tbuckley/cabot-search huggingface dataset:
University Clinical Teachers
Authors: R. P. Michael
Journal: BMJ (1966)

Sir,?A meeting of the senior academic staff holding honorary consultant posts was recently held at this Institute to discuss the present situation as regards our terms of service (27 August, Supplement, p. 116). I have been asked to convey the disquiet we feel at the present situation, and to request that further representations be made on our behalf to the University Grants Committee and the Minister of Education. We recognize that we are a very small section of the medical profession as a whole, but it is no exaggeration to say that upon us the standards of British academic medicine, both in its teaching and research aspects, very largely depend. Our contributions to medical knowledge are, perhaps, one of the most im portant factors in the maintenance of that high prestige that British medical research currently enjoys internationally. One result of this prestige is the increasing drain from our ranks to senior research and teaching posts overseas. By any yardstick of professional merit and ability one may care to choose?whether possession of higher qualifications, publica tions, contributions to international meetings, or the standard of clinical teaching and care found in our teaching hospitals?we believe that we do not compare unfavourably with our colleagues in the Health Service. Yet we find ourselves penalized in terms of salary by amounts ranging from ?500 to ?1,000 per annum because we are employed by a university and work in a teaching-hospital setting. We regard this situation as quite irrational and completely indefensible. All of us on this Committee, which com prises all the staff of this Institute affected, would be most grateful if a further represen tation could be made to the University Grants Committee and the Minister on our behalf ; this would help to rectify a matter which is causing deep disquiet and one which has been outstanding too long.?I am, etc., Richard P. Michael, Chairman, Senior Medical Teachers-and Research Staff Committee. Institute of Psychiatry, University of London.
Oxidized low density lipoproteins inhibit relaxations of porcine coronary arteries. Role of scavenger receptor and endothelium-derived nitric oxide.
Authors: F CTanner, GNoll, C MBoulanger, T FLüscher
Journal: Circulation (1991)

BACKGROUNDWe studied the effects of low density lipoprotein (LDL) on endothelium function.METHODS AND RESULTSPorcine epicardial and intramyocardial coronary arteries suspended in organ chambers for isometric tension recording were exposed to LDL for 2 hours and were then washed. In epicardial coronary arteries, oxidized LDL (30-300 micrograms/ml) but not native LDL or lysolecithin inhibited endothelium-dependent relaxations to serotonin, thrombin, and aggregating platelets (5,000-75,000/microliter). Endothelium-dependent relaxations to bradykinin and A23187 and endothelium-independent relaxations to SIN-1 were unaffected by oxidized LDL. In intramyocardial coronary arteries, oxidized LDL had no appreciable effect on relaxations to serotonin. The effect of oxidized LDL on the response to serotonin in epicardial coronary arteries was completely prevented by dextran sulfate (10 micrograms/ml). The inhibitory effect of oxidized LDL persisted in the presence of pertussis toxin. Similar to the lipoproteins, L-N...
Attenuation of ecto-5'-nucleotidase activity and adenosine release in activated human polymorphonuclear leukocytes.
Authors: MKitakaze, MHori, TMorioka, STakashima, TMinamino, HSato, MInoue, TKamada
Journal: Circulation Research (1993)

To examine whether activation of polymorphonuclear leukocytes attenuates release of adenosine through attenuation of their own ecto-5'-nucleotidase activity, human polymorphonuclear leukocytes were incubated with and without exposure to either N-formyl-methionyl-leucyl-phenylalanine (FMLP) or complement C5a. Ecto-5'-nucleotidase activity of polymorphonuclear leukocytes was attenuated by both FMLP and complement C5a (22.7 +/- 3.6 vs 9.7 +/- 2.6 nmol/min per 10(7) cells at 10(-6) M FMLP, P < .05; 21.5 +/- 2.2 vs 10.2 +/- 1.2 nmol/min per 10(7) cells at 5 x 10(-7) g/mL complement C5a, P < .001), whereas cytosolic 5'-nucleotidase activity was not affected by either FMLP or complement C5a. These reductions of ecto-5'-nucleotidase activity that were caused by both FMLP and complement C5a were dose and time dependent and were inhibited by superoxide dismutase. Desferrioxamine did not inhibit the decreases in ecto-5'-nucleotidase. In accordance with the decreases in ecto-5'-nucleotidase activity, release of adeno...
Preeminence of the left stellate ganglion in the long Q-T syndrome.
Authors: RCrampton
Journal: Circulation (1979)

In seven patients with Romano-Ward syndrome, stellate ganglion block or stimulation and pharmacologic interventions were made to assess their influence on duration of the O-T interval, electrical alteration of the T wave and ventricular tachydysrhythmias. Left stellate ganglion block and right stellate ganglion stimulation shortened Q-T interval, abolished alternans phenomena and suppressed tachydysrhythmias. Propranolol and phenytoin had a similar effect. In contrast, right stellate ganglion block, left stellate ganglion stimulation and prior administration of quinidine and procainamide had an opposite effect. These responses resemble observations in animal models which suggest that excessive or unopposed activity of the left, or subnormal activity of the right stellate ganglion, or both, account for the pathophysiologic manifestations of the long Q-T syndrome. They are also consistent with clinically correlated, cardiac neuropathologic findings in these patients. An analogous but acquired dysautonomia i...
Tumor Immune Microenvironment during Epithelial–Mesenchymal Transition
Authors: Mana Taki, Kaoru Abiko, Masayo Ukita, Ryusuke Murakami, Koji Yamanoi, Ken Yamaguchi, Junzo Hamanishi, Tsukasa Baba, Noriomi Matsumura, Masaki Mandai
Journal: Clinical Cancer Research (2021)

Abstract Epithelial–mesenchymal transition (EMT) has been shown to play a critical role in tumor development from initiation to metastasis. EMT could be regarded as a continuum, with intermediate hybrid epithelial and mesenchymal phenotypes having high plasticity. Classical EMT is characterized by the phenotype change of epithelial cells to cells with mesenchymal properties, but EMT is also associated with multiple other molecular processes, including tumor immune evasion. Some previous studies have shown that EMT is associated with the cell number of immunosuppressive cells, such as myeloid-derived suppressor cells, and the expression of immune checkpoints, such as programmed cell death-ligand 1, in several cancer types. At the molecular level, EMT transcriptional factors, including Snail, Zeb1, and Twist1, produce or attract immunosuppressive cells or promote the expression of immunosuppressive checkpoint molecules via chemokine production, leading to a tumor immunosuppressive microenvironment. In turn, immunosuppressive factors induce EMT in tumor cells. This feedback loop between EMT and immunosuppression promotes tumor progression. For therapy directly targeting EMT has been challenging, the elucidation of the interactive regulation of EMT and immunosuppression is desirable for developing new therapeutic approaches in cancer. The combination of immune checkpoint inhibitors and immunotherapy targeting immunosuppressive cells could be a promising therapy for EMT.
Paget's disease of bone.
Authors: A S Wierzbicki
Journal: BMJ (1993)

Some parallels can be drawn with certain hereditary tumour syndromes such as multiple endocrine neoplasia.Both are characterised by a focal or multifocal pattern of distribution, abnormal cellular proliferation, and a genetic component.The hereditary tumour syndromes are thought to result from an inherited mutation in one allele of a tumour suppresser gene and an acquired mutation in the other allele.4Almost 20 years have elapsed since Rebel first noted "virus-like" particles in pagetic osteoclasts, but the identity of these structures remains unclear and they are not specific to Paget's disease.5 Immunohistochemical and in situ hybridisation studies have yielded conflicting results, since at different times evidence has been presented to suggest that antigens or nucleic acids from measles virus, respiratory syncytial virus, or canine distemper virus might be present in pagetic tissue or cultured cells67 but no virus has been isolated from affected tissue.Several groups have now used the polymerase chain reaction to try to recover paramyxovirus sequences from pagetic bone.Colleagues and I found no evidence of measles virus, canine distemper virus, respiratory syncytial virus, or related paramyxoviruses in RNA ex- tracted from pagetic tissue,8 and M Birch et al recently reported similar findings.9Though canine distemper virus transcripts (and in one case measles virus also) have been isolated from pagetic tissue,' these data must be interpreted with caution in view of the possibility of external contamination, since the same group had previously worked with probes to both viruses during earlier in situ hybridisation studies.7 Finally, D Roodman et al recently re- ported finding measles virus transcripts in cells derived from cultured pagetic bone.9These contradictory data could perhaps be explained by different viruses having a role in different geographical areas.The powerful molecular techniques now avail- able should soon result in great advances in our understanding of Paget's disease.7'0An important immediate issue is to confirm whether paramyxo- virus sequences can consistently be isolated from pagetic tissue and, if so, to determine whether their presence is disease specific.
Synchronous occurrence of spontaneous localized calcium release from the sarcoplasmic reticulum generates action potentials in rat cardiac ventricular myocytes at normal resting membrane potential.
Authors: M CCapogrossi, S RHouser, ABahinski, E GLakatta
Journal: Circulation Research (1987)

Under certain conditions, spontaneous release of Ca2+ from the sarcoplasmic reticulum occurs in resting mammalian myocardium. In single rat ventricular myocytes, such spontaneous Ca2+ release appears localized rather than homogeneous. When the increase in cytosolic Ca2+ is present in a single locus within a cell, it causes a small depolarization, which, at the normal resting potential, is subthreshold for generating an action potential. However, when spontaneous Ca2+ release occurs simultaneously at more than a single discrete locus, the resultant sarcolemmal depolarization is augmented to levels that can induce an action potential, even when this depolarization begins at the normal resting membrane potential. Thus, the synchronous occurrence of multifocal localized increases in cytosolic Ca2+ due to spontaneous Ca2+ release from the sarcoplasmic reticulum within ventricular myocytes is a mechanism for abnormal automaticity.
Effects of chronic digitalization on cardiac and renal Na+ + K+-dependent adenosine triphosphate activity and circulating catecholamines in the dog.
Authors: B RNechay, R EJackson, M GZiegler, S LNeldon, J DThompson
Journal: Circulation Research (1981)

To extend our understanding of the mechanism of action of digitalis drugs, we studied electrocardiograms (ECGs), renal function, plasma concentrations of catecholamines, and myocardial and renal Na+ + K+-dependent adenosine triphosphate (Na+ + K+ ATPase) activity in chronically digitalized dogs. Five healthy, male, mongrel dogs received a therapeutic regimen of digoxin (0.1 mg/kg on day 1 in three divided doses followed by 0.025 mg/kg per day) orally for 2-4 months. This resulted in plasma digoxin concentrations of 1.1 to 4.7 ng/ml as determined by radioimmunoassay. Six control dogs received daily gelatin capsules by mouth. ECGs monitored throughout the study showed no changes. Digitalized dogs had elevated plasma norepinephrine concentrations (347 vs. 137 pg/ml in controls) and no change in plasma epinephrine concentrations. Digitalized dogs had elevated glomerular filtration rates (0.74 vs. 0.94 ml/min per g of kidney) without significant changes in renal handling of electrolytes and water. All of the a...
Screening for Lung Cancer
Authors: Myron R. Melamed
Journal: Annals of Internal Medicine (1989)

Letters and Corrections1 November 1989Screening for Lung CancerMyron R. Melamed, MD, Betty J. Flehinger, MDMyron R. Melamed, MDSearch for more papers by this author, Betty J. Flehinger, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-111-9-764_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor: We wish to compliment Dr. Eddy (1) on his thoughtful review and evaluation of the lung cancer screening programs that we and others have carried out. However, we come to somewhat different conclusions based on our own analysis of our data.The results of the sputum cytology and chest roentgenogram screening for early lung cancer, derived from the three National Cancer Institute (NCI) supported studies to which Dr. Eddy refers, are not easily amenable to analysis. It is well to bear in mind that all these studies were designed to assess the value of sputum cytology when...References1. Eddy D. Screening for lung cancer. Ann Intern Med. 1989;111:232-7. LinkGoogle Scholar2. FlehingerKimmelMelamed BMM. Natural history of adenocarcinoma-large cell carcinoma of the lung: conclusions from screening programs in New York and Baltimore. JNCI. 1988;80:337-44. CrossrefMedlineGoogle Scholar3. FlehingerKimmel BM. The natural history of lung cancer in a periodically screened population. Biometrics. 1987;43:127-44. CrossrefMedlineGoogle Scholar1. Eddy D. Screening for lung cancer. Ann Intern Med. 1989;111:232-7. LinkGoogle Scholar2. Hulka B. Cancer screening: degrees of proof and practical application. Cancer. 1988;62:1776-80. CrossrefMedlineGoogle Scholar3. MulshineTockmanSmart JMC. Considerations in the development of lung cancer screening tools. JNCI. 1989;81:900-6. CrossrefMedlineGoogle Scholar4. TockmanGuptaMyers MPJ. Sensitive and specific monoclonal antibody recognition of human lung cancer antigen on preserved sputum cells: a new approach to early lung cancer detection. J Clin Oncol. 1988;6:1685-93. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Thomas J. Watson Research Center Yorktown Heights, NY 10598 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDiagnostic results before and after introduction of autofluorescence bronchoscopy in patients suspected of having lung cancer detected by sputum cytology in lung cancer mass screeningStage I nonsmall cell lung carcinomaLung cancer screening in cigarette smokers in the province of Varese, ItalyEvaluation of a clinic-based screening program for lung cancer with a case-control design in Kanagawa, JapanEARLY DETECTION IN LUNG CANCERScreening for Lung CancerDavid M. Eddy, MD, PhD 1 November 1989Volume 111, Issue 9Page: 764-766KeywordsCancer screeningCell biologyLung and intrathoracic tumorsLung cancer screeningSputumThorax Issue Published: 1 November 1989 PDF downloadLoading ...
The effects on atrial electrophysiology and structure of surgically induced right atrial enlargement in dogs.
Authors: P ABoyden, B FHoffman
Journal: Circulation Research (1981)

We evaluated the relationship between susceptibility to arrhythmias caused by right atrial (RA) enlargement and alterations in transmembrane potentials and ultrastructure. RA enlargement was produced in eight dogs (TI) by excising the septal cusp of the tricuspid valve through a right atriotomy and constricting the pulmonary artery. This procedure resulted in RA dilation and hypertrophy. Four sham-operated dogs (S) also were studied. Neither TI nor S dogs developed spontaneous atrial arrhythmias. Atrial overdrive (OD) and premature stimulation (PS) were used to initiate and terminate arrhythmias. At 2 weeks and for 20 to 30 weeks after surgical preparation, TI dogs were more susceptible to arrhythmias than S dogs. The duration of arrhythmias exceeded 10 minutes more often in TI dogs than in S dogs. Sixty-one percent of all arrhythmias in the TI dogs had rates of 320-450 impulses/min, and electrogram and ECG characteristics of atrial flutter (type II rhythm), whereas no S dogs developed rhythms with these ...
Bioreactor-engineered cancer tissue-like structures mimic phenotypes, gene expression profiles and drug resistance patterns observed “in vivo”
Authors: Christian Hirt, Adam Papadimitropoulos, Manuele G Muraro, Valentina Mele, Evangelos Panopoulos, Eleonora Cremonesi, Robert Ivanek, Elke Schultz-Thater, Raoul A Droeser, Chantal Mengus, Michael Heberer, Daniel Oertli, Giandomenica Iezzi, Paul Zajac, Serenella Eppenberger-Castori, Luigi Tornillo, Luigi Terracciano, Ivan Martin, Giulio C Spagnoli
Journal: Biomaterials (2015)
Increased regional myocardial stiffness of the left ventricle during pacing-induced angina in man.
Authors: P DBourdillon, B HLorell, IMirsky, W JPaulus, JWynne, WGrossman
Journal: Circulation (1983)

The left ventricular diastolic pressure-volume relationship shifts upward during angina, but why this happens is not known. To assess regional myocardial stiffness, we studied 12 patients who had coronary artery disease using simultaneous left ventricular micromanometer pressure recording and M-mode echocardiography before and during angina induced by pacing tachycardia. All patients had two- or three-vessel coronary artery disease that involved the posterior left ventricular wall circulation and had positive pacing stress tests, i.e., development of angina and a postpacing rise in left ventricular end-diastolic pressure (15 +/- 3 to 31 +/- 6 mm Hg, p less than 0.001). A marked upward shift in the relationship between the diastolic left ventricular pressure and the posterior wall thickness (h) occurred after pacing tachycardia, but the change in left ventricular posterior wall end-diastolic thickness was minimal (8.9 +/- 2.1 to 9.2 +/- 2.1 mm, NS). After pacing, the peak rate of left ventricular posterior...
Stiffness of systemic arteries in patients with myocardial infarction. A noninvasive method to predict severity of coronary atherosclerosis.
Authors: THirai, SSasayama, TKawasaki, SYagi
Journal: Circulation (1989)

The static elastic properties of arterial tree (abdominal aorta and common carotid artery) were studied in 19 normal subjects and in 49 patients with myocardial infarction with an ultrasonic phase-locked echo-tracking system that allows continuous transcutaneous measurement of the arterial diameter. The stiffness index beta, which represented the mechanical properties in the arterial wall, was calculated from the relation between systemic blood pressure and the diameter of the artery. Patients with myocardial infarction underwent coronary angiography in their convalescent period to determine involved vessels. In 11 patients, coronary artery was patent; 15 patients had one-vessel disease, 12 had two-vessel disease, and the remaining 11 patients had three-vessel disease. In normal subjects, increasing age was associated with an increase in arterial stiffness. An average value of the stiffness index of the abdominal aorta was 8.58 +/- 3.02 (mean +/- SD) and that of common carotid artery was 9.17 +/- 2.22. In...
Circumferential myocardial shortening in the normal human left ventricle. Assessment by magnetic resonance imaging using spatial modulation of magnetization.
Authors: N RClark, NReichek, PBergey, E AHoffman, DBrownson, LPalmon, LAxel
Journal: Circulation (1991)

BACKGROUNDConventional cardiac imaging methods do not depict true segmental myocardial shortening, since they cannot determine segment length between fixed points in the myocardium.METHODS AND RESULTSWe used electrocardiographically gated magnetic resonance imaging with spatial modulation of magnetization to noninvasively tag the myocardium with dark stripes at uniform 7-mm intervals center to center at end diastole. We then determined end-systolic stripe separation and thereby calculated circumferential shortening. When end systole was not reached in the first image series, a second temporally overlapped series starting in late systole was used to determine late-systolic shortening. Septal, anterior, lateral, and inferior segments were assessed at endocardium, midwall, and epicardium on five midventricular short-axis sections each in 10 normal volunteers. A transmural gradient in circumferential shortening was observed, with the percentage of endocardial segment shortening consistently greater than epi...
Reduced myocardial reflow and increased coronary vascular resistance following prolonged myocardial ischemia in the dog.
Authors: J TWillerson, J TWatson, IHutton, G HTempleton, D EFixler
Journal: Circulation Research (1975)

Studies were performed to determine whether an alteration in coronary vascular resistance and a reduction in the reflow phenomenon occurred in the blood-perfused, heparinized canine heart after various periods of myocaridal ischemia. Regional myocardial blood flow was measured with radioactive microspheres. Proximal left anterior descending coronary artery blood flow was measured with a periarterial flow transducer. Reduced reflow to the ischemic portion of the left ventricle and increased resistance in the left anterior descending coronary artery were present after 120 minutes of myocardial ischemia. The reduction in reflow was specific to the subendocardium of the ischemic area. Saline and isosorbide dinitrate (Isordi) did not prevent the increase in coronary vascular resistance or the significant reduction in reflow to the subendocardial portion of the ischemic area. Hypertonic mannitol given so as to increase serum osmolality 40 mosmoles/kg prevented the increase in coronary vascular resistance and mo...
Asystolic episodes during pacemaker implantation.
Authors: E AAstrinsky, SFurman, JFlorio
Journal: Circulation (1981)

During normal rate programming of a pulse generator from slower to more rapid rates, intervals of output impulse suppression lasting 2 seconds plus the newly programmed interval to a maximum of 3.935 seconds are possible, and are a result of the pulse interval control system. These occur if programming falls within the susceptible window (the period between the existing interval and the new one) but will not take place if the programming command is given immediately after an output pulse. Four incidents with resulting ventricular asystole of up to 2.8 seconds are documented and explained. No significant clinical complications were observed.
Des-1-Asp-angiotensin II. Possible intrarenal role in homeostasis in the dog.
Authors: R HFreeman, J ODavis, T ELohmeier
Journal: Circulation Research (1975)

The relative effects of des-a-Asp-angiotensin 3I and angiotensin II on renal function, including renin secretion, were investigated in normal and sodium-depleted dogs. Intrarenal arterial infusion of the heptapeptide fragment into normal dogs at a rate which was calculated to increase blood levels by only 7 ng/100 ml decreased renal blood flow from 254 +/- 9 ml/min to 220 +/- 12 and 219 +/- 12 ml/min (P less than 0.01 for both values) after 10 and 30 minutes of infusion, respectively; renin secretion decreased from 502 +/- 214 ng/min to 253 +/- 109 and 180 +/- 53 ng/min (P less than 0.05 for both values). Infusion of angiotensin II at the same rate decreased renal blood flow from 251 +/- 26 ml/min to 224 +/- 22 and 220 +/- 16 ml/min (P less than 0.01 and 0.025, respectively) and decreased renin secretion from 374 +/- 25 ng/min to 166 +/- 76 and 131 +/- 37 ng/min (P less than 0.025 for both values). Neither peptide significantly changed mean arterial blood pressure, creatinine clearance, or excreted sodium...