sectional Study (mean age 11.9 +/- 3.4 years), 100 echocardiograms and 50 CMR studies were assessed for measurement reproducibility; 124 subjects with paired studies were selected for comparison between modalities. Interobserver agreement …

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."

Functional State Following The Fontan Procedure., Ismee A. Williams, Lynn A. Sleeper, Steven D. Colan, Minmin Lu, Elizabeth A. Stephenson, Jane W. Newburger, Welton M. Gersony, Meryl S. Cohen, James F. Cnota, Andrew M. Atz, Richard V. Williams, Renee Margossian, Andrew J. Powell, Mario P. Stylianou, Daphne T. Hsu, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Despite improvements in outcomes after completion of the Fontan circulation, long-term functional state varies. We sought to identify pre- and postoperative characteristics associated with overall function.

METHODS AND RESULTS: We analyzed data from 476 survivors with the Fontan circulation enrolled in the Pediatric Heart Network Fontan Cross-sectional Study. Mean age at creation of the Fontan circulation was 3.4 plus or minus 2.1 years, with a range from 0.7 to 17.5 years, and time since completion was 8.7 plus or minus 3.4 years, the range being from 1.1 to 17.3 years. We calculated a functional score for the survivors by …

Specific Levels Of Therapeutic Ultrasound Stimulate The Release Of Inflammatory And Angiogenic Mediators From Macrophages In Culture, Thomas Turner

Theses and Dissertations

Therapeutic ultrasound (TUS) is a treatment modality that is used to accelerate tissue healing. TUS is thought to affect cellular processes of tissue healing, especially those that occur in the inflammatory and early proliferative phases. TUS can be applied using various parameter selections including intensity, wavelength, duty cycle and treatment duration and no clear consensus exists on optimal parameters for healing enhancement. Macrophages are important mediators of inflammation and their actions are critical to normal progression into the proliferative phase of healing. They complete many functions during these periods of tissue healing, among those being release of cytokines and growth …

Effect Of Posture On Acromiohumeral Distance With Arm Elevation In Subjects With And Without Rotator Cuff Disease Using Ultrasonography, Nitin Kalra

Theses and Dissertations

Objectives: To examine the effects of posture on subacromial (SA) space with arm elevation in patients with rotator cuff disease (RCD) and healthy subjects. Background: Poor posture has been linked to altered scapular mechanics, theorized to lead to excessive SA space narrowing. However, no study has examined the direct effects of posture on SA space using ultrasonography. We hypothesize that when compared to a neutral posture, upright posture will increase SA space and slouched posture will decrease SA space. Methods: Subjects with painful RCD (n=31) and healthy (n=29) shoulders participated. SA space was measured on ultrasound generated images using the …

Structural Interactions Between The Α3Β1 Integrin And Mmp-2: A Potential Functional Role In Cell Adhesion, James Bowman

Theses and Dissertations

During cardiac development and in cardiac disease changes in hemodynamic load initiate events leading to remodeling of the ECM. This study addresses the hypothesis that interactions between Integrins and Metalloprotienases function to modulate cell adhesion in the cultured cardiac fibroblast. The fibroblast is positioned to detect and respond to changes in the mechanical load on the heart. Functionally the cardiac fibroblast is the primary cell type responsible for the production, maintenance, and remodeling of the cardiac interstitium. Matrix Metalloproteinases, specifically the Gelatinases, are expressed in concert during development and in disease with changes in the hemodynamic loading of the heart. …

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.

Fallow Bucks Get Hoarse: Vocal Fatigue As A Possible Signal To Conspecifics, Elisabetta Vannoni, Alan G. Mcelligott

Veterinary Science and Medicine Collection

Many studies of sexually selected vocal communication assume that calls remain stable throughout the breeding season. However, during this period, physiological and social factors change and these can have strong effects on the structure of calls and calling rates. During the rut, fallow bucks, Dama dama, reduce their feeding and increase the time and energy spent on vocalizing and fighting to gain matings, and consequently their body condition declines greatly. The availability of matings and intensity of competition between males also change. Therefore, we predicted that male vocal signalling would vary over time in response to the changing intersexual and …

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 …

Investigating The Response Of Oligodendrocyte Progenitor Cells To The Cuprizone Model Of Demyelination, David Moffatt

Theses and Dissertations

Multiple sclerosis and other myelin diseases affect the quality of life many people. In the United States alone, multiple sclerosis afflicts as many as 400,000 individuals. Myelin, which is attacked by multiple sclerosis, plays a critical role in maintaining the healthy function of the adult nervous system. There are many model systems that study myelin and its formation and loss. Our lab investigates the cuprizone model of demyelination and remyelination. The cuprizone model is commonly believed only to affect adult oligodendrocytes, which it kills. The current study investigates whether other cells in the oligodendrocyte line, such as oligodendrocyte progenitor cells, …

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 …

Fetal Cocaine Exposure Causes Epigenetic Changes In The Rat Heart, Kurt D. Meyer

Loma Linda University Electronic Theses, Dissertations & Projects

Cocaine abuse continues to be prevalent in the United States and other industrialized nations, in addition to the negative health effects that cocaine abuse has on the user, a mother who uses cocaine while pregnant also exposes the developing fetus to cocaine. Although there have been many studies of the effects of cocaine on the adult heart, studies of cocaine on the fetal heart and its potential delayed pathophysiological effects on cardiac function in adult offspring are extremely limited. The studies of the present project sought to enhance the understanding of the effect of cocaine exposure on the fetal heart …