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Pancreatic Ribonuclease Functions As An Epidermal Growth Factor Receptor Ligand Independently Of Its Enzyme Activity And Contributes To Cetuximab Resistance, Heng-Huan Lee

Dissertations and Theses (Open Access)

Ribonuclease (RNase) with its catalytic enzyme activity to degrade RNAs has been shown as a diagnostic serum marker for pancreatic cancer and has also been suspected to have an unidentified cell surface receptor. Epidermal growth factor receptor (EGFR), a well-characterized receptor tyrosine kinase is an effective therapeutic target in multiple cancer types. However, clinical trials targeting EGFR have not demonstrated improved therapeutic efficacy in pancreatic cancer. Here, we show that both bovine pancreatic RNase A (bRNaseA) and human RNase 5 (hRNase5) act as EGFR ligands and directly activate EGFR to promote epithelial-mesenchymal transition. This ligand-like activity is independent of RNases’ …

Egfr Modulates Microrna Maturation In Response To Hypoxia Through Phosphorylation Of Argonaute2, Jia Shen

Dissertations and Theses (Open Access)

MicroRNAs (miRNAs) are generated by two-step processing to yield small RNAs that negatively regulate target gene expression at posttranscriptional level. Deregulation of miRNAs has been linked to diverse pathological processes, including cancer. Recent studies have also implicated miRNAs in regulatory roles to cope with a spectrum of stresses, such as hypoxia, which is frequently encountered in the poorly angiogenic core of a solid tumor. However, the upstream regulators of miRNA biogenesis machineries remain obscure, raising the question of how tumor cells efficiently coordinate and impose specificity on miRNA expression and function in response to stresses. Here, we show that EGFR, …

Nuclear Translocation Of Met Via Internet Mechanism, Mei-Kuang Chen

Dissertations and Theses (Open Access)

MET is one of the receptor tyrosine kinases (RTKs) that are overexpressed in malignant cancer types, including breast cancer. While RTKs are traditionally known for their roles in signaling transduction from the cell surface, recent studies have provided evidence demonstrating that most of RTKs can translocate into nucleus to regulate cellular processes in response to both ligand and stress stimulation. Oxidative stress is a common stress in cancer cells due to alteration of metabolism, and constitutive oxidative stress related to reactive oxygen species (ROS) has been observed in breast cancer cells. Here, we show that hepatocyte growth factor (HGF) as …

Genomic Characterization Of Polyps In Familial Adenomatous Polyposis Patients And Identification Of Candidate Chemopreventive Drugs, Francis A. San Lucas

Dissertations and Theses (Open Access)

Familial adenomatous polyposis (FAP) is an autosomal dominant disease characterized by APC germline mutations and the development of hundreds to thousands of premalignant adenomas in the gastrointestinal tract at a young age. If left untreated, these patients inevitably develop colon cancer (CRC) and small bowel tumors. We performed exome sequencing of samples from 12 FAP patients to characterize adenomas and to identify candidate genes of adenoma development that may serve as potential targets for chemoprevention drug development. From each patient, a blood and at least one polyp were sequenced with a total of 25 polyps analyzed. In some cases, normal …

Discovery And Elucidation Of The Fgfr3-Tacc3 Recurrent Fusion In Glioblastoma, Brittany C. Parker Kerrigan

Dissertations and Theses (Open Access)

Fusion genes occur due to chromosomal instability where two previously separate genes rearrange and fuse together, forming a hybrid gene. The first fusions were reported in leukemias; however, with the advent of more powerful sequencing technologies, fusions have recently been reported in several solid tumors. Using next-generation deep sequencing approaches, we discovered a fusion gene connecting the fibroblast growth factor receptor 3 (FGFR3) gene to the transforming coiled-coil containing protein 3 (TACC3) gene in glioblastoma multiforme. The fusion occurred in 8.3% of patient samples, but not in low grade or normal samples. FGFR3-TACC3 produced an in-frame …

Stochastic Data Assimilation Approaches For Magnetic Resonance Temperature Imaging, Joshua P. Yung

Dissertations and Theses (Open Access)

During magnetic resonance (MR)-guided thermal therapies, proton resonance frequency shift (PRFS) based MR temperature imaging can quantitatively monitor tissue temperature changes. It is widely known that the PRFS technique is easily perturbed by tissue motion, tissue susceptibility changes, magnetic field drift, and modality–dependent applicator induced artifacts. Due to recent advances in computational algorithms and hardware, much more powerful statistical analysis methods are becoming realizable in the real-time processing environment. To this end, my dissertation research focused on the development, validation, and implementation of stochastic data-driven processing techniques to increase the robustness of MR temperature monitoring during thermal therapies. MR temperature …

Use Of Oversized Injectable Valves In Growing Children For Total Repair Of Right Ventricular Outflow Tract Anomalies (Preliminary Results), Luca Deorsola, Pietro Angelo Abbruzzese

The Texas Heart Institute Journal

Right ventricular outflow tract surgery was originally confined to transannular patching, in the belief that pulmonary regurgitation was well tolerated. Because follow-up evaluations revealed the deleterious effects of pulmonary regurgitation, surgery today aims to spare or replace the valve. Available replacement devices have short lifetimes, considering growth mismatch in children. We hypothesize that oversizing the right infundibulum anticipates growth and that a squeezed prosthesis can complete the expansion process.

The No-React® Injectable BioPulmonic Valve is designed for right infundibular surgery in adults, and hundreds of implants have shown promising results. We used this device for surgery in babies, with the …

The In-Hospital Consultation Today: Whom Does It Best Serve?, Herbert L Fred

The Texas Heart Institute Journal

No abstract provided.

Nontyphoidal Cardiac Salmonellosis: Two Case Reports And A Review Of The Literature, Daniel Ortiz, Eric M Siegal, Christopher Kramer, Bijoy K Khandheria, Ernesto Brauer

The Texas Heart Institute Journal

Nontyphoidal Salmonella, especially Salmonella enterica, is a rare cause of endocarditis and pericarditis that carries a high mortality rate. Proposed predisposing conditions include immunodeficiency states, congenital heart defects, and cardiac valve diseases. We present 2 cases of cardiovascular salmonellosis. The first case is that of a 73-year-old woman with mechanical mitral and bioprosthetic aortic valves who died from sequelae of nontyphoidal Salmonella mitral valve vegetation, aortic valve abscess, and sepsis. The second case is that of a 62-year-old man with a recent systemic lupus erythematosus exacerbation treated with oral steroids, who presented with obstructive features of tamponade and sepsis secondary …

Right Ventricular Outflow Tract Obstruction Caused By Double-Chambered Right Ventricle Presenting In Adulthood, John Kokotsakis, Efthymia G Rouska, Leanne Harling, Hutan Ashrafian, Vania Anagnostakou, Christos Charitos, Thanos Athanasiou

The Texas Heart Institute Journal

Congenital heart diseases that cause obstruction of the right ventricular outflow tract are often difficult to diagnose. We report the case of a 49-year-old man who presented with long-standing shortness of breath on exertion. Imaging revealed right ventricular outflow tract obstruction caused by a double-chambered right ventricle, and he was referred for surgical correction. This case emphasizes both the detailed perioperative evaluation that is needed when diagnosing adults who present with manifestations of congenital heart disease and a method of successful surgical correction that resulted in symptom resolution.

Global Burden Of Disease Study 2010: Interpretation And Implications For The Neglected Tropical Diseases, Ian Bolliger, Et Al.

Faculty, Staff and Students Publications

No abstract provided.

Spontaneous Coronary Artery Dissection (Scad): New Insights Into This Not-So-Rare Condition, Sharonne N Hayes

The Texas Heart Institute Journal

No abstract provided.

Natural Progression Of Low-Gradient Severe Aortic Stenosis With Preserved Ejection Fraction, Antony Leslie Innasimuthu, Sanjay Kumar, Jason Lazar, William E Katz

The Texas Heart Institute Journal

Because the natural progression of low-gradient aortic stenosis (LGAS) has not been well defined, we performed a retrospective study of 116 consecutive patients with aortic stenosis who had undergone follow-up echocardiography at a median interval of 698 days (range, 371–1,020 d). All patients had preserved left ventricular ejection fraction (>0.50) during and after follow-up.

At baseline, patients were classified by aortic valve area (AVA) as having mild stenosis (≥1.5 cm2), moderate stenosis (≥1 to <1.5 cm2), or severe stenosis (<1 cm2). Severe aortic stenosis was further classified by mean gradient (LGAS, mean <40 mmHg; high-gradient aortic stenosis [HGAS], mean ≥40 mmHg). We compared baseline and follow-up values among 4 groups: patients with mild stenosis, moderate stenosis, LGAS, and HGAS.

At baseline, 30 patients had mild stenosis, 54 had moderate stenosis, 24 had LGAS, and 8 had HGAS. Compared with the moderate group, the LGAS …

Exertional Dyspnea As A Symptom Of Infrarenal Aortic Occlusive Disease, Stacey L Schott, Fernanda Porto Carreiro, James R Harkness, Mahmoud B Malas, Stephen M Sozio, Sammy Zakaria

The Texas Heart Institute Journal

Advanced atherosclerosis of the aorta can cause severe ischemia in the kidneys, refractory hypertension, and claudication. However, no previous reports have clearly associated infrarenal aortic stenosis with shortness of breath. A 77-year-old woman with hypertension and hyperlipidemia presented with exertional dyspnea. Despite extensive testing and observation, no apparent cause for this patient's dyspnea was found. Images revealed severe infrarenal aortic stenosis. After the patient underwent stenting of the aortic occlusion, she had immediate symptomatic improvement and complete resolution of her dyspnea within one month. Twelve months after vascular intervention, the patient remained asymptomatic. In view of the distinct and lasting …

Sex-Specific Biatrial Volumetric Measurements Obtained With Use Of Multidetector Computed Tomography In Subjects With And Without Coronary Artery Disease, Matthew J Budoff, Sandeep R Pagali, Yasmin S Hamirani, Andy Chen, Gordon Cheu, Yanlin Gao, Dong Li, Songshou Mao

The Texas Heart Institute Journal

Atrial volumetric measurement has proven clinical implications. Advances in cardiac imaging, notably the precision enabled by multidetector computed tomography (MDCT), herald the need for new criteria of what constitutes normal volumetric measurements. With use of 64-slice MDCT, we compared the atrial volumes in healthy individuals with those in individuals with coronary artery disease.

By means of manual segmentation, we measured biatrial volume in 686 participants who underwent retrospective electrocardiographic-gated MDCT angiographic evaluation. The study population included a control group of 203 persons with no cardiac abnormalities, and a study group of 483 patients with obstructive coronary artery disease. All variables …

Outpatient Management Of Heart Failure In The United States, 2006-2008, Kailash Mosalpuria, Sunil K Agarwal, Sirin Yaemsiri, Bredy Pierre-Louis, Samir Saba, Rene Alvarez, Stuart D Russell

The Texas Heart Institute Journal

Better outpatient management of heart failure might improve outcomes and reduce the number of rehospitalizations. This study describes recent outpatient heart-failure management in the United States.

We analyzed data from the National Ambulatory Medical Care Survey of 2006–2008, a multistage random sampling of non-Federal physician offices and hospital outpatient departments.

Annually, 1.7% of all outpatient visits were for heart failure (51% females and 77% non-Hispanic whites; mean age, 73 ± 0.5 yr). Typical comorbidities were hypertension (62%), hyperlipidemia (36%), diabetes mellitus (35%), and ischemic heart disease (29%). Body weight and blood pressure were recorded in about 80% of visits, and …

Youth Voices: Performance Poetry As A Platform For Literacy, Creativity, And Civic Engagement, Emanuelee "Outspoken" Bean, Kate Rybka Brennan

Journal of Applied Research on Children: Informing Policy for Children at Risk

The youth slam poetry movement is growing in Houston. Writers in the Schools (WITS) is helping youth explore their truths through performance poetry and the renowned Meta-Four Houston program. Spoken word, slam competitions, and performance poetry bring people together to share stories and listen to our tomorrows. Performance poetry encourages creative self-expression and literacy among youth, while building a literary culture and platform for social change. By teaching youth to own their words, they learn to understand the potential power of their ideas. Performance poetry is a strong vehicle for education, deepening literacy, creativity, and communication skills, while preparing students …

Informing Parent Targeted Interventions To Promote Increased Physical Activity Among Youth, Teresia O'Connor

Journal of Applied Research on Children: Informing Policy for Children at Risk

Invited Commentary on "Examining the Disconnect Between Parents' Perceptions and Reality Regarding the Physical Activity Levels of Their Children."

Contact In Foster Care: Bridge Or Collision Between Two Worlds?, João M. S. Carvalho, Paulo Delgado

Journal of Applied Research on Children: Informing Policy for Children at Risk

This study aims not only to analyze the contact in foster care in Portugal compared to results collected from other studies but also to define the implications of its practice so as to propose improvements to the child protection system. It involves 289 foster children from the District of Porto whose results were obtained from official records. Subsequently, this study discusses the insights and practical consequences, the importance of maintaining up-to-date information on the changes of the biological family, the need to improve specific skills in social workers, and how to overlook the negative results of visits regarding the advantages …

Examining The Potential Disconnect Between Parents’ Perceptions And Reality Regarding The Physical Activity Levels Of Their Children, Guy Faulkner, Vaeda Solomon, Tanya Berry, Sameer Deshpande, Amy E. Latimer-Cheung, Ryan Rhodes, John Spence, Mark S. Tremblay

Journal of Applied Research on Children: Informing Policy for Children at Risk

Background: Parental support plays an important role in facilitating the participation of children in physical activity. However, there is evidence that parents overestimate their child’s level of physical activity – this may lead to inaction in promotion attempts by parents. This potential disconnect between parental perceptions and reality was recently the focus of the ‘Think Again’ social marketing campaign developed by PartipACTION.

Purpose: To qualitatively explore parents’ perceptions of the Think Again advertisements, and the possible disconnect between perceptions and reality regarding their children’s physical activity levels.

Method: Semi-structured interviews were conducted with 12 mothers and 12 fathers of children …

Early Lessons Learned From Building Local Early Childhood Comprehensive Systems In Texas, Cynthia Osborne, Kaeley C. Bobbitt, Jill M. Boelter, Tracy K. Ayrhart

Journal of Applied Research on Children: Informing Policy for Children at Risk

In 2010, the Maternal, Infant, and Early Childhood Home Visiting Program (MIECHV), provided states with the opportunity to apply for funding to build and expand evidence-based home visiting programs in their states and to incorporate community collaboration components, referred to as early childhood comprehensive systems (ECCS). For Texas, this was the first opportunity to build a statewide program of home visiting services that would be incorporated within local comprehensive early childhood systems to support the early development of Texas children and their families. This paper highlights the lessons learned from the first year of implementing a comprehensive system of early …

Project Passport: An Integrated Group-Centered Approach Targeting Pregnant Teens And Their Partners, Ruth S. Buzi, Peggy B. Smith, Constance M. Wiemann, Melissa F. Peskin, Mariam R. Chacko, Claudia Kozinetz A.

Journal of Applied Research on Children: Informing Policy for Children at Risk

Objective: To describes the development of Project Passport, a perinatal intervention designed to reduce negative outcomes among pregnant teens. Methods: A logic model guided the planning, development and evaluation plan for the intervention. It included the selection of health goals, behaviors to be targeted, determinants of the selected behaviors, and activities to impact each selected determinant. Results: The process resulted in the formulation of an intervention that incorporates CenteringPregnancy, a group model of prenatal care, Positive Youth Development components, and male involvement. The evaluation examines the effectiveness of the intervention in enhancing health, educational and psychosocial outcomes among …

Using Live Coaching And Video Feedback To Teach Responsive Parenting Skills: Experience From The Pals Project, Cathy L. Guttentag

Journal of Applied Research on Children: Informing Policy for Children at Risk

Children living in poverty or born to teenage parents are at increased risk for developmental delays as well as child neglect. Research has shown that one effective avenue for preventive intervention is teaching parents to recognize and respond to their young children’s communicative signals using responsive caregiving behaviors (e.g., warmth and praise, prompt responses linked contingently to the child’s signals, following the child’s interest, stimulating language, and using positive behavior guidance strategies). However, parents with low education and literacy levels are often limited in the degree to which they can benefit from generic instructional materials such as parenting books and …

The Prevention Of Child Physical Abuse And Neglect: An Update, Geoffrey Nelson, Rachel Caplan

Journal of Applied Research on Children: Informing Policy for Children at Risk

We reviewed research that has evaluated prevention programs for child abuse and neglect. A few universal educational and parenting programs (e.g., abusive head trauma educational programs, enhanced pediatric care interventions) have been found to be effective. Moreover, a few selective home visitation programs (e.g., the Nurse-Family Partnership program), have shown evidence that they can prevent child abuse and neglect. As well, there is some evidence that multi-component programs are successful. Finally, the research on the importance of program length and intensity as a moderator of program effectiveness is mixed. While the evidence base of effective prevention programs for child abuse …

Family Well-Being: A Complex Challenge Worth Pursuing, Susan H. Landry

Journal of Applied Research on Children: Informing Policy for Children at Risk

Issue Editor, Susan Landry's point of view and summary of the articles in Family Well-Being and Social Environments.

Evaluation Of Artifacts In Experimental Cine 4d Ct Acquisition Methods, Sarah Joy

Dissertations and Theses (Open Access)

Four-dimensional computed tomography (4D CT) has increased the accuracy of radiation treatment planning for patients in whom the extent of target motion is large. 4D CT has become a standard of care for radiation treatment simulation, allowing decreased motion artifacts and increased spatiotemporal localization of anatomical structures that move. However, motion artifacts may still remain. These artifacts, or artificial anatomic spatial distributions, add a systematic uncertainty to the treatment process and limit the accuracy of lung function images derived from CT. We proposed to reduce the motion artifacts in cine 4D CT by using three novel investigational 4D CT acquisition …

Factors Associated With Physical Activity In Kindergarten Children, Carol Hammonds

Dissertations and Theses (Open Access)

Background: Reversing obesity is an urgent public health need for children: worldwide, in 2011 more than 40 million children under the age of five were either overweight or obese. Increasing intensity and duration of physical activity is a strategy to aid in preventing and reducing obesity. A minimum of 60 minutes per day of moderate to vigorous physical activity is recommended for children. School settings, such as full-day kindergarten, where 74% of children in the United States are enrolled, provide opportunities for population-based interventions to increase physical activity, yet little objective data exist on current levels of physical activity in …

How Do Black Nulliparous Women Cognitively Construct Birth?, Marianne F. Moore

Dissertations and Theses (Open Access)

A focused ethnography was conducted to determine the cognitive constructions about birth described by nulliparous Black women in an urban area of the Southwestern US; also, during postpartum, how do these women reconcile expectations with the actual birth? Semi-structured interviews were conducted before birth and after birth.

Women, 16 or older, 17 - 33 weeks carrying a singleton fetus and without anomalies or problems like pre-gestational diabetes, NYHA Cardiac Class III/IV, cancer, renal failure, or sickle cell anemia that eliminated vaginal birth were sequentially recruited and sampled in an affiliated ultrasound clinic. Women scheduled for an anatomy scan were approached. …

Understanding The "Big Picture": End-Of-Life Decisions In The Picu, Amy J. Howells

Dissertations and Theses (Open Access)

Objective: Describe critical care providers' cognitive constructions or their interpretation of the process of decision-making that influences both the technique of conversations and the recommendations given to parents regarding limitation or withdrawal of life sustaining treatments from terminally ill children in the PICU. Design: Qualitative Medical Ethnography. Setting: Tertiary care children's hospital affiliated with a college of medicine. Participants: Eleven critical care providers in the department of pediatrics (attending physicians, critical care fellows, pediatric nurse practitioners, physician assistants). Interventions: In depth, semi-structured interviews designed to explore the experiences of providers in the participation of end-of-life care decision-making. Measurements and Main …

Modulated Functions Of The Fanconi Anemia Core Complex, Yaling Huang

Dissertations and Theses (Open Access)

Cells derived from Fanconi anemia (FA) patients are characterized by hypersensitivity to DNA interstrand crosslinks (ICLs), suggesting that FA genes play a role in ICL repair. Fanconi anemia core complex (including A, B, C, E, F, G, L, FAAP20, and FAAP100) activates the Fanconi pathway by providing the essential E3 ligase activity for FANCD2 mono-ubiquitination. Previous studies suggested the existence of three protein-protein interaction groups. However, the functions of most FA core complex protein are still limited to their presence in the complex. How the spatially-defined FANCD2 ubiquitination is accomplished by the core complex remains unknown.

To elucidate the roles …