tbuckley/cabot-search huggingface dataset:
Abstract LB-220: TMEM16A, a novel calcium-activated chloride channel, modulates tumor proliferation via MAPK and Cyclin-D1 signaling
Authors: Daniel Shiwarski, Carol Bertrand, Ann Marie Egloff, Xin Huang, Raja Seethala, Jennifer Grandis, Susanne Gollin, Umamaheswar Duvvuri
Journal: Cancer Research (2011)

Abstract TMEM16A, a calcium-activated chloride channel, was recently isolated from oral cavity cancer cells. TMEM16A is amplified in head and neck cancers and overexpressed in gastrointestinal stromal tumors (GIST's); however, the role that TMEM16A plays in promoting tumor growth remains unclear. The goal of this research was to establish the biologic function of TMEM16A in the context of epithelial malignancies. We hypothesized that TMEM16A contributes to tumor cell survival and may be a useful prognostic factor for patients with squamous cell carcinoma of the head and neck (SCCHN). Knockdown and overexpressing SCCHN and T24 cell lines were transduced with lentiviral particles encoding RNAi and engineered to stably overexpress TMEM16A. For functional verification, electrophysiologic assays were performed to establish that the altered TMEM16A expression was modulating the chloride current. To elucidate a mechanism of TMEM16A's proliferative effects, immunoblotting and pharmacologic inhibition of potential downstream targets were performed. Our results demonstrate that the levels of TMEM16A expression modulates proliferation in vitro and in vivo, and that stable overexpression of TMEM16A increases resistance to cisplatin therapy as compared to cancer cell lines expressing endogenous TMEM16A. Specificity of these phenotypic results were confirmed using genetic rescue experiments. Next, we identified that the MAPK/Cyclin-D1 axis was a critical signaling pathway in TMEM16A-induced proliferation, and that pMAPK/MAPK and Cyclin-D1 levels paralleled expression of TMEM16A. Finally, using pharmacologic agents niflumic acid or NPPB to inhibit the TMEM16A chloride channel activity in combination with a MAPK inhibitor (U0126) demonstrated additive effects significantly decreasing cancer cell proliferation in vitro. In summary, our results provide novel insights into the biologic function of TMEM16A and its role in tumor cell proliferation. This research has enhanced our understanding about the pathogenesis of SCCHN tumors, and can potentially be translated to many other cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-220. doi:10.1158/1538-7445.AM2011-LB-220
An Unusual Cause of Multiple Splenic Infarcts
Authors: MICHAEL G. VELCHIK, JOHN HANSELL, P TODD MAKLER, ABASS ALAVI
Journal: Clinical Nuclear Medicine (1983)

VELCHIK, MICHAEL G. M.D.; HANSELL, JOHN M.D.; MAKLER, P TODD Jr. M.D.; ALAVI, ABASS M.D. Author Information
Reviews, Notes, and Listings: Nephrology: Diagnostic Techniques in Renal Disease
Authors: Gregory L. Braden
Journal: Annals of Internal Medicine (1993)

Literature of Medicine15 August 1993Reviews, Notes, and Listings: Nephrology: Diagnostic Techniques in Renal DiseaseGregory L. BradenGregory L. BradenBaystate Medical Center, Springfield, MA 01199.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-119-4-199308150-00044 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Diagnostic Techniques in Renal DiseaseRobert G. Narins; ed. 384 pages. New York: Churchill Livingstone; 1992. $82.00.Despite major advances in the diagnosis of renal diseases in the last 20 years, the diagnosis of acid-base disorders, electrolyte disorders and renal diseases is still difficult, often resting on the exclusion of all other possibilities after the entire differential diagnosis has been considered. To date, no renal textbook has focused on the diagnostic dilemmas that face the practicing nephrologist. Narins is the first editor to attempt to fill this void. His book is designed to enlighten readers with fresh insight into diagnosing ... Author, Article, and Disclosure InformationAffiliations: Baystate Medical Center, Springfield, MA 01199. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 August 1993Volume 119, Issue 4Page: 352KeywordsBiopsyDiagnostic techniquesPotassiumRadiologistsRed blood cellsRenal diseasesRenal failureRenal transplantationTransplant rejection ePublished: 15 August 2000 Issue Published: 15 August 1993 Copyright & PermissionsCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Immunologically relevant peptide antigen exists on the presenting cell in a manner accessible to macromolecules in solution.
Authors: K B Cease, G Buckenmeyer, I Berkower, J York-Jolley, J A Berzofsky
Journal: The Journal of Experimental Medicine (1986)

Although studies of the association of antigen with APC have been complicated by antigen-processing requirements, recent studies have suggested that immunologically relevant antigen should be present on the APC surface. Nevertheless, blocking of antigen presentation with antibody to the antigen has not been demonstrable in most systems. To study this problem we developed a system using avidin to block presentation of amino-terminal biotinylated synthetic peptide 132-146 of sperm whale myoglobin (B132) to a murine T cell clone specific for this site in association with I-Ed. greater than 95% specific inhibition was observed with doses of B132 equipotent to unmodified peptide. Specific blocking could be observed: (a) after pulsing APC with antigen, washing, and incubating for a chase period of 8-16 h before addition of avidin and T cells to assure adequate time for intracellular trafficking and maximal display of antigen on the cell surface, or (b) when monensin is present during the antigen pulse to inhibit such traffic. Therefore, the inhibition appeared to be occurring at the cell surface unless dissociation and reassociation were constantly occurring. To distinguish these, B10.GD APC (I-Ed-negative) were pulsed with antigen and cocultured with B10.D2 APC (I-Ed-positive). No detectable antigen presentation resulted. Thus, minimal dissociation and reassociation between antigen and APC occurs and, consequently, blocking by extracellular solution-phase binding of avidin to antigen is unlikely. Taken together, these data suggest that the blocking is occurring at the cell surface. Thus, under physiologic conditions, immunologically relevant antigen necessary for T cell activation appears to be present on the APC surface and is freely accessible to macromolecules the size of avidin. These findings hold specific implications for models of antigen presentation for T cell recognition.
Hypofractionated Radiotherapy for Breast Cancer
Authors: Joanne S Haviland, John R Yarnold, Søren M Bentzen
Journal: New England Journal of Medicine (2010)

Cross-study comparisons are limited.There are important differences between the U.K. and Canadian trials that could account for the discrepancy in findings (e.g., a shorter follow-up, inclusion of node-positive patients, and the use of boost radiation and anthracyclines). 1-3Furthermore, our analysis on tumor grade was post hoc and only one of five factors that we considered.The differential effect between treatments in patients with high-grade tumors requires validation through future research.Meanwhile, we believe it is premature to make any decisions concerning the avoidance of hypofractionated radiation in treating women with high-grade tumors.
Presidential Disability and the Twenty-fifth Amendment
Authors: Steven Miles
Journal: JAMA (1995)

<h3>To the Editor.</h3> —The disclosure of President Reagan's Alzheimer's disease shows the difficulty of early identification and forthright discussion of potential presidential disability from slowly progressive neurologic diseases. Reagan's physicians announced that annual examinations had included "thorough memory testing." They colloquially said that he "is entering the early stages of this disease," ambiguously omitting standardized staging. One physician wrote, "It was only in the past 12 months—six years out of the White House—that his physicians saw clinical signs and results of tests that lead to a diagnosis of Alzheimer's disease. In no way did this disease predate the past year."<sup>1</sup>Physician-patient confidentiality is cited to support this vagueness. Such reticence differs from reports of Reagan's other illnesses.<sup>2,3</sup>Synopses of the management of a gunshot wound, subdural hematoma, and colon cancer give diagnostic tests, normal baseline data needed to establish trends, standard staging, and an account of medical reasoning.
Rehabilitation after head injury--1: Cognitive problems.
Authors: D Gloag
Journal: BMJ (1985)

In the course of my travels I saw two young people at two stages of their lengthy rehabilitation after severe head injury in road accidents. At a regional neurological unit a boy of 18 was taking his first steps nine months after his injury; I met him nine months later at a day rehabilitation centre, walking well and talking much more easily. The girl, also about 18, I first saw 11 months after her accident, barely conscious, in the rehabilitation department of a large residential home. Two years later she was still there, and I watched her in the physiotherapy room practising single steps and single sounds with great concentration; she was said to have guts and her family hoped to have her home one day. But intensive, speciahst rehabilitation is available to few, and at some centres that do provide it courses may be too short.1 The problem is sizable. Head injuries treated in hospital number 250 a year per 100 000 population, with a prevalence of 150 survivors with major disability per 100000.2 According to another estimate, each year 210 people are left totally disabled and a further 1500  disabled3; while it was estimated in 1967 that some 1000 people a year were left as lamebrains with permanent psycho? logical impairment.4 Less than a fifth of survivors of severe head injury would be classified as severely disabled, mentally or physic? ally, six months later.5 But they are mainly young, with years of disability ahead of them. Some survivors moreover pose enormous problems of long term care (2 February, p 369); I saw one man unnecessarily in a teaching hospital seven years after his accident, because his wife would not have him and nowhere else would either.
Trends in mortality from tuberculosis in England and Wales: effect of age on deaths from non-respiratory disease.
Authors: M J Doherty, D P Spence, P D Davies
Journal: Thorax (1995)

BACKGROUND--Although mortality from tuberculosis has continued to fall in recent years, there has been little change in the case fatality rate for tuberculosis over the same period. This has previously been shown to be due to the increasing proportion of cases of tuberculosis occurring in the elderly. Tuberculosis mortality and case fatality were therefore analysed to determine if this disappointing trend in case fatality rate has occurred from disease in all or only certain sites. METHODS--A retrospective analysis of the tuberculosis mortality and case fatality rates in England and Wales for the period 1972-92 was carried out. The average annual percentage change in tuberculosis was calculated for each disease site and by age group and the results were compared. RESULTS--The analysis showed that, although the mortality rate fell steadily by 5.6% per annum, the case fatality rate decreased by only 0.9% (95% CI -1.7 to -0.1) per annum. The case fatality rate for respiratory and central nervous system disease declined, but no decline in tuberculosis at "other" sites was observed (1.01% (+2.2 to -0.2) for all age groups combined). In the group aged 75 and over, however, the proportion of deaths due to disease at other sites increased by 3.2% (2.2 to 4.3) per annum whilst in the other age groups the mortality rate declined. CONCLUSIONS--This analysis suggests that clinicians may be becoming less able to recognise non-respiratory presentations of tuberculosis, particularly in the elderly, and underlines the need to consider tuberculosis as a diagnosis to avoid delay in treatment.
Chorioamnionitis and Cerebral Palsy in Term and Near-Term Infants
Authors: Yvonne W. Wu
Journal: JAMA (2003)

ContextHalf of all cases of cerebral palsy (CP) occur in term infants, for whom risk factors have not been clearly defined. Recent studies suggest a possible role of chorioamnionitis.ObjectiveTo determine whether clinical chorioamnionitis increases the risk of CP in term and near-term infants.Design, Setting, and PatientsCase-control study nested within a cohort of 231 582 singleton infants born at 36 or more weeks' gestation between January 1, 1991, and December 31, 1998, in the Kaiser Permanente Medical Care Program, a managed care organization providing care for more than 3 million residents of northern California. Case patients were identified from electronic records and confirmed by chart review by a child neurologist, and comprised all children with moderate to severe spastic or dyskinetic CP not due to postnatal brain injury or developmental abnormalities (n = 109). Controls (n = 218) were randomly selected from the study population.Main Outcome MeasureAssociation between clinical chorioamnionitis and increased risk of CP in term and near-term infants.ResultsMost CP cases had hemiparesis (40%) or quadriparesis (38%); 87% had been diagnosed by a neurologist and 83% had undergone neuroimaging. Chorioamnionitis, considered present if a treating physician made a diagnosis of chorioamnionitis or endometritis clinically, was noted in 14% of cases and 4% of controls (odds ratio [OR], 3.8; 95% confidence interval [CI], 1.5-10.1; P = .001). Independent risk factors identified in multiple logistic regression included chorioamnionitis (OR, 4.1; 95% CI, 1.6-10.1), intrauterine growth restriction (OR, 4.0; 95% CI, 1.3-12.0), maternal black ethnicity (OR, 3.6; 95% CI, 1.4-9.3), maternal age older than 25 years (OR, 2.6; 95% CI, 1.3-5.2), and nulliparity (OR, 1.8; 95% CI, 1.0-3.0). The population-attributable fraction of chorioamnionitis for CP is 11%.ConclusionOur data suggest that chorioamnionitis is an independent risk factor for CP among term and near-term infants.
TCT-418 Doppler Control Of Radial Artery After Use of TR Band Following Coronarography and/or Angioplasty : DRABAND study results
Authors: Jacques Monsegu, Martial Hamon, Jose Fernandez Diaz, Rachid Briki, Monica Masotti, Mariano Valdes, Yves Louvard, David Hildick-Smith
Journal: Journal of the American College of Cardiology (2012)
INCREASE OF URIC ACID IN THE BLOOD DURING PROLONGED STARVATION
Authors: WILLIAM G. LENNOX
Journal: JAMA (1924)

In the course of studies dealing with the chemistry of the blood of epileptic patients during starvation treatment, a marked increase in the concentration of the uric acid in the blood has been found. Observations have been made during twenty-two starvation periods, varying in length from three to twenty-one days, on nineteen subjects. Two of these were normal controls; the others were patients with epilepsy. Except for water, starvation was absolute. Blood examinations were made every day in most cases, and every second or third day in some. The following substances were measured during some or all of the periods: in the blood, the total nonprotein, urea, amino-acid, uric acid and creatinin nitrogen, sugar, chlorid, calcium, phos phorus, cholesterol, and alkali reserve, and in the urine the total nitrogen, uric acid and hydrogen ion concentration. This paper deals only with the findings in regard to uric acid in the blood.
The effect of chemical ablation of the endocardium on ventricular fibrillation threshold.
Authors: R J Damiano, P K Smith, H F Tripp, T Asano, K W Small, J E Lowe, R E Ideker, J L Cox
Journal: Circulation (1986)

The purpose of this study was to examine the effects of ablation of the superficial endocardium and Purkinje network on left ventricular fibrillation threshold. Lugol's solution was applied through small ventriculotomies to the left and right ventricular endocardium of 10 dogs on cardiopulmonary bypass. Two control groups of five animals each underwent either endocardial application of saline or epicardial application of Lugol's solution. Ventricular fibrillation threshold was measured before and after each intervention by the single-stimulus technique. Application of Lugol's solution to the endocardium resulted in a 102 +/- 15% increase in ventricular fibrillation threshold from a control value of 26 +/- 2 to 53 +/- 6 mA (p less than .005). In two animals, ventricular fibrillation could not be initiated postoperatively. In the control groups, there were no significant changes in ventricular fibrillation threshold. Histologic examination revealed that Lugol's solution obliterated less than 0.5 mm of superficial endocardium while sparing the adjacent myocardium. Electrophysiologic and rheologic data confirmed the discrete nature of the chemical injury. Thus ablation of the superficial ventricular endocardium with Lugol's solution results in a profound increase in the ventricular fibrillation threshold with only minimal tissue destruction.
Lepirudin (Recombinant Hirudin) for Parenteral Anticoagulation in Patients With Heparin-Induced Thrombocytopenia
Authors: Andreas Greinacher, Uwe Janssens, Gunther Berg, Markus Böck, Harald Kwasny, Bettina Kemkes-Matthes, Petra Eichler, Heiko Völpel, Bernd Pötzsch, Matthias Luz
Journal: Circulation (1999)

Background —We prospectively investigated lepirudin for further parenteral anticoagulation in patients with heparin-induced thrombocytopenia (HIT). Methods and Results —Patients with confirmed HIT (n=112) received lepirudin according to need for 2 to 10 days (longer if necessary): A1, treatment: 0.4 mg/kg IV bolus, followed by 0.15 mg · kg −1 · h −1 intravenous infusion, n=65; A2, treatment in conjunction with thrombolysis: 0.2 mg/kg, followed by 0.10 mg · kg −1 · h −1 , n=4; and B, prophylaxis: 0.10 mg · kg −1 · h −1 , n=43. Outcomes from 95 eligible lepirudin-treated patients were compared with those of historical control patients (n=120). Complete laboratory response (activated partial thromboplastin time ratio &gt;1.5 with ≤2 dose increases and platelet count normalization by day 10) was achieved in 65 lepirudin-treated patients (69.1%; 95% CI, 59.3% to 78.3%). At 2 weeks after cessation of lepirudin, 11 patients died (9.8%), 10 underwent limb amputation (8.9%), and 20 suffered a new thromboembolic complication (17.9%). The average combined event rate per patient-day decreased from 5.1% in the pretreatment period to 1.5% in the treatment period. Thirty-five days after HIT confirmation, fewer lepirudin-treated patients than historical control patients had experienced ≥1 outcome (cumulative incidence 30.9% versus 52.1%; relative risk [RR] 0.71; P =0.12, log-rank test). Bleeding events were more frequent in the lepirudin group than the historical control group (cumulative incidence at 35 days, 44.6% versus 27.2%; RR 2.57; P =0.0001, log-rank test). No difference was observed in bleeding events requiring transfusion (cumulative incidence at 35 days, 12.9% versus 9.1%; RR 1.66; P =0.23, log-rank test); no intracranial bleeding was observed in the lepirudin group. Conclusions —Lepirudin effectively prevents death, limb amputations, and new thromboembolic complications and has an acceptable safety profile in HIT patients. Treatment should be initiated as soon as possible if HIT is suspected.
Converting enzyme inhibition after experimental myocardial infarction in rats: comparative study between spirapril and zofenopril
Authors: J. v. Wijngaarden, Y. M Pinto, W. H v. Gilst, P. A d. Graeff, C. D J d. Langen, H. Wesseling
Journal: Cardiovascular Research (1991)

The aim was to compare the effects of two novel angiotensin converting enzyme (ACE) inhibitors, spirapril and zofenopril, on cardiac remodelling in rats with congestive heart failure after myocardial infarction. Spirapril contains no sulphydryl group, whereas zofenopril is a sulphydryl containing ACE inhibitor.Experimental myocardial infarction was induced by ligation of the left coronary artery. Sham operated animals served as controls. Treatment with spirapril (2-2.5 mg.kg-1.d-1) or zofenopril (12-15 mg.kg-1.d-1) added to the drinking water was started immediately after myocardial infarction or sham operation and continued for six weeks. After the treatment period, all rats were killed. The heart was rapidly removed and perfused as described by Langendorff. Heart rate and left ventricular pressure were measured both at baseline and during stimulation with isoprenaline (6 nM). Heart and lung weights were determined.Normotensive male Wistar rats (220-240 g) were used.Experimental myocardial infarction considerably increased left ventricular cavity volume. Chronic treatment with either spirapril or zofenopril significantly attenuated this increase in volume. In infarcted rats, the increase in total heart and lung weight was also significantly reduced by chronic treatment with spirapril and zofenopril, indicating that these compounds reduce cardiac mass and pulmonary congestion in congestive heart failure due to myocardial infarction. There were no significant differences between treatment with spirapril and zofenopril. In the isolated and perfused rat heart, myocardial infarction significantly decreased both heart rate and left ventricular pressure. Converting enzyme inhibition only affected heart rate. Heart rate was significantly higher in infarcted animals treated with spirapril and zofenopril than in untreated infarcted animals.Both spirapril and zofenopril attenuated ventricular enlargement and cardiac hypertrophy in rats with congestive heart failure after myocardial infarction when treatment was started in the acute phase of myocardial infarction. No additional role could be attributed to the sulphydryl moiety of zofenopril. It is also suggested that these two ACE inhibitors modify cardiac sympathetic activity in rats with congestive heart failure, but more studies are needed to confirm these findings.
Study to evaluate manipulation therapy
Authors: Phil Gunby
Journal: JAMA (1983)

This summer marks the start of what could be the largest scientific effort yet to prove or disprove the usefulness of manipulation for treating back pain. The technique predates Hippocrates but to this day remains entangled in confusion and controversy. About 30 medical and osteopathic physicians and others researching manipulation will meet in Berne, Switzerland, Sept 11-17. Their goal: consensus on technique, on signs or symptoms that may call for or contraindicate manipulation, and even on terminology. The very word "manipulation," for example, does not have the same meaning for each of its practitioners. The American Association of Colleges of Osteopathic Medicine's latest<i>Glossary of Osteopathic Terminology</i>(Educational Council on Osteopathic Principles, 23 June 1982) lists 19 definitions under this heading. An abbreviated and general definition of manipulation might state that it involves various manual techniques of passive (the patient not actively participating) or active (patient moving in one direction