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Temozolomide And Bevacizumab Therapy In Advanced Hemangiopericytoma/ Solitary Fibrous Tumor, Min S. Park

Dissertations & Theses (Open Access)

Tumors comprising the spectrum of hemangiopericytoma/ malignant solitary fibrous tumor (HPC/SFT) are thought to arise from fibroblasts and represent a small subset of soft tissue sarcomas. Surgery is typically the treatment of choice for localized disease, with reported 10-year overall survival rates of 54-89% after complete surgical resection. However, for the approximately 20% of HPC/SFT patients who eventually develop local recurrences and/or distant metastases, options for effective treatment are limited and are poorly defined. Alternative therapeutic options are therefore needed for improved palliation and disease control. We hypothesize that HPC/SFT are a spectrum of soft tissue tumors with unique clinical, …

Characterization Of Optically Stimulated Luminescent Detectors In Photon & Proton Beams For Use In Anthropomorphic Phantoms, James R. Kerns

Dissertations & Theses (Open Access)

This study investigated characteristics of optically stimulated luminescent detectors (OSLDs) in protons, allowing comparison to thermoluminescent detectors, and to be implemented into the Radiological Physics Center’s (RPC) remote audit quality assurance program for protons, and for remote anthropomorphic phantom irradiations. The OSLDs used were aluminum oxide (Al2O3:C) nanoDots from Landauer, Inc. (Glenwood, Ill.) measuring 10x10x2 mm3. A square, 20(L)x20(W)x0.5(H) cm3 piece of solid water was fabricated with pockets to allow OSLDs and TLDs to be irradiated simultaneously and perpendicular to the beam. Irradiations were performed at 5cm depth in photons, and in the center of a 10 cm SOBP in …

An Innovative Phase I Trial Design Allowing For The Identification Of Multiple Potential Maximum Tolerated Doses With Combination Therapy Of Targeted Agents, Sarina A. Piha-Paul

Dissertations & Theses (Open Access)

Treatment for cancer often involves combination therapies used both in medical practice and clinical trials. Korn and Simon listed three reasons for the utility of combinations: 1) biochemical synergism, 2) differential susceptibility of tumor cells to different agents, and 3) higher achievable dose intensity by exploiting non-overlapping toxicities to the host. Even if the toxicity profile of each agent of a given combination is known, the toxicity profile of the agents used in combination must be established. Thus, caution is required when designing and evaluating trials with combination therapies. Traditional clinical design is based on the consideration of a single …

An Implantable Mosfet Dosimeter Modified To Act As A Fiducial Marker, Joseph S. Dick

Dissertations & Theses (Open Access)

In external beam radiation therapy, it is imperative that the prescribed dose is administered to the correct location and in the correct amount. Though several ex vivo methods of quality assurance are currently employed to achieve this goal, verifying that the correct dose is received within the patient in situ is impossible without the capability of measuring dose inside the patient. Recently, a method of measuring dose delivered within the patient has been developed, an implantable MOSFET dosimeter. This dosimeter is implanted within the patient and records the dose received. Since the dosimeter is implanted in the patient, it could …

Benchmarking And Implementation Of A New Independent Monte Carlo Dose Calculation Quality Assurance Audit Tool For Clinical Trials, Scott E. Davidson

Dissertations & Theses (Open Access)

Introduction Commercial treatment planning systems employ a variety of dose calculation algorithms to plan and predict the dose distributions a patient receives during external beam radiation therapy. Traditionally, the Radiological Physics Center has relied on measurements to assure that institutions participating in the National Cancer Institute sponsored clinical trials administer radiation in doses that are clinically comparable to those of other participating institutions. To complement the effort of the RPC, an independent dose calculation tool needs to be developed that will enable a generic method to determine patient dose distributions in three dimensions and to perform retrospective analysis of radiation …

Dynamic Chemical Shift Imaging For Image-Guided Thermal Therapy, Brian A. Taylor

Dissertations & Theses (Open Access)

Magnetic resonance temperature imaging (MRTI) is recognized as a noninvasive means to provide temperature imaging for guidance in thermal therapies. The most common method of estimating temperature changes in the body using MR is by measuring the water proton resonant frequency (PRF) shift. Calculation of the complex phase difference (CPD) is the method of choice for measuring the PRF indirectly since it facilitates temperature mapping with high spatiotemporal resolution. Chemical shift imaging (CSI) techniques can provide the PRF directly with high sensitivity to temperature changes while minimizing artifacts commonly seen in CPD techniques. However, CSI techniques are currently limited by …

Effect Of Acute Administration Of Angiopoietin-1 In Experimental Traumatic Spinal Cord Injury: Magnetic Resonance Imaging And Neurobehavioral Studies, Chirag B. Patel

Dissertations & Theses (Open Access)

Spinal cord injury (SCI) is a devastating condition that affects people in the prime of their lives. A myriad of vascular events occur after SCI, each of which contributes to the evolving pathology. The primary trauma causes mechanical damage to blood vessels, resulting in hemorrhage. The blood-spinal cord barrier (BSCB), a neurovascular unit that limits passage of most agents from systemic circulation to the central nervous system, breaks down, resulting in inflammation, scar formation, and other sequelae. Protracted BSCB disruption may exacerbate cellular injury and hinder neurobehavioral recovery in SCI.

In these studies, angiopoietin-1 (Ang1), an agent known to reduce …

Histamine Reduces Flash Sensitivity Of On Ganglion Cells In The Primate Retina, Nikolay P Akimov, David W Marshak, Laura J Frishman, Randolph D Glickman, Rafail G Yusupov

Journal Articles

PURPOSE. In Old World primates, the retina receives input from histaminergic neurons in the posterior hypothalamus. They are a subset of the neurons that project throughout the central nervous system and fire maximally during the day. The contribution of these neurons to vision, was examined by applying histamine to a dark-adapted, superfused baboon eye cup preparation while making extracellular recordings from peripheral retinal ganglion cells. METHODS. The stimuli were 5-ms, 560-nm, weak, full-field flashes in the low scotopic range. Ganglion cells with sustained and transient ON responses and two cell types with OFF responses were distinguished; their responses were recorded …

Progressive Regression Of Left Ventricular Hypertrophy Two Years After Bariatric Surgery, Mohamed F Algahim, Thomas R Lux, Joshua G Leichman, Anthony F Boyer, Charles C Miller, Susan T Laing, Erik B Wilson, Terry Scarborough, Sherman Yu, Brad Snyder, Carol Wolin-Riklin, Ursula G Kyle, Heinrich Taegtmeyer

Journal Articles

BACKGROUND: Obesity is a systemic disorder associated with an increase in left ventricular mass and premature death and disability from cardiovascular disease. Although bariatric surgery reverses many of the hormonal and hemodynamic derangements, the long-term collective effects on body composition and left ventricular mass have not been considered before. We hypothesized that the decrease in fat mass and lean mass after weight loss surgery is associated with a decrease in left ventricular mass.

METHODS: Fifteen severely obese women (mean body mass index [BMI]: 46.7+/-1.7 kg/m(2)) with medically controlled hypertension underwent bariatric surgery. Left ventricular mass and plasma markers of systemic …

A Direct Role For Secretory Phospholipase A2 And Lysophosphatidylcholine In The Mediation Of Lps-Induced Gastric Injury, Elizabeth J Dial, Duy M Tran, Jimmy J Romero, Mayssa Zayat, Lenard M Lichtenberger

Journal Articles

Endotoxemia from sepsis can injure the gastrointestinal tract through mechanisms that have not been fully elucidated. We have shown that LPS induces an increase in gastric permeability in parallel with the luminal appearance of secretory phospholipase A2 (sPLA2) and its product, lysophosphatidylcholine (lyso-PC). We proposed that sPLA2 acted on the gastric hydrophobic barrier, composed primarily of phosphatidylcholine (PC), to degrade it and produce lyso-PC, an agent that is damaging to the mucosa. In the present study, we have tested whether lyso-PC and/or sPLA2 have direct damaging effects on the hydrophobic barriers of synthetic and mucosal surfaces. Rats were administered LPS …

Cellular Dynamic Simulator: An Event Driven Molecular Simulation Environment For Cellular Physiology, Michael J Byrne, M Neal Waxham, Yoshihisa Kubota

Journal Articles

In this paper, we present the Cellular Dynamic Simulator (CDS) for simulating diffusion and chemical reactions within crowded molecular environments. CDS is based on a novel event driven algorithm specifically designed for precise calculation of the timing of collisions, reactions and other events for each individual molecule in the environment. Generic mesh based compartments allow the creation / importation of very simple or detailed cellular structures that exist in a 3D environment. Multiple levels of compartments and static obstacles can be used to create a dense environment to mimic cellular boundaries and the intracellular space. The CDS algorithm takes into …

Thoracic Aortic Disease In Tuberous Sclerosis Complex: Molecular Pathogenesis And Potential Therapies In Tsc2+/- Mice, Jiumei Cao, Limin Gong, Dong-Chuan Guo, Ulrike Mietzsch, Shao-Qing Kuang, Callie S Kwartler, Hazim Safi, Anthony Estrera, Michael J Gambello, Dianna M Milewicz

Journal Articles

Tuberous sclerosis complex (TSC) is a genetic disorder with pleiotropic manifestations caused by heterozygous mutations in either TSC1 or TSC2. One of the less investigated complications of TSC is the formation of aneurysms of the descending aorta, which are characterized on pathologic examination by smooth muscle cell (SMC) proliferation in the aortic media. SMCs were explanted from Tsc2(+/-) mice to investigate the pathogenesis of aortic aneurysms caused by TSC2 mutations. Tsc2(+/-) SMCs demonstrated increased phosphorylation of mammalian target of rapamycin (mTOR), S6 and p70S6K and increased proliferation rates compared with wild-type (WT) SMCs. Tsc2(+/-) SMCs also had reduced expression of …

Osteopontin And Cadherin 11 Are Novel Mediators And Drug Targets For Chronic Lung Diseases, Daniel J. Schneider

Dissertations & Theses (Open Access)

Chronic lung diseases (CLDs) are a considerable source of morbidity and mortality and are thought to arise from dysregulation of normal wound healing processes. An aggressive, feature of many CLDs is pulmonary fibrosis (PF) and is characterized by excess deposition of extracellular matrix (ECM) proteins from myofibroblasts in airways. However, factors regulating myofibroblast biology are incompletely understood. Proteins in the cadherin family contribute epithelial to mesenchymal transition (EMT), a suggested source of myofibroblasts. Cadherin 11 (CDH11) contributes to developmental and pathologic processes that parallel those seen in PF and EMT. Utilizing Cdh11 knockout (Cdh11 -/-) mice, the goal of this …

A New Tumor Suppressor Gene Candidate Regulated By The Non-Coding Rna Pca3 In Human Prostate Cancer, Alessandro K. Lee

Dissertations & Theses (Open Access)

Prostate cancer is the second leading cause of cancer-related death and the most common non-skin cancer in men in the USA. Considerable advancements in the practice of medicine have allowed a significant improvement in the diagnosis and treatment of this disease and, in recent years, both incidence and mortality rates have been slightly declining. However, it is still estimated that 1 man in 6 will be diagnosed with prostate cancer during his lifetime, and 1 man in 35 will die of the disease.

In order to identify novel strategies and effective therapeutic approaches in the fight against prostate cancer, it …

Il-2 Regulation Of Il-24 Expression Leads To Growth Suppression Of Melanoma Cells, Emily Jen

Dissertations & Theses (Open Access)

Melanoma is known to be highly resistant to chemotherapy. Treatment with high dose IL-2 has shown significant clinical benefit in a minority of metastatic melanoma patients and has lead to long term survival in a few cases. However, this treatment is associated with excessive multiorgan toxicities, which severely limits its use. We hypothesize that one mechanism of effective IL-2 therapy is through the direct upregulation of IL-24 production in melanoma tumors and subsequent IL-24 mediated tumor growth suppression.

Five melanoma cell lines were treated with high dose recombinant hIL-2 at 1000U/ml. Three of the cell lines (A375, WM1341, WM793) showed …

Perfusion In Rat Brain At 7 T With Arterial Spin Labeling Using Fair-Truefisp And Quipss, Emilio Esparza-Coss, Jarek Wosik, Ponnada A Narayana

Journal Articles

Measurement of perfusion in longitudinal studies allows for the assessment of tissue integrity and the detection of subtle pathologies. In this work, the feasibility of measuring brain perfusion in rats with high spatial resolution using arterial spin labeling is reported. A flow-sensitive alternating recovery sequence, coupled with a balanced gradient fast imaging with steady-state precession readout section was used to minimize ghosting and geometric distortions, while achieving high signal-to-noise ratio. The quantitative imaging of perfusion using a single subtraction method was implemented to address the effects of variable transit delays between the labeling of spins and their arrival at the …

Thoracic Radiotherapy Treatment Planning With Cine Pet/Ct, Adam C. Riegel

Dissertations & Theses (Open Access)

Purpose: Respiratory motion causes substantial uncertainty in radiotherapy treatment planning. Four-dimensional computed tomography (4D-CT) is a useful tool to image tumor motion during normal respiration. Treatment margins can be reduced by targeting the motion path of the tumor. The expense and complexity of 4D-CT, however, may be cost-prohibitive at some facilities. We developed an image processing technique to produce images from cine CT that contain significant motion information without 4D-CT. The purpose of this work was to compare cine CT and 4D-CT for the purposes of target delineation and dose calculation, and to explore the role of PET in target …

First Trimester Screening And Its Impact On Uptake Of Diagnostic Testing, Deanna Darnes

Dissertations & Theses (Open Access)

Introduction: First Trimester Screening (FTS) combines maternal age with fetal nuchal translucency (NT) and maternal analytes to identify pregnancies at an increased risk for Down syndrome and trisomy 18. Though the accuracy of this screening is high, it cannot replace the conclusive accuracy of prenatal diagnostic testing (PDT). Since FTS has been available, a decrease in the number of women who pursue PDT has been observed. This study sought to determine if there has been a significant change in the amount of PDT performed in our clinics, if the type of FTS result affects the patient’s decision regarding PDT, and …

A Randomized Trial Of Bilevel Positive Airway Pressure Device And High Flow Oxygen For Persistent Dyspnea In, David Hui

Dissertations & Theses (Open Access)

Background: Dyspnea is a common and distressing symptom among patients with advanced cancer. The role of bilevel positive airway pressure (BIPAP) and Vapotherm in the relief of dyspnea have not been well defined. We aimed to determine and to compare the efficacy of BIPAP and VapoTherm for cancer related dyspnea.

Methods: In this randomized, open-label, crossover study, we randomly assigned advanced cancer patients with persistent dyspnea >=3/10 to either Vapotherm for 2 hours followed by BiPAP for 2 hours, or BiPAP followed by Vaptherm. A variable washout period was instituted between interventions. The primary end point was change in numeric …

Syntaxin 3b Is Essential For The Exocytosis Of Synaptic Vesicles In Ribbon Synapses Of The Retina, L Curtis, P Datta, X Liu, N Bogdanova, R Heidelberger, R Janz

Journal Articles

Ribbon synapses of the vertebrate retina are specialized synapses that release neurotransmitter by synaptic vesicle exocytosis in a manner that is proportional to the level of depolarization of the cell. This release property is different from conventional neurons, in which the release of neurotransmitter occurs as a short-lived burst triggered by an action potential. Synaptic vesicle exocytosis is a calcium regulated process that is dependent on a set of interacting synaptic proteins that form the so-called SNARE (soluble N-ethylmaleimide sensitive factor attachment protein receptor) complex. Syntaxin 3B has been identified as a specialized SNARE molecule in ribbon synapses of the …

Three-Dimensional Structure Of Tropism-Switching Bordetella Bacteriophage, Wei Dai, Asher Hodes, Wong H Hui, Mari Gingery, Jeff F Miller, Z Hong Zhou

Journal Articles

Bacteriophage BPP-1, which infects Bordetella species, can switch its specificity by mutations to the ligand-binding surface of its major tropism-determinant protein, Mtd. This targeted mutagenesis results from the activity of a phage-encoded diversity-generating retroelement. Purified Mtd binds its receptor with low affinity, yet BPP-1 binding and infection of Bordettella cells are efficient because of high-avidity binding between phage-associated Mtd and its receptor. Here, using an integrative approach of three-dimensional (3D) structural analyses of the entire phage by cryo-electron tomography and single-prticle cryo-electron microscopy, we provide direct localization of Mtd in the phage and the structural basis of the high-avidity binding …

Maternal And Neonatal Outcomes By Labor Onset Type And Gestational Age, Jennifer L Bailit, Kimberly D Gregory, Uma M Reddy, Victor H Gonzalez-Quintero, Judith U Hibbard, Mildred M Ramirez, D Ware Branch, Ronald Burkman, Shoshana Haberman, Christos G Hatjis, Matthew K Hoffman, Michelle Kominiarek, Helain J Landy, Lee A Learman, James Troendle, Paul Van Veldhuisen, Isabelle Wilkins, Liping Sun, Jun Zhang

Journal Articles

OBJECTIVE: We sought to determine maternal and neonatal outcomes by labor onset type and gestational age.

STUDY DESIGN: We used electronic medical records data from 10 US institutions in the Consortium on Safe Labor on 115,528 deliveries from 2002 through 2008. Deliveries were divided by labor onset type (spontaneous, elective induction, indicated induction, unlabored cesarean). Neonatal and maternal outcomes were calculated by labor onset type and gestational age.

RESULTS: Neonatal intensive care unit admissions and sepsis improved with each week of gestational age until 39 weeks (P < .001). After adjusting for complications, elective induction of labor was associated with a lower risk of ventilator use (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.28-0.53), sepsis (OR, 0.36; 95% CI, 0.26-0.49), and neonatal intensive care unit admissions (OR, 0.52; 95% CI, 0.48-0.57) compared to spontaneous labor. The relative risk of hysterectomy at term was 3.21 (95% CI, 1.08-9.54) with elective induction, 1.16 (95% CI, 0.24-5.58) with indicated induction, and 6.57 (95% CI, 1.78-24.30) with cesarean without labor compared to spontaneous labor.

CONCLUSION: Some neonatal outcomes improved until 39 weeks. Babies born with elective induction …

Cardiomyocyte Pdgfr-Beta Signaling Is An Essential Component Of The Mouse Cardiac Response To Load-Induced Stress, Vishnu Chintalgattu, Di Ai, Robert R Langley, Jianhu Zhang, James A Bankson, Tiffany L Shih, Anilkumar K Reddy, Kevin R Coombes, Iyad N Daher, Shibani Pati, Shalin S Patel, Jennifer S Pocius, George E Taffet, L Maximillian Buja, Mark L Entman, Aarif Y Khakoo

Journal Articles

PDGFR is an important target for novel anticancer therapeutics because it is overexpressed in a wide variety of malignancies. Recently, however, several anticancer drugs that inhibit PDGFR signaling have been associated with clinical heart failure. Understanding this effect of PDGFR inhibitors has been difficult because the role of PDGFR signaling in the heart remains largely unexplored. As described herein, we have found that PDGFR-beta expression and activation increase dramatically in the hearts of mice exposed to load-induced cardiac stress. In mice in which Pdgfrb was knocked out in the heart in development or in adulthood, exposure to load-induced stress resulted …

Temporal Lobe White Matter Asymmetry And Language Laterality In Epilepsy Patients, Timothy M Ellmore, Michael S Beauchamp, Joshua I Breier, Jeremy D Slater, Giridhar P Kalamangalam, Thomas J O'Neill, Michael A Disano, Nitin Tandon

Journal Articles

Recent studies using diffusion tensor imaging (DTI) have advanced our knowledge of the organization of white matter subserving language function. It remains unclear, however, how DTI may be used to predict accurately a key feature of language organization: its asymmetric representation in one cerebral hemisphere. In this study of epilepsy patients with unambiguous lateralization on Wada testing (19 left and 4 right lateralized subjects; no bilateral subjects), the predictive value of DTI for classifying the dominant hemisphere for language was assessed relative to the existing standard-the intra-carotid Amytal (Wada) procedure. Our specific hypothesis is that language laterality in both unilateral …

Elevated Albumin In Retinas Of Monkeys With Experimental Glaucoma, Louvenia Carter-Dawson, Yujin Zhang, Ronald S Harwerth, Ricky Rojas, Pramod Dash, Xinping C Zhao, Elizabeth Woldemussie, Guadalupe Ruiz, Alice Chuang, William P Dubinsky, John B Redell

Journal Articles

PURPOSE: To establish the identity of a prominent protein, approximately 70 kDa, that is markedly increased in the retina of monkeys with experimental glaucoma compared with the fellow control retina, the relationship to glaucoma severity, and its localization in the retina.

METHODS: Retinal extracts were subjected to 2-D gel electrophoresis to identify differentially expressed proteins. Purified peptides from the abundant 70 kDa protein were analyzed and identified by liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) separation, and collision-induced dissociation sequencing. Protein identity was performed on MASCOT (Matrix Science, Boston, MA) and confirmed by Western blot. The relationship between the increase in this …

Humoral Immunity In Tuberculin Skin Test Anergy And Its Role In High-Risk Persons Exposed To Active Tuberculosis, Liliana Encinales, Joaquin Zuñiga, Julio Granados-Montiel, Maria Yunis, Julio Granados, Ingrid Almeciga, Olga Clavijo, Carlos Awad, Vilma Collazos, María Inés Vargas-Rojas, José Luis Bañales-Mendez, Lilia Vazquez-Castañeda, Joel N Stern, Viviana Romero, Masha Fridkis-Hareli, Masha Frindkis-Hareli, Daniel Terreros, Marcelo Fernandez-Viña, Edmond J Yunis

Journal Articles

The most common test to identify latent tuberculosis is the tuberculin skin test that detects T cell responses of delayed type hypersensitivity type IV. Since it produces false negative reactions in active tuberculosis or in high-risk persons exposed to tuberculosis patients as shown in this report, we studied antibody profiles to explain the anergy of such responses in high-risk individuals without active infection. Our results showed that humoral immunity against tuberculin, regardless of the result of the tuberculin skin test is important for protection from active tuberculosis and that the presence of high antibody titers is a more reliable indicator …

A Woman With Hiv Infection, Brain Abscesses, And Eosinophilia, Marcela Campo, Man K Phung, Rehan Ahmed, Paul Cantey, Henry Bishop, Tanvir K Bell, Carolyn Gardiner, Cesar A Arias

Journal Articles

No abstract provided.

Study Of Polytopic Membrane Protein Topological Organization As A Function Of Membrane Lipid Composition, Mikhail Bogdanov, Philip N Heacock, William Dowhan

Journal Articles

A protocol is described using lipid mutants and thiol-specific chemical reagents to study lipid-dependent and host-specific membrane protein topogenesis by the substituted-cysteine accessibility method as applied to transmembrane domains (SCAM). SCAM is adapted to follow changes in membrane protein topology as a function of changes in membrane lipid composition. The strategy described can be adapted to any membrane system.

Social Support In An Internet Weight Loss Community, Kevin O Hwang, Allison J Ottenbacher, Angela P Green, M Roseann Cannon-Diehl, Oneka Richardson, Elmer V Bernstam, Eric J Thomas

Journal Articles

PURPOSE: To describe social support for weight loss shared by members of a large Internet weight loss community.

METHODS: We conducted a mixed-methods study with surveys (n=193) and interviews (n=13) of community members along with a content analysis of discussion forum messages (n=1924 messages). Qualitative data were analyzed for social support themes.

RESULTS: Survey respondents were primarily white (91.4%) and female (93.8%) with mean age 37.3 years and mean body mass index 30.9. They used forums frequently, with 56.8% reading messages, 36.1% replying to messages, and 18.5% posting messages to start a discussion related to weight loss on a daily …

Safety, Tolerability, And Efficacy Of Fixed Combination Therapy With Dorzolamide Hydrochloride 2% And Timolol Maleate 05% In Glaucoma And Ocular Hypertension, Nicholas P Bell, José L Ramos, Robert M Feldman

Journal Articles

Glaucoma is a collection of diseases characterized by multifactorial progressive changes leading to visual field loss and optic neuropathy most frequently due to elevated intraocular pressure (IOP). The goal of treatment is the lowering of the IOP to prevent additional optic nerve damage. Treatment usually begins with topical pharmacological agents as monotherapy, progresses to combination therapy with agents from up to 4 different classes of IOP-lowering medications, and then proceeds to laser or incisional surgical modalities for refractory cases. The fixed combination therapy with the carbonic anhydrase inhibitor dorzolamide hydrochloride 2% and the beta blocker timolol maleate 0.5% is now …