Medicine and Health Sciences Commons^™

Characterization Of Hsp70 Binding And Nucleotide Exchange By The Yeast Hsp110 Chaperone Sse1, Lance Shaner, Rui Sousa, Kevin A Morano

Journal Articles

SSE1 and SSE2 encode the essential yeast members of the Hsp70-related Hsp110 molecular chaperone family. Both mammalian Hsp110 and the Sse proteins functionally interact with cognate cytosolic Hsp70s as nucleotide exchange factors. We demonstrate here that Sse1 forms high-affinity (Kd approximately 10-8 M) heterodimeric complexes with both yeast Ssa and mammalian Hsp70 chaperones and that binding of ATP to Sse1 is required for binding to Hsp70s. Sse1.Hsp70 heterodimerization confers resistance to exogenously added protease, indicative of conformational changes in Sse1 resulting in a more compact structure. The nucleotide binding domains of both Sse1/2 and the Hsp70s dictate interaction specificity and …

Acute And Chronic Methylphenidate Dose-Response Assessment On Three Adolescent Male Rat Strains, Pamela B Yang, Alan C Swann, Nachum Dafny

Journal Articles

Methylphenidate (MPD), commonly known as Ritalin, is the most frequently prescribed drug to treat children and adults with attention deficit hyperactivity disorder (ADHD). Adolescence is a period of development involving numerous neuroplasticities throughout the central nervous system (CNS). Exposure to a psychostimulant such as MPD during this crucial period of neurodevelopment may cause transient or permanent changes in the CNS. Genetic variability may also influence these differences. Thus, the objective of the present study was to determine whether acute and chronic administration of MPD (0.6, 2.5, or 10.0mg/kg, i.p.) elicit effects among adolescent WKY, SHR, and SD rats and to …

Glycosylation Regulates Turnover Of Cyclooxygenase-2., Mary B. Sevigny, Chai-Fei Li, Monika Alas, Millie Hughes-Fulford

Natural Sciences and Mathematics | Faculty Scholarship

Cyclooxygenase-2 (COX-2) catalyzes the rate-limiting step in the prostanoid biosynthesis pathway, converting arachidonic acid into prostaglandin H(2). COX-2 exists as 72 and 74kDa glycoforms, the latter resulting from an additional oligosaccharide chain at residue Asn(580). In this study, Asn(580) was mutated to determine the biological significance of this variable glycosylation. COS-1 cells transfected with the mutant gene were unable to express the 74kDa glycoform and were found to accumulate more COX-2 protein and have five times greater COX-2 activity than cells expressing both glycoforms. Thus, COX-2 turnover appears to depend upon glycosylation of the 72kDa glycoform.

Atomoxetine Treatment In Children And Adolescents With Attention-Deficit Hyperactivity Disorder: What Are The Long-Term Health-Related Quality-Of-Life Outcomes?, Amy R. Perwien, Christopher J. Kratochvil, Douglas E. Faries, Brigette S. Vaughan, Thomas Spencer, Ronald T. Brown

Journal Articles: Psychiatry

OBJECTIVE: Numerous investigations have examined the efficacy of pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD) in children. However, relatively few studies have addressed the impact of treatment on long-term subjective, psychosocial outcomes, such as health-related quality of life (HRQL). This study examines the long-term effects of pharmacological treatment with atomoxetine on HRQL in children and adolescents with ADHD.

METHODS: Participants included 6- to 17-year-old children and adolescents (n = 912) with ADHD enrolled in a 24-month, multicenter, open-label trial of atomoxetine. Outcomes included clinician ratings of ADHD, parent ratings of ADHD, and a widely used measure of HRQL (The Child Health …

Treatment For Adolescents With Depression Study (Tads): Safety Results., Graham Emslie, Christopher J. Kratochvil, Benedetto Vitiello, Susan Silva, Taryn Mayes, Steven Mcnulty, Elizabeth Weller, Bruce Waslick, Charles Casat, John Walkup, Sanjeev Pathak, Paul Rohde, Kelly Posner, John March, The Columbia Suicidality Classification Group, Tads Team

Journal Articles: Psychiatry

OBJECTIVE: To compare the rates of physical, psychiatric, and suicide-related events in adolescents with MDD treated with fluoxetine alone (FLX), cognitive-behavioral therapy (CBT), combination treatment (COMB), or placebo (PBO).

METHOD: Safety assessments included adverse events (AEs) collected by spontaneous report, as well as systematic measures for specific physical and psychiatric symptoms. Suicidal ideation and suicidal behavior were systematically assessed by self- and clinician reports. Suicidal events were also reanalyzed by the Columbia Group and expert raters using the Columbia-Classification Algorithm for Suicidal Assessment used in the U.S. Food and Drug Administration reclassification effort.

RESULTS: Depressed adolescents reported high rates of …

Androgen-Regulated Formation And Degradation Of Gap Junctions In Androgen-Responsive Human Prostate Cancer Cells., Shalini Mitra, Lakshmanan Annamalai, Souvik Chakraborty, Kristen E. Johnson, Xiao-Hong Song, Surinder K. Batra, Parmender P. Mehta

Journal Articles: Biochemistry & Molecular Biology

The constituent proteins of gap junctions, called connexins (Cxs), have a short half-life. Despite this, the physiological stimuli that control the assembly of Cxs into gap junctions and their degradation have remained poorly understood. We show here that in androgen-responsive human prostate cancer cells, androgens control the expression level of Cx32-and hence the extent of gap junction formation-post-translationally. In the absence of androgens, a major fraction of Cx32 is degraded presumably by endoplasmic reticulum-associated degradation, whereas in their presence, this fraction is rescued from degradation. We also show that Cx32 and Cx43 degrade by a similar mechanism. Thus, androgens regulate …

Guidelines And Standards For Performance Of A Pediatric Echocardiogram: A Report From The Task Force Of The Pediatric Council Of The American Society Of Echocardiography., Wyman W. Lai, Tal Geva, Girish S. Shirali, Peter C. Frommelt, Richard A. Humes, Michael M. Brook, Ricardo H. Pignatelli, Jack Rychik, Pediatric Council Of The American Society Of Echocardiography

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Bovine Immune Response To Shiga-Toxigenic Escherichia Coli O157:H7., Mark A Hoffman, Christian Menge, Thomas A Casey, William Laegreid, Brad T Bosworth, Evelyn A Dean-Nystrom

Manuscripts, Articles, Book Chapters and Other Papers

Although cattle develop humoral immune responses to Shiga-toxigenic (Stx+) Escherichia coli O157:H7, infections often result in long-term shedding of these human pathogenic bacteria. The objective of this study was to compare humoral and cellular immune responses to Stx+ and Stx- E. coli O157:H7. Three groups of calves were inoculated intrarumenally, twice in a 3-week interval, with different strains of E. coli: a Stx2-producing E. coli O157:H7 strain (Stx2+ O157), a Shiga toxin-negative E. coli O157:H7 strain (Stx- O157), or a nonpathogenic E. coli strain (control). Fecal shedding of Stx2+ O157 was significantly higher than that of Stx- O157 or the …

Nucleolin Is Required For Rna Polymerase I Transcription In Vivo, Brendan Rickards, S. Flint, Michael D. Cole, Gary Leroy

Dartmouth Scholarship

Eukaryotic genomes are packaged with histones and accessory proteins in the form of chromatin. RNA polymerases and their accessory proteins are sufficient for transcription of naked DNA, but not of chromatin, templates in vitro. In this study, we purified and identified nucleolin as a protein that allows RNA polymerase II to transcribe nucleosomal templates in vitro. As immunofluorescence confirmed that nucleolin localizes primarily to nucleoli with RNA polymerase I, we demonstrated that nucleolin allows RNA polymerase I transcription of chromatin templates in vitro. The results of chromatin immunoprecipitation experiments established that nucleolin is associated with chromatin containing rRNA genes transcribed …

Insights Into Transcription Enhancer Factor 1 (Tef-1) Activity From The Solution Structure Of The Tea Domain, Asokan Anbanandam, Diana C Albarado, Catherine T Nguyen, Georg Halder, Xiaolian Gao, Sudha Veeraraghavan

Journal Articles

Transcription enhancer factor 1 is essential for cardiac, skeletal, and smooth muscle development and uses its N-terminal TEA domain (TEAD) to bind M-CAT elements. Here, we present the first structure of TEAD and show that it is a three-helix bundle with a homeodomain fold. Structural data reveal how TEAD binds DNA. Using structure-function correlations, we find that the L1 loop is essential for cooperative loading of TEAD molecules on to tandemly duplicated M-CAT sites. Furthermore, using a microarray chip-based assay, we establish that known binding sites of the full-length protein are only a subset of DNA elements recognized by TEAD. …

Cdx4 Dysregulates Hox Gene Expression And Generates Acute Myeloid Leukemia Alone And In Cooperation With Meis1a In A Murine Model, Dimple Bansal, Claudia Scholl, Stefan Frohling, Elizabeth Mcdowell, Benjamin H. Lee, Konstanze Döhner, Patricia Ernst

Dartmouth Scholarship

HOX genes have emerged as critical effectors of leukemogenesis, but the mechanisms that regulate their expression in leukemia are not well understood. Recent data suggest that the caudal homeobox transcription factors CDX1, CDX2, and CDX4, developmental regulators of HOX gene expression, may contribute to HOX gene dysregulation in leukemia. We report here that CDX4 is expressed normally in early hematopoietic progenitors and is expressed aberrantly in approximately 25% of acute myeloid leukemia (AML) patient samples. Cdx4 regulates Hox gene expression in the adult murine hematopoietic system and dysregulates Hox genes that are implicated in leukemogenesis. Furthermore, bone marrow progenitors that …

Treatment Of Solid Organ Transplant Recipients With Autologous Epstein Barr Virus-Specific Cytotoxic T Lymphocytes (Ctls)., Barbara Savoldo, John A. Goss, Markus M. Hammer, Lan Zhang, Teresita Lopez, Adrian P. Gee, Yu-Feng Lin, Ruben E. Quiros-Tejeira, Petra Reinke, Stephan Schubert, Stephen Gottschalk, Milton J. Finegold, Malcolm K. Brenner, Cliona M. Rooney, Helen E. Heslop

Faculty Publications

We have investigated the in vivo safety, efficacy, and persistence of autologous Epstein Barr virus (EBV)-specific cytotoxic T lymphocytes (CTLs) for the treatment of solid organ transplant (SOT) recipients at high risk for EBV-associated posttransplantation lymphoproliferative disease (PTLD). EBV-CTLs generated from 35 patients expanded with normal kinetics contained both CD8 and CD4 lymphocytes and produced significant specific killing of autologous EBV-transformed B lymphoblastoid cell lines (LCLs). Twelve SOT recipients at high risk for PTLD, or with active disease, received autologous CTL infusions without toxicity. Real-time polymerase chain reaction (PCR) monitoring of EBV-DNA showed a transient increase in plasma EBV-DNA suggestive …

Dermatology Is A Specialty; Dermatology Is Not A Subspecialty., Lawrence Parish, Larry E Millikan

Department of Dermatology and Cutaneous Biology Faculty Papers

Specialization began in American medicine about the time of the War Between the States. Several factors spurred the direction of practitioners away from being the so-called “complete physicians. Most important were the advances in instrumentation made by the 1860’s, which allowed ophthalmology and otolaryngology to develop into distinct divisions of allopathic medicine; sometimes, they even joined together, viz eye, ear, nose, and throat specialist. Dermatology, too, became one of the early specialties for a myriad of reasons ranging from the obvious – visual inspection - to the mundane, viz. default – syphilis was too ugly and complicated for every physician …

Patient Education In Glaucoma: What Do Patients Know About Glaucoma?, Vital Paulino Costa, George L Spaeth, Maura Smith, Cordelia Uddoh, José Paulo Cabral Vasconcellos, Newton Kara-José

Wills Eye Hospital Papers

PURPOSE: To evaluate the knowledge glaucoma patients have about their disease and its treatment.

METHODS: One hundred and eighty-three patients were interviewed at the Glaucoma Service of Wills Eye Hospital (Philadelphia, USA, Group 1) and 100 at the Glaucoma Service of University of Campinas (Campinas, Brazil, Group 2). An informal, relaxed atmosphere was created by the interviewer before asking a list of 18 open-ended questions.

RESULTS: In Group 1, 44% of the 183 patients did not have an acceptable idea about what glaucoma is, 30% did not know the purpose of the medications they were taking, 47% were not aware …

The Effect Of Timing Of Radiotherapy After Breast-Conserving Surgery In Patients With Positive Or Close Resection Margins, Young Age, And Node-Negative Disease, With Long Term Follow-Up, Olga Vujovic, Anil Cherian, Edward Yu, A. Dar, Larry Stitt, Francisco Perera

Edward Yu

Purpose: The aim of this study was to determine the effect of timing of radiotherapy after conservative breast surgery on local recurrence in women with positive resection margins and young age, treated without systemic therapy. Methods and materials: A total of 568 patients with T1 and T2, N0 breast cancer were treated with breast-conserving surgery and breast irradiation, between January 1, 1985, and December 31, 1992, at the London Regional Cancer Centre. 63 patients (11.1%) had positive/close resection margins (< 2 mm) and 48 patients (8.4%) were age < or = 40 years. For patients with positive resection margins, the time intervals from breast surgery to breast irradiation used for analysis were, 0 to 8 weeks, > 8 to 12 weeks and > 12 weeks. For patients < or = 40 years, the intervals used for analysis were 0 to 8 weeks and > 8 weeks. Results: Median follow up was 11.2 years. For patients …

Navigating Adolescence With A Chronic Health Condition: A Perspective On The Psychological Effects Of Hair-An Syndrome On Adolescent Girls, Kimberly K. Mcclanahan, Hatim A. Omar

Pediatrics Faculty Publications

HAIR-AN syndrome is a subphenotype of polycystic ovary syndrome and is characterized by acne, obesity, hirsutism, and acanthosis nigricans. It usually manifests in early adolescence, a time of significant developmental change in females across physical, cognitive, social, and emotional domains. We contend that adolescent development for females is difficult, even in the best of circumstances, and having a chronic health condition, like HAIR-AN syndrome, will likely impact the afflicted individual's development and psychological well-being. While many researchers have discussed the long-term health effects of HAIR-AN and similar disorders, little has been written about the potential psychological sequelae of HAIR-AN on …

Effects Of A Personified Guide On Adherence To An Online Program For Alcohol Abusers., Daniel Z Lieberman

Psychiatry and Behavioral Sciences Faculty Publications

The quality of the therapeutic alliance has robust effects on the outcome of psychotherapy and psychopharmacologic interventions. Automated behavioral health programs that are being developed to increase access to mental health treatment are administered in the absence of direct human participation, thereby precluding the development of a traditional therapeutic relationship. The aim of this study was to develop a personified guide designed to stimulate reactions similar to those experienced in a therapeutic relationship, and evaluate the effect of the guide on adherence to and satisfaction with an online alcohol use evaluation program. After completing a battery of four standard questionnaires …

Treatment Evolution In High-Risk Congenital Diaphragmatic Hernia: Ten Years' Experience With Diaphragmatic Agenesis, Kevin P Lally, Pamela A Lally, Krisa P Van Meurs, Desmond J Bohn, Carl F Davis, Bradley Rodgers, Jatinder Bhatia, Golde Dudell

Journal Articles

OBJECTIVE: The objective of this study was to evaluate the impact of newer therapies on the highest risk patients with congenital diaphragmatic hernia (CDH), those with agenesis of the diaphragm.

SUMMARY BACKGROUND DATA: CDH remains a significant cause of neonatal mortality. Many novel therapeutic interventions have been used in these infants. Those children with large defects or agenesis of the diaphragm have the highest mortality and morbidity.

METHODS: Twenty centers from 5 countries collected data prospectively on all liveborn infants with CDH over a 10-year period. The treatment and outcomes in these patients were examined. Patients were followed until death …

Time To Renal Disease And End-Stage Renal Disease In Profile: A Multiethnic Lupus Cohort, Graciela S. Alarcón, Gerald Mcgwin, Michelle Petri, Rosalind Ramsey-Goldman, Barri J. Fessler, Luis M. Vilá, Jeffrey C. Edberg, John D. Reveille, Robert P. Kimberly

Journal Articles

BACKGROUND: Renal involvement is a serious manifestation of systemic lupus erythematosus (SLE); it may portend a poor prognosis as it may lead to end-stage renal disease (ESRD). The purpose of this study was to determine the factors predicting the development of renal involvement and its progression to ESRD in a multi-ethnic SLE cohort (PROFILE).

METHODS AND FINDINGS: PROFILE includes SLE patients from five different United States institutions. We examined at baseline the socioeconomic-demographic, clinical, and genetic variables associated with the development of renal involvement and its progression to ESRD by univariable and multivariable Cox proportional hazards regression analyses. Analyses of …

Platelet-Activating Factor Is Crucial In Psoralen And Ultraviolet A-Induced Immune Suppression, Inflammation, And Apoptosis., Peter Wolf, Dat X Nghiem, Jeffrey P Walterscheid, Scott Byrne, Yumi Matsumura, Yasuhiro Matsumura, Cora Bucana, Honnavara N Ananthaswamy, Stephen E Ullrich

Journal Articles

Psoralen plus UVA (PUVA) is used as a very effective treatment modality for various diseases, including psoriasis and cutaneous T-cell lymphoma. PUVA-induced immune suppression and/or apoptosis are thought to be responsible for the therapeutic action. However, the molecular mechanisms by which PUVA acts are not well understood. We have previously identified platelet-activating factor (PAF), a potent phospholipid mediator, as a crucial substance triggering ultraviolet B radiation-induced immune suppression. In this study, we used PAF receptor knockout mice, a selective PAF receptor antagonist, a COX-2 inhibitor (presumably blocking downstream effects of PAF), and PAF-like molecules to test the role of PAF …

Open Versus Laparoscopic Pyloromyotomy For Pyloric Stenosis: A Prospective, Randomized Trial., Shawn D. St Peter, G W. Holcomb Iii, Casey M. Calkins, J Patrick Murphy, Walter S. Andrews, Ronald J. Sharp, Charles L. Snyder, Daniel J. Ostlie

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Pyloric stenosis, the most common surgical condition of infants, is treated by longitudinal myotomy of the pylorus. Comparative studies to date between open and laparoscopic pyloromyotomy have been retrospective and report conflicting results. To scientifically compare the 2 techniques, we conducted the first large prospective, randomized trial between the 2 approaches.

METHODS: After obtaining IRB approval, subjects with ultrasound-proven pyloric stenosis were randomized to either open or laparoscopic pyloromyotomy. Postoperative pain management, feeding schedule, and discharge criteria were identical for both groups. Operating time, postoperative emesis, analgesia requirements, time to full feeding, length of hospitalization after operation, and complications …

Minimizing Radiation Injury And Neoplastic Effects During Pediatric Fluoroscopy: What Should We Know?, Louis Kenneth Wagner

Journal Articles

Radiation-induced injuries from fluoroscopic procedures in pediatric patients have occurred, and young patients are at greatest risk of many radiation-induced neoplasms. Some fluoroscopists have been injured from their use of fluoroscopy, and they are known to be at risk of radiation-induced neoplasm when radiation is not well-controlled. This article reviews the circumstances that lead to radiation injury and delineates some procedural methods to avoid injury and limit radiation exposure to both the patient and the fluoroscopist.

From Healing The Whole Person: An Argument For Therapeutic Touch As A Complement To Traditional Medical Practice, Marlene B. Huff, Kimberly K. Mcclanahan, Hatim A. Omar

Pediatrics Faculty Publications

The growing popularity and use of therapeutic touch (TT) is an issue that has generated controversy and concern within the medical community. While anecdotal and traditional scientific evidence suggest that TT would be an advantageous addition for clinics and hospitals to include in their armamentarium of complementary interventions within the realm of traditional medicine, TT has not become widely available in the U.S. One reason for the lack of availability may be the dearth of conclusive scientific support for TT's efficacy and, therefore, its inclusion in clinic and hospital treatment planning would give it the appearance of legitimate practice, which …

Pregnant Teenager Involvement In Sexual Activity And The Social Context, Maria José Carvalho Sant'anna, Júlia Kerr Catunda, Kepler Alencar Mendes Carvalho, Verônica Coates, Hatim A. Omar

Pediatrics Faculty Publications

Pregnancy during adolescence represents a challenge to society as a whole. Its incidence is increasing and brings about social and medical consequences to both the teen mothers and their children. The purpose of this study was to evaluate pregnant teenager involvement in sexual activity and the social context. The group studied comprised 152 pregnant teenagers attending the Department of Pediatrics, Santa Casa de Sao Paulo (SCSP) General Hospital. All information was analyzed. The age at first intercourse was 14.2 years and the average period between first intercourse and pregnancy was 1.4 years. Most pregnancies (75%) were neither planned nor wanted, …

Cyclin D1 Repression Of Nuclear Respiratory Factor 1 Integrates Nuclear Dna Synthesis And Mitochondrial Function., Chenguang Wang, Zhiping Li, Yinan Lu, Runlei Du, Sanjay Katiyar, Jianguo Yang, Maofu Fu, Jennifer E Leader, Andrew Quong, Phyllis M Novikoff, Richard Pestell

Department of Cancer Biology Faculty Papers

Cyclin D1 promotes nuclear DNA synthesis through phosphorylation and inactivation of the pRb tumor suppressor. Herein, cyclin D1 deficiency increased mitochondrial size and activity that was rescued by cyclin D1 in a Cdk-dependent manner. Nuclear respiratory factor 1 (NRF-1), which induces nuclear-encoded mitochondrial genes, was repressed in expression and activity by cyclin D1. Cyclin D1-dependent kinase phosphorylates NRF-1 at S47. Cyclin D1 abundance thus coordinates nuclear DNA synthesis and mitochondrial function.

Arsenic Exposure Is Associated With Decreased Dna Repair In Vitro And In Individuals Exposed To Drinking Water Arsenic, Angeline S. Andrew, Jefferey L. Burgess, Maria M. Meza, Eugene Demidenko, Mary G. Waugh, Joshua W. Hamilton, Margaret R. Karagas

Dartmouth Scholarship

The mechanism(s) by which arsenic exposure contributes to human cancer risk is unknown; however, several indirect cocarcinogenesis mechanisms have been proposed. Many studies support the role of As in altering one or more DNA repair processes. In the present study we used individual-level exposure data and biologic samples to investigate the effects of As exposure on nucleotide excision repair in two study populations, focusing on the excision repair cross-complement 1 (ERCC1) component. We measured drinking water, urinary, or toenail As levels and obtained cryopreserved lymphocytes of a subset of individuals enrolled in epidemiologic studies in New Hampshire (USA) and Sonora …

Cell-Cycle Regulatory Proteins In The Podocyte In Collapsing Glomerulopathy In Children., Tarak Srivastava, Robert E. Garola, H K. Singh

Manuscripts, Articles, Book Chapters and Other Papers

Podocyte is a terminally committed cell in G1 arrest of cell cycle, and is unable to overcome G1/S transition phase in children with minimal change disease (MCD) and classic focal segmental glomerulosclerosis (FSGS), in contrast to dysregulated proliferative phenotype of idiopathic collapsing glomerulopathy (CGN) in adults. Forty-two kidney biopsies, MCD (14), FSGS (12), CGN (4), and normal (CON) (12), were evaluated by immunohistochemistry using dual staining for expression of p27, p21, and p57, and cyclins D and A, in podocytes of children with CGN. On light microscopy, all podocytes expressed p27, whereas p21 and p57 expression was seen in a …

Syndrome Of Inappropriate Antidiuretic Hormone Secretion (Siadh) In Patients With Limited Stage Small Cell Lung Cancer, Patricia Tai, Edward Yu, Kurian Jones, Evgeny Sadikov, Shazia Mahmood, Jon Tonita

Edward Yu

A few series in the literature were published before 1987 on syndrome of inappropriate antidiuretic hormone secretion (SIADH) in small cell lung cancer (SCLC). This study examines the outcome in more recent era. From 1981-1998, there were 1417 new cases of SCLC diagnosed in the provincial registry, of which 244 were of limited stage (LS). A chart review and statistical analyses were performed using Mann-Whitney test, chi-square test and Kaplan-Meier method. Fourteen LS patients (group A) had SIADH at presentation. Group B consisted of 230 LS patients without SIADH. There were more patients with poorer performance status (ECOG 2-4) in …

Natriuretic Peptides And Nitric Oxide Stimulate Cgmp Synthesis In Different Cellular Compartments., Leslie A Piggott, Kathryn A Hassell, Zuzana Berkova, Andrew P Morris, Michael Silberbach, Thomas C Rich

Journal Articles

Cyclic nucleotide-gated (CNG) channels are a family of ion channels activated by the binding of cyclic nucleotides. Endogenous channels have been used to measure cyclic nucleotide signals in photoreceptor outer segments and olfactory cilia for decades. Here we have investigated the subcellular localization of cGMP signals by monitoring CNG channel activity in response to agonists that activate either particulate or soluble guanylyl cyclase. CNG channels were heterologously expressed in either human embryonic kidney (HEK)-293 cells that stably overexpress a particulate guanylyl cyclase (HEK-NPRA cells), or cultured vascular smooth muscle cells (VSMCs). Atrial natriuretic peptide (ANP) was used to activate the …

The Role Of Radiation Therapy In Malignant Pleural Mesothelioma: A Systematic Review, Yee Ung, Edward Yu, Conrad Falkson, Adam Haynes, Denise Stys-Norman, William Evans

Edward Yu

Introduction: Radiation therapy may offer patients presenting with malignant pleural mesothelioma (MPM) symptom palliation and improvements in quality of life. This systematic review will address the role of radiation therapy in the management of MPM. Methods: A thorough systematic search of the literature was conducted for published articles and conference proceedings for applicable abstracts. Relevant trials were selected and assessed. Results: Three small randomized controlled trials compared prophylactic external beam radiation therapy to no radiation therapy for patients with thoracic tracts caused by drainage tubes or diagnostic procedures. None of those trials reported any serious adverse effects. A pooled analysis …