Digital Commons Network^™

Spinal Cord Protection: Lessons Learned From Endovascular Repair, Jennifer N Dulin, Meredith L Moore, Kevin W Gates, Joanna H Queen, Raymond J Grill

Faculty, Staff and Student Publications

There is a high incidence of infertility in males following traumatic spinal cord injury (SCI). Quality of semen is frequently poor in these patients, but the pathophysiological mechanism(s) causing this are not known. Blood-testis barrier (BTB) integrity following SCI has not previously been examined. The objective of this study was to characterize the effects of spinal contusion injury on the BTB in the rat. 63 adult, male Sprague Dawley rats received SCI (n = 28), laminectomy only (n = 7) or served as uninjured, age-matched controls (n = 28). Using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), BTB permeability to the …

Cardiac Dysfunction After Cancer Treatment, Michael S Ewer, Sandra M Swain, Daniela Cardinale, Anecita Fadol, Thomas M Suter

The Texas Heart Institute Journal

Onco-cardiology is an evolving discipline that requires the consideration of cardiotoxicity in preclinical, clinical,and therapeutic aspects of protocol development,treatment, and surveillance of patients who have undergone interventions using cardiotoxic agents. Only then can we foster new ways to maximize survival while keeping cardiac damage within acceptable limits. It is to this end that our working together has brought us to our present understanding. In the future, we may expect onco-cardiology to play an even greater role in the care of cancer patients.

Usefulness Of The Echocardiographic Multi-Parameter Score (Emps) In Evaluating Left Ventricular Global Heart Function, Bingyuan Zhou, Junhua Yang, Xiangjun Yang, Yongming He, Caiming Zhao, Sudan Xu, Huifeng Wang

The Texas Heart Institute Journal

In this study, we established a new index by combining several echocardiographic parameters to quantify heart failure. We selected 233 consecutive patients who underwent both echocardiographic and plasma B-type natriuretic peptide (BNP) tests within 24 hours after referral for suspected heart failure. The echocardiographic parameters included systolic function, diastolic function, left ventricular chamber remodeling, valvular lesions, systolic pulmonary arterial pressure, and regional wall-motion abnormality. Each factor was scored from 1 to 3 points according to its severity. The total point from these 6 factors is the echocardiographic multi-parameter score (EMPS).

The EMPS for 37, 51, 77, and 38 patients from …

Rosuvastatin Therapy Does Not Affect Serum Mmp-13 Or Timp-1 Levels In Hypercholesterolemic Patients, Cihan Cevik, Kenneth Nugent, Gary Meyerrose, Mohammad Otahbachi, Cemil Izgi, Mark Lyte, R David Fish

The Texas Heart Institute Journal

Matrix metalloproteinases degrade the collagen content of atherosclerotic plaque and reduce plaque stability. In tissue sections of atherosclerotic plaque, the expression of matrix metalloproteinases is increased. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) decrease the tissue expression of matrix metalloproteinases-1, -2, -3, and -9 in atheromatous plaque by attenuating the inflammatory process that leads to increased expression. However, it is not known whether statins decrease levels of matrix metalloproteinase-13—an enzyme crucial to the initiation of collagen degradation—as part of their plaque-stabilizing effect.

We prospectively examined the effect of statin therapy on serum levels of matrix metalloproteinase-13, tissue inhibitor of metalloproteinase-1, and …

Cd34-Positive Stem Cells In The Treatment Of Heart And Vascular Disease In Human Beings, Alexander R Mackie, Douglas W Losordo

The Texas Heart Institute Journal

Bone marrow-derived CD34(+) cells are a well-characterized population of stem cells that have traditionally been used clinically to reconstitute the hematopoietic system after radiation or chemotherapy. More recently, CD34(+) cells have also been shown to induce therapeutic angiogenesis in animal models of myocardial, peripheral, and cerebral ischemia. The mechanism by which CD34(+) cells promote therapeutic angiogenesis is not completely understood, although evidence supports both direct incorporation of the cells into the expanding vasculature and paracrine secretion of angiogenic growth factors that support the developing microvasculature. Phase I and phase II clinical trials have explored the usefulness of CD34(+) cells in …

Prehypertension: A Meta-Analysis Of The Epidemiology, Risk Factors, And Predictors Of Progression, Xiaofan Guo, Liling Zou, Xingang Zhang, Jue Li, Liqiang Zheng, Zhaoqing Sun, Jian Hu, Nathan D Wong, Yingxian Sun

The Texas Heart Institute Journal

We investigated the prevalence and risk factors of prehypertension, as well as the predictors of progression from prehypertension to hypertension. To do this, we performed a systematic review and meta-analysis of cross-sectional and longitudinal studies, after unrestricted searches of PubMed and The Cochrane Library through September 2010. In addition, we reviewed references, major textbooks, and review articles. Pooled prevalence, standardized mean differences, and odds ratios were estimated by using a random-effects model.

Twenty-six articles met our inclusion criteria; these included 20 cross-sectional and 6 longitudinal studies, with a total sample of 250,741 individuals. The overall pooled prevalence of prehypertension was …

Heart Disease And Hormones, Stephanie A Coulter

The Texas Heart Institute Journal

Results from more than 40 observational studies conducted in women over 3 decades have repeatedly indicated the cardioprotective effects of postmenopausal hormone replacement therapy (HRT). Women taking estrogen in these observational trials experienced a consistent 30% to 50% reduction in cardiovascular (CV) events. The biologic benefit of estrogen has been attributed to improvements in lipid profiles and endothelial function.

A Dosing Study Of Bone Marrow Mononuclear Cells For Transendocardial Injection In A Pig Model Of Chronic Ischemic Heart Disease, Guilherme V Silva, Marlos R Fernandes, Cristiano O Cardoso, Ricardo R Sanz, Edie M Oliveira, Pilar Jimenez-Quevedo, Javier Lopez, Franca S Angeli, Yi Zheng, James T Willerson, Emerson C Perin

The Texas Heart Institute Journal

We studied the effect of the dose of bone marrow mononuclear cells, delivered via transendocardial injection, upon capillary density and fibrosis in pigs with chronic ischemic heart disease.

Pigs (n = 16) that had undergone ameroid constrictor placement (left circumflex coronary artery) to induce chronic ischemia were divided equally into 4 groups on the basis of bone marrow mononuclear cell dose: control (saline injection) and 50, 100, or 200 × 106 bone marrow mononuclear cells. Thirty days after ameroid placement, each pig received 13 transendocardial NOGA-guided injections. An implantable loop recorder monitored possible arrhythmias caused by cell transplantation. Thirty days …

Micro-Ultrasonographic Imaging Of Atherosclerotic Progression And Correlation With Inflammatory Markers In Apolipoprotein-E Knockout Mice, Rong-Juan Li, Ya Yang, Yan-Hong Wang, Jin-Jie Xie, Li Song, Zheng Wang, Yao-Zhong Zhang, Yan-Wen Qin, Zhi-An Li, Xiao-Shan Zhang

The Texas Heart Institute Journal

We studied prospectively whether atherosclerotic progression in apolipoprotein-E knockout mice could be noninvasively and accurately measured by use of high-resolution ultrasonographic biomicroscopy. We examined the correlation between the ultrasonographic characterization of ascending aortic atherosclerotic plaque and plasma C-reactive protein, interleukin-1, and interleukin-6 levels in these mice.

In 4 age groups (8, 16, 24, and 32 wk) of 8 male knockout mice each (atherosclerotic groups) and age-matched male C57BL/6 mice (control groups), we used ultrasonographic biomicroscopy to measure maximal plaque thickness or intima-media thickness in the ascending aorta. We compared the findings with corresponding histologic measurements, and we measured plasma C-reactive …

Mechanical Behavior Of Fully Expanded Commercially Available Endovascular Coronary Stents, Josip Tambaca, Suncica Canic, Mate Kosor, R David Fish, David Paniagua

The Texas Heart Institute Journal

The mechanical behavior of endovascular coronary stents influences their therapeutic efficacy. Through computational studies, researchers can analyze device performance and improve designs. We developed a 1-dimensional finite element method, net-based algorithm and used it to analyze the effects of radial loading and bending in commercially available stents. Our computational study included designs modeled on the Express, Cypher, Xience, and Palmaz stents.

We found that stents that did not fully expand were less rigid than the fully expanded stents and, therefore, exhibited larger displacement. Stents with an open-cell design, such as Express-like or Xience-like stents, had a higher bending flexibility. Stents …

Cardiac Surgery: A Century Of Progress, Allen B Weisse

The Texas Heart Institute Journal

Well into the first decades of the 20th century, medical opinion held that any surgical attempts to treat heart disease were not only misguided, but unethical. Despite such reservations, innovative surgeons showed that heart wounds could be successfully repaired. Then, extracardiac procedures were performed to correct patent ductus arteriosus, coarctation of the aorta, and tetralogy of Fallot. Direct surgery on the heart was accomplished with closed commissurotomy for mitral stenosis. The introduction of the heart-lung machine and cardiopulmonary bypass enabled the surgical treatment of other congenital and acquired heart diseases. Advances in aortic surgery paralleled these successes. The development of …

Measuring The Symptom Burden Of Lung Cancer: The Validity And Utility Of The Lung Cancer Module Of The M D Anderson Symptom Inventory, Tito R Mendoza, Xin Shelley Wang, Charles Lu, Guadalupe R Palos, Zhongxing Liao, Gary M Mobley, Shitij Kapoor, Charles S Cleeland

Faculty, Staff and Student Publications

We conducted a study to establish the psychometric properties of a module of the M. D. Anderson Symptom Inventory (MDASI) developed specifically for patients with lung cancer (MDASI-LC). The MDASI measures 13 common "core" symptoms of cancer and its treatment. The MDASI-LC includes the 13 core MDASI symptom items and three lung cancer-specific items: coughing, constipation, and sore throat. MDASI-LC items were administered to three cohorts of patients with lung cancer undergoing either chemotherapy or chemoradiotherapy. Known-group validity and criterion (concurrent) validity of the MDASI-LC were evaluated using the Eastern Cooperative Oncology Group performance status and the 12-item Short-Form Health …

Probing The Mechanical Properties Of Tnf-A Stimulated Endothelial Cell With Atomic Force Microscopy, Sei-Young Lee, Ana-Maria Zaske, Tommaso Novellino, Delia Danila, Mauro Ferrari, Jodie Conyers, Paolo Decuzzi

Faculty, Staff and Student Publications

TNF-α (tumor necrosis factor-α) is a potent pro-inflammatory cytokine that regulates the permeability of blood and lymphatic vessels. The plasma concentration of TNF-α is elevated (> 1 pg/mL) in several pathologies, including rheumatoid arthritis, atherosclerosis, cancer, pre-eclampsia; in obese individuals; and in trauma patients. To test whether circulating TNF-α could induce similar alterations in different districts along the vascular system, three endothelial cell lines, namely HUVEC, HPMEC, and HCAEC, were characterized in terms of 1) mechanical properties, employing atomic force microscopy; 2) cytoskeletal organization, through fluorescence microscopy; and 3) membrane overexpression of adhesion molecules, employing ELISA and immunostaining. Upon stimulation …

Complete Genome Sequence Of Treponema Paraluiscuniculi, Strain Cuniculi A: The Loss Of Infectivity To Humans Is Associated With Genome Decay, David Smajs, Marie Zobaníková, Michal Strouhal, Darina Cejková, Shannon Dugan-Rocha, Petra Pospíšilová, Steven J Norris, Tom Albert, Xiang Qin, Kym Hallsworth-Pepin, Christian Buhay, Donna M Muzny, Lei Chen, Richard A Gibbs, George M Weinstock

Faculty, Staff and Student Publications

Treponema paraluiscuniculi is the causative agent of rabbit venereal spirochetosis. It is not infectious to humans, although its genome structure is very closely related to other pathogenic Treponema species including Treponema pallidum subspecies pallidum, the etiological agent of syphilis. In this study, the genome sequence of Treponema paraluiscuniculi, strain Cuniculi A, was determined by a combination of several high-throughput sequencing strategies. Whereas the overall size (1,133,390 bp), arrangement, and gene content of the Cuniculi A genome closely resembled those of the T. pallidum genome, the T. paraluiscuniculi genome contained a markedly higher number of pseudogenes and gene fragments (51). In …

Alterations In Content And Localization Of Defensins In Rat Ileum And Jejunum Following Ischemia-Reperfusion Specific Peptides, In Specific Places, For Specific Jobs?, Rosemary A Kozar, Rachel J Santora, Brian J Poindexter, Stephen M Milner, Roger J Bick

Faculty, Staff and Student Publications

Objective: To determine alterations in quantities and distributions of natural antimicrobials following ischemia-reperfusion injury. We hypothesized that these compounds would be upregulated in areas of small intestine where changes in permeability and cellular disruption were likely and where protective mechanisms would be initiated. Methods: Rats with ischemia-reperfusion underwent superior mesenteric artery clamping and reperfusion. Shams were subjected to laparotomy but no clamping. Ileum and jejunum were harvested and sectioned, and subjected to fluorescence deconvolution microscopy for determinations of content and localization of rat beta defensins, 1, 2, 3; rat neutrophil protein-1; and cathelicidin LL-37. Modeling was performed to determine cellular …

Association Of Retinoic Acid Receptor Genes With Meningomyelocele, Phong X Tran, Kit Sing Au, Alanna C Morrison, Jack M Fletcher, Kathryn K Ostermaier, Gayle H Tyerman, Hope Northrup

Faculty, Staff and Student Publications

BACKGROUND: Neural tube defects (NTDs) occur in as many as 0.5-2 per 1000 live births in the United States. One of the most common and severe neural tube defects is meningomyelocele (MM) resulting from failed closure of the caudal end of the neural tube. MM has been induced by retinoic acid teratogenicity in rodent models. We hypothesized that genetic variants influencing retinoic acid (RA) induction via retinoic acid receptors (RARs) may be associated with risk for MM.

METHODS: We analyzed 47 single nucleotide polymorphisms (SNPs) that span across the three retinoic acid receptor genes using the SNPlex genotyping platform. Our …

Immunopathology Of Postprimary Tuberculosis: Increased T-Regulatory Cells And Dec-205-Positive Foamy Macrophages In Cavitary Lesions, Kerry J Welsh, Semyon A Risin, Jeffrey K Actor, Robert L Hunter

Faculty, Staff and Student Publications

Postprimary tuberculosis occurs in immunocompetent people infected with Mycobacterium tuberculosis. It is restricted to the lung and accounts for 80% of cases and nearly 100% of transmission. Little is known about the immunopathology of postprimary tuberculosis due to limited availability of specimens. Tissues from 30 autopsy cases of pulmonary tuberculosis were located. Sections of characteristic lesions of caseating granulomas, lipid pneumonia, and cavitary stages of postprimary disease were selected for immunohistochemical studies of macrophages, lymphocytes, endothelial cells, and mycobacterial antigens. A higher percentage of cells in lipid pneumonia (36.1%) and cavitary lesions (27.8%) were positive for the dendritic cell marker …

Stat!Ref Medical News Feed;Top 25 Electronic Journals, Vol.8 (12),, Houston Academy Of Medicine-Texas Medical Center Library

Insider Express (2003-2013)

No abstract provided.

Characterizing And Treating The Neuropathology Of Tuberous Sclerosis Complex In The Mouse, Sharon W. Way

Dissertations and Theses (Open Access)

Tuberous sclerosis complex (TSC) is a multisystem, autosomal dominant disorder affecting approximately 1 in 6000 births. Developmental brain abnormalities cause substantial morbidity and mortality and often lead to neurological disease including epilepsy, cognitive disabilities, and autism. TSC is caused by inactivating mutations in either TSC1 or TSC2, whose protein products are known inhibitors of mTORC1, an important kinase regulating translation and cell growth. Nonetheless, neither the pathophysiology of the neurological manifestations of TSC nor the extent of mTORC1 involvement in the development of these lesions is known. Murine models would greatly advance the study of this debilitating disorder. This thesis …

Rmi1 Is Essential For Early Embryonic Development And Attenuation Of Tumor Development, Haoyi Chen

Dissertations and Theses (Open Access)

RMI1 (BLM-Associated Protein 75 or Blap75) is highly conserved from yeast to human. Previous studies have shown that hRMI1 is required for BLM/TopoIIIα/RMI1 complex stability and function. However, in vivo functions of RMI1 remain elusive. To address this question, I generated RMI1 knockout mice by homologous replacement targeting. While RMI1+/- mice showed no obvious phenotype, deletion of both RMI1 alleles leads to early embryonic lethality before implantation. I then generated RMI1/p53 double knockout mice. After ionizing radiation treatment at 4Gy, RMI1/p53 double-heterzygous mice showed shortened tumor latency and aggressive tumor types when comparing with wild type, RMI1+/- and p53+/- control …

New To Ols For Monitoring Gamma Camera Uniformity, Brad K. Lofton

Dissertations and Theses (Open Access)

Detector uniformity is a fundamental performance characteristic of all modern gamma camera systems, and ensuring a stable, uniform detector response is critical for maintaining clinical images that are free of artifact. For these reasons, the assessment of detector uniformity is one of the most common activities associated with a successful clinical quality assurance program in gamma camera imaging. The evaluation of this parameter, however, is often unclear because it is highly dependent upon acquisition conditions, reviewer expertise, and the application of somewhat arbitrary limits that do not characterize the spatial location of the non-uniformities. Furthermore, as the goal of any …

Analysis Of Β8 Integrin In Neurogenesis And Neurovascular Homeostasis, Aaron K. Mobley

Dissertations and Theses (Open Access)

Neurogenesis in the adult mouse brain occurs within the subventricular zone (SVZ) of the lateral ventricle. In the SVZ, neural stem cells (NSC) reside in a specialized microenvironment, or vascular niche, consisting of blood vessels and their basement membranes. Most NSCs in the SVZ differentiate into progenitor cells, which further differentiate to generate neuroblasts, which then migrate from the SVZ to the olfactory bulbs (OB) along the rostral migratory stream (RMS). ECM-mediated adhesion and signaling within the vascular niche likely contribute to proper NSC self-renewal, survival, differentiation and neuroblast motility. The mechanisms that control these events are poorly understood. Previous …

Elucidating Functional Roles For Myogenin In Adult Skeletal Muscle Metabolism, Exercise Capacity, And Regeneration, Jesse Flynn

Dissertations and Theses (Open Access)

The four basic helix-loop-helix myogenic transcription factors, myogenin, Myf5, MRF4, and MyoD are critical for embryonic skeletal muscle development. Myogenin is necessary for the terminal differentiation of myoblasts into myofibers during embryogenesis, but little is known about the roles played by myogenin in adult skeletal muscle function and metabolism. Furthermore, while metabolism is a well-studied physiological process, how it is regulated at the transcriptional level remains poorly understood. In this study, my aim was to determine the function of myogenin in adult skeletal muscle metabolism, exercise capacity, and regeneration. To investigate this, I utilized a mouse strain harboring the Myogflox …

The Immune Inhibitor A1 Protease Of Bacillus Anthracis, Kathryn Pflughoeft

Dissertations and Theses (Open Access)

Bacillus anthracis, an organism ubiquitous in the soil and the causative agent of anthrax, utilizes multiple mechanisms to regulate secreted factors; one example is the activity of secreted proteases. One of the most abundant proteins in the culture supernates of B. anthracis is the Immune Inhibitor A1 (InhA1) protease. Here, I demonstrate that InhA1 modulates the abundance of approximately half of the proteins secreted into the culture supernates, including substrates that are known to contribute to the ability of the organism to cause virulence. For example, InhA1 cleaves the anthrax toxin proteins, PA, LF, and EF. InhA1 also targets …

Stress-Induced Targeting Of Molecular Chaperones In The Yeast Saccharomyces Cerevisiae, Hugo Tapia

Dissertations and Theses (Open Access)

The eukaryotic stress response is an essential mechanism that helps protect cells from a variety of environmental stresses. Cell death can result if cells are not able to properly adapt and protect themselves against adverse stress conditions. Failure to properly deal with stress has implications in human diseases including neurodegenerative disorders and distinct cancers, emphasizing the importance of understanding the eukaryotic stress response in detail. As part of this response, expression of a battery of heat shock proteins (HSP) is induced, which act as molecular chaperones to assist in the repair or triage of unfolded proteins. The 90-kDa HSP (Hsp90) …

Plasmacytoid Dendritic Cells Sense Skin Injury And Promote Wound Healing Through Type I Interferons, Josh D. Gregorio

Dissertations and Theses (Open Access)

Plasmacytoid dendritic cells (pDCs) are a rare population of circulating cells, which selectively express intracellular Toll-like receptors (TLR)-7 and TLR-9 and have the capacity to produce large amounts of type I IFNs (IFN-a/b) in response to viruses or host derived nucleic acid containing complexes. pDCs are normally absent in skin but accumulate in the skin of psoriasis patients where their chronic activation to produce IFN-a/b drives the disease formation. Whether pDCs and their activation to produce IFN-a/b play a functional role in healthy skin is unknown. Here we show that pDCs are rapidly and transiently recruited into healthy human and …

The Role Of Post-Translation Regulation Of Twist Expression In The Tumor Progression Of Squamous Cell Carcinoma Of Head And Neck, Ying-Wen Su

Dissertations and Theses (Open Access)

Squamous cell carcinoma of head and neck (SCCHN) is the tenth most common cancer in the world. Unfortunately, the survival of patients with SCCHN has not improved in the last 40 years. Therefore new targets for therapy are needed, and to this end we are studying signaling pathways activated by IL-6 which we have found stimulates cell migration and soft agar growth in SCCHN. Our data show that IL-6 increases TWIST expression in a transcription-independent mechanism in many SCCHN cell lines. Further investigation reveals TWIST can be phosphorylated upon IL-6 treatment. By computation prediction (http://scansite.mit.edu/motifscan_seq.phtml ), we found that TWIST …

Network To Pology In Human Protein Interaction Data Predicts Functional Association, Hua Li

Dissertations and Theses (Open Access)

High-throughput assays, such as yeast two-hybrid system, have generated a huge amount of protein-protein interaction (PPI) data in the past decade. This tremendously increases the need for developing reliable methods to systematically and automatically suggest protein functions and relationships between them. With the available PPI data, it is now possible to study the functions and relationships in the context of a large-scale network. To data, several network-based schemes have been provided to effectively annotate protein functions on a large scale. However, due to those inherent noises in high-throughput data generation, new methods and algorithms should be developed to increase the …

Agrobacterium Virb10 Contributions To Type Iv Substrate Secretion, T-Pilus Biogenesis, And Outer Membrane Pore Formation, Isaac Garza

Dissertations and Theses (Open Access)

The VirB/D4 type IV secretion system (T4SS) of Agrobacterium tumefaciens functions to transfer substrates to infected plant cells through assembly of a translocation channel and a surface structure termed a T-pilus. This thesis is focused on identifying contributions of VirB10 to substrate transfer and T-pilus formation through a mutational analysis. VirB10 is a bitopic protein with several domains, including a: (i) cytoplasmic N-terminus, (ii) single transmembrane (TM) α-helix, (iii) proline-rich region (PRR), and (iv) large C-terminal modified β-barrel. I introduced cysteine insertion and substitution mutations throughout the length of VirB10 in order to: (i) test a predicted transmembrane topology, (ii) …

Analyzing The Role Of Αvβ8 Integrin In Glioma-Induced Angiogenesis, Jeremy H. Tchaicha

Dissertations and Theses (Open Access)

In this study we aimed to determine the functional roles for αvβ8 integrin in astrocytoma-induced angiogenesis. These studies originate from our analyses of αvβ8 integrin in developmental brain angiogenesis. αv and β8 knockout (KO) mice develop brain-specific vascular phenotypes that resemble vascular pathologies observed in the malignant astrocytoma, glioblastoma multiforme (GBM). Indeed, a murine xenograft model of astrocytoma suggested a role for the integrin in glioma-induced angiogenesis. Primary mouse astroglia were cultured from wild type (WT) and β8 KO neonates and were immortalized (HPV:E6/E7) and transformed (HRas:G12V). WT and β8 KO transformed astroglia were intracranially injected into athymic mice. WT …