tbuckley/cabot-search huggingface dataset:
Abstract 175: Lack of rDNA promoter hypomethylation in clinical prostate cancer specimens and cell lines
Authors: Motohide Uemura, Qizhi Zheng, William G. Nelson, Srinivasan Yegnasubramanian, Angelo M. De Marzo
Journal: Cancer Research (2010)

Abstract INTRODUCTION Alterations in the structure of nucleoli are hallmarks of prostate cancer cells. However, the molecular mechanisms that result in enlarged nucleoli in prostate cancer are unclear. The nucleolus is formed around tandem repeats (n=∼400) of the ribosomal RNA genes (18S, 5.8S and 28S) each of which contains an upstream promoter region. Only a limited number of repeat units are activated at any one time, and the inactive silent repeat units are characterized by dense methylation of the CpG island of the upstream promoter. While a previous study in liver cancer indicated that tumor cells contained hypomethylated CpG islands in the rDNA promoter, there are no prior studies in prostate cancer. Since MYC is overexpressed in most human PIN and prostate cancers, can affect nucleolar structure and activates rRNA transcription, we also addressed whether MYC levels affect rDNA promoter methylation. METHODS Genomic DNA was extracted from clinical samples of ten fresh frozen matched pairs of tumor and normal tissues obtained from radical prostatectomies, as well as, from 7 prostate cancer cell lines. Isolated DNA was subjected to sodium bisulfite sequencing of a region of the rDNA promoter, as well as, real-time methylation specific PCR. The functional role of MYC was explored by siRNA mediated knockdown in cell lines. RESULTS Most prostate cancer cell lines showed two roughly equal populations of the rDNA promoter region repeat units consisting of those that were densely methylated and those that were largely unmethylated. All clinical specimens were similar to the cell lines showing 2 populations with no changes in cancer compared to normal. After MYC knockdown in PC3 cells, there was an unexpected marked reduction in methylation of the rDNA promoter, despite decreased rRNA transcription. Chromatin immunoprecipitation (ChIP) followed by bisulfite sequencing revealed that MYC was bound nearly exclusively to the fully unmethylated promoters. CONCLUSIONS Clinical prostate cancer specimens, as well as most prostate cancer cell lines, do not show rDNA promoter hypomethylation. Thus, hypomethylation of the rDNA promoter does not explain why tumor nucleoli are enlarged. While MYC can activate transcription from unmethylated rDNA promoters, we show for the first time that it is unexpectedly required to maintain proper rDNA promoter methylation levels in the inactive repeat units. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 175.
Hyperoxic attenuation of exercise-induced bronchospasm in asthmatics.
Authors: P L Schiffman, A Ryan, B J Whipp, J E Hansen, K Wasserman
Journal: Journal of Clinical Investigation (1979)

To investigate the mechanism of exercise-induced bronchospasm, we measured specific airway conductance before and after exercise in 7 healthy normals, 12 asthmatics with intact carotid bodies, and 5 asthmatics who had had bilateral carotid body resection. The subjects breathed either air or oxygen (randomly assigned) during cycle ergometer exercise. Post-exercise bronchodilation was the usual pattern in normals, whereas post-exercise bronchospasm occurred in all asthmatics who breathed air during exercise. Oxygen breathing during exercise markedly attenuated the post-exercise bronchospasm in those asthmatics with intact carotid bodies, but had no significant effect in those without effect in those without carotid bodies. The attenuation of the bronchospasm with oxygen occurred with either incremental or constant load exercise of high intensity. The degree of attenuation did not correlate significantly with changes in end-tidal PCO2, maximum work rate, maximum exercise ventilation, or maximum heart rate. These studies indicate that oxygen attenuates exercise-induced bronchospasm in asthmatics through its action on the carotid bodies.
New Oral Anticoagulants for the Treatment of Venous Thromboembolism: Understanding Differences and Similarities
Authors: Paul P. Dobesh, John Fanikos
Journal: Drugs (2014)

Venous thromboembolism (VTE) is a major cause of morbidity, mortality, and healthcare expenditure. In the United States, approximately 0.1 % of the population experiences an initial VTE event each year. Anticoagulation therapy is the cornerstone of acute VTE treatment and for prevention of recurrent VTE events. Conventional anticoagulants, including heparin, low-molecular-weight heparins, fondaparinux, and vitamin K antagonists are widely used but have limitations. Newer oral anticoagulant agents, including direct thrombin inhibitors (e.g., dabigatran etexilate) and direct factor Xa inhibitors (e.g., rivaroxaban, apixaban, and edoxaban) have been developed to attempt to overcome some of the limitations of conventional anticoagulant therapy. These new oral agents have been evaluated for safety and efficacy in large, randomized clinical trials in the treatment and secondary prevention of VTE with results that are comparable to conventional therapy. Dabigatran, rivaroxaban, apixaban, and edoxaban are important new treatment options for patients with VTE. In this review, we compare these new agents and their associated clinical trials in VTE treatment.
A NEW 2H2O-METABOLIC LABELING METHOD REVEALS HETEROGENEOUS ALTERATIONS OF PROTEIN TURNOVER IN THE FAILING HEART
Authors: Felix J. Woitek, Ling Li, Jeffery Charles Powers, Marykathryn Hurst, Lien P. Ly, Anna M. Kulczycki, Amy Lam, Isabel Ottiger, Belinda Willard, William Stanley, Fabio A. Recchia, Takhar Kasumov
Journal: Journal of the American College of Cardiology (2014)
Should we screen for and treat childhood dyslipidaemia?
Authors: D. Kamerow
Journal: BMJ (2008)

The obesity epidemic raises the stakes in the issue of statins for children

It’s not an accident that evidence based guidelines more or less began with clinical preventive services. Unlike treatment for problems that produce symptoms, preventive medicine is optional. We have the luxury of time to gather and evaluate the evidence for the efficacy and even effectiveness of screening tests and counselling. When someone rushes into your surgery bleeding or doubled over in pain, it would hardly be acceptable to send them away untreated to await the results of a randomised controlled trial for their problem. But that is just what we do when people want to know whether they should undergo computed tomography to screen for lung cancer or be given vitamins to prevent heart disease. “Sorry,” we say, “insufficient evidence.”

And this is even truer for children—at least when the question is whether to screen them for early signs or symptoms of adult diseases. Firstly, we need to know whether the problem will even persist into adulthood. Secondly, do we have a safe and effective treatment? And most importantly, does treating the …
Growth of normal human hepatocytes in primary culture: Effect of hormones and growth factors on DNA synthesis
Authors: Tariq Ismail, John Howl, Mark Wheatley, Paul McMaster, James M. Neuberger, Alastair J. Strain
Journal: Hepatology (1991)

Although the ability of hormones and growth factors to stimulate DNA synthesis in rat hepatocytes has been investigated extensively, no such study of human hepatocytes has been reported. Here we describe a series of experiments to identify those factors that regulate human hepatocyte DNA synthesis in vitro and which therefore may play a role in the control of human liver regeneration. Human hepatocytes were isolated from normal liver tissue obtained after graft reduction for transplantation into pediatric recipients. Cells were maintained in culture for up to 5 days, and DNA synthesis was determined. Hydroxyurea reduced [3H]thymidine incorporation into DNA by 95%, indicating replicative DNA synthesis. As previously found with rat hepatocytes, epidermal growth factor and transforming growth factor-alpha stimulated DNA synthesis at low nanomolar concentrations; transforming growth factor-alpha was slightly more potent. Although the overall rate of thymidine incorporation was lower than that for rodent cells, human hepatocytes were sensitive to lower concentrations of these growth factors, and the degree of stimulation was similar. Conversely, transforming growth factor-beta inhibited DNA synthesis at low picomolar levels. By contrast (unlike rat hepatocytes), arginine-vasopressin failed to initiate or potentiate DNA synthesis in human cells. These data indicate that normal human hepatocytes can respond to low concentrations of growth promoters or inhibitors, previously shown to have activity on rat hepatocytes. These factors may then play a role in control of human liver growth. However, important species differences are apparent, highlighting the limitations of extrapolating from animal studies to humans.
Hepatocellular carcinomas in patients with metabolic syndrome often develop without significant liver fibrosis: A pathological analysis
Authors: Valérie Paradis, Stéphane Zalinski, Emna Chelbi, Nathalie Guedj, Françoise Degos, Valérie Vilgrain, Pierre Bedossa, Jacques Belghiti
Journal: Hepatology (2008)

Metabolic syndrome (MS) is a newly identified risk factor in chronic liver disease (CLD) and hepatocellular carcinoma (HCC). The aim of this study was to analyze the pathological characteristics of HCC and nontumoral liver in patients with MS as the only risk factor for liver disease in comparison with those that developed in the course of other CLDs in order to provide further insight into the physiopathology of HCC associated with MS. HCC patients with features of MS as the only risk factor for liver diseases (MS group, n = 31) were compared to HCC patients with overt causes of CLD (CLD group, n = 81) or without causes of CLD (cryptogenic group, n = 16) who underwent surgical resection during the same period of time. Among the patients of the MS group, there were 30 males and 1 female. In comparison with the patients with HCC of the CLD group, the patients with MS were older (mean age: 67+/- 7 versus 59 +/- 14 years, P < 0.01), and the background liver was significantly more often free of significant fibrosis (F0-F2: 65% in the MS group versus 26% in the CLD group, P < 0.001). In addition, HCCs associated with MS were more often well differentiated (65% versus 28%, P < 0.001). Five HCCs, all from the MS group, developed on a preexisting liver cell adenoma, with three of them showing typical histological features of telangiectatic adenoma.This study shows that HCCs in patients with features of MS as the only risk factor for liver disease have distinct morphological characteristics and mainly occur in the absence of significant fibrosis in the background liver. In addition, some of them arise through malignant transformation of a preexisting liver cell adenoma.
Management of Gastrointestinal Stromal Tumors : Experience of the Hassan II University Hospital, Fez, Morocco
Authors: Lamiae Amaadour, Zineb Benbrahim, Amarti Afaf, Khaled AIT Taleb, Khaled Maazaz, Adil Ibrahimi, Siham Tizniti, Samia Arifi, Nawfel Mellas, Omar El Mesbahi
Journal: Annals of Oncology (2013)
Gamma-glutamylcysteine ethyl ester for myocardial protection in dogs during ischemia and reperfusion
Authors: Shiro Hoshida, Tsunehiko Kuzuya, Nobushige Yamashita, Masashi Nishida, Shigehisa Kitahara, Masatsugu Hori, Takenobu Kamada, Michihiko Tada
Journal: Journal of the American College of Cardiology (1994)
The Care and Nurture of a Scholarly Faculty
Authors: Robert H. Alway
Journal: JAMA (1963)

MEDICAL CARE, education, and society are our concern. Whether we are here as practitioners, professors, investigators, or administrators, we all should be here as doctors, that is, as learned men and women and as teachers.  Patients, practitioners, and medical educators seem to be increasingly concerned about the patient-doctor relationship. This idea is not new, only recrudescent. It has been of concern throughout recorded history, going back at least to the Hippocratic corpus.  Students and teachers are preoccupied with their goals and the performances of themselves and each other. This, too, is not new. For instance, a small painting in the Louvre entitled La Melancolie, depicts the epitome of the student of medicine throughout the ages.  Our concern about medical education is, of course, but one facet of society's wish to have all education reexamined. This concern for educational processes and products, particularly the dissatisfactions of teachers with their lot, is
Hypouricemia in Hodgkin's Disease
Authors: JOEL S. BENNETT
Journal: Annals of Internal Medicine (1972)

Two patients with advanced Hodgkin's disease had persistent hypouricemia. Renal clearance studies showed elevated uric acid clearances of 35 and 23 ml/min, respectively. Only minimal abnormalities of other renal tubular functions were present. In both cases the abnormal renal handling of uric acid was corrected with therapy of the Hodgkin's disease, strongly suggesting that the disease was the causal factor. In one patient Hodgkin's disease and hypouricemia recurred, associated with a renal uric acid clearance of 20 to 25 ml/min, and studies with pyrazinamide were done. Assuming that pyrazinamide nearly completely blocks renal tubular secretion of uric acid in man, the study suggests that excessive secretion of uric acid was the cause of the serum and urine abnormalities.
SAT0208 Seven-Joint Power Doppler Ultrasound Score is Discordant to DAS28, SDAI and CDAI in Treatment Target Identification in Rheumatoid Arthritis Patients with Fibromyalgia
Authors: R. Chakr, M. Behar, J.A. Mendonça, A.L. Moro, D. Zanchet, I. Siqueira, V. Hax, A. Gasparin, P. Palominos, C. Kohem, C. Brenol, O. Monticielo, R. Xavier, J.C.T. Brenol
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> FM increases DAS28, SDAI and CDAI, misleading DMARD use and increasing costs and adverse events. (1,2) Seven-joint PDUS score is an objective measure of RA activity and, therefore, should not be influenced by FM. (3) <h3>Objectives</h3> To compare 7-joint PDUS score, DAS28, SDAI and CDAI as instruments to identify treatment target in RA patients with and without FM. <h3>Methods</h3> A transversal case-control study matched by RA duration and rheumatoid factor positivity was conducted from March 2012 through March 2013. Cases were RA patients with FM and controls were RA patients without FM, according to ACR classification criteria for RA (1987) and FM (1990). Cases and controls were consecutively recruited from a University-based RA clinic. DAS28, SDAI, CDAI and 7-joint PDUS scoring was blinded. Target discordance was defined as moderate or high disease activity in DAS28, SDAI or CDAI and a joint-level PDUS score ≤1. Medians (IQR) were compared by Mann-Whitney9s test. Two-tailed P values &lt;0.05 were considered significant. OR (95%CI) of RA target discordance due to FM was calculated for DAS28, SDAI and CDAI. <h3>Results</h3> Seventy-two RA women were included (36 with FM and 36 without FM). Median (IQR) age was 57.5 (49.3-66.8) years, RA duration was 13.0 (6.0-19.0) years and FM duration was 6.0 (2.0-15.0) years. Cases (RA with FM) and controls (RA without FM) had similar 7-joint PDUS scores 3.0 (1.0-5.8) vs. 4.0 (2.0-5.0), P=0.87, respectively. Cases had greater DAS28 [4.6 (3.3-5.8) vs. 3.3 (2.7-4.0), P&lt;0.001], SDAI [15.9 (10.7-28.9) vs. 8.3 (5.0-13.1), P&lt;0.001] and CDAI [15.3 (10.1-28.4) vs. 8.0 (4.2-12.9), P&lt;0.001] than controls. Cases and controls with DAS28-derived target discordance were 23 (64%) and 14 (39%), respectively [OR 2.8 (1.1-7.2)]. Cases and controls with SDAI-derived target discordance were 20 (56%) and 9 (25%), respectively [OR 3.8 (1.4-10.2)]. Cases and controls with CDAI-derived target discordance were 21 (58%) and 9 (25%), respectively [OR 4.2 (1.5-11.5)]. <h3>Conclusions</h3> The distortion of clinical RA treatment target caused by concomitant FM may be attenuated by 7-joint PDUS scoring. Longitudinal studies comparing 7-joint US score, DAS28, SDAI and CDAI are needed to demonstrate if an objective target improves RA treatment outcomes, by preventing overtreatment and decreasing adverse events and costs. <h3>References</h3> Arthritis Rheum. 2009 Jun 15;61(6):794-800 J Rheumatol. 2013 Dec;40(12):1977-85 Arthritis Rheum. 2009 Sep 15;61(9):1194-201 <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3306
Splenic Rupture in Leukemia
Authors: Anthony P. Tartaglia, William B. Scharfman, Simon Propp
Journal: New England Journal of Medicine (1962)

Rupture of the spleen in leukemia is exceedingly rare. The medical literature in English refers to only 12 such cases. In the period from 1948 through 1960, 291 patients with leukemia, which was acute in 176, were admitted to the Albany Medical Center Hospital. Splenic rupture occurred in 1 patient in 1960 and in 2 in 1961, all with acute leukemia. We believe that these cases are worthy of a report because of their rarity and because of the clinical problems presented.Abdominal pain, which is largely due to splenic infarction and perisplenitis, is not an infrequent complication in diseases . . .
Contradictions in Highly Cited Clinical Research
Authors: Colin P. West, Paul S. Heckerling, Peter Westfall, S. Stanley Young, John P.A. Ioannidis
Journal: JAMA (2005)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The Emergence of Geriatric Assessment Units
Authors: ARNOLD M. EPSTEIN
Journal: Annals of Internal Medicine (1987)

Previous studies have suggested that geriatric assessment units may provide important benefits to the care of elderly persons. In early 1985 we surveyed personnel at 104 (91%) of the existing 114 geriatric assessment units associated with medical schools and Veterans Administration medical centers for information on the units' development and operation. Although almost 80% of the units were hospital based, most (61%) provided care for outpatients. Nearly half (47%) began operation in 1983 or later; of those in existence before 1983, two thirds have increased their capacity since then. The types of personnel and their training differed substantially among units. Fifty percent of the physicians had had no formal training in geriatrics. Of the 104 units, 99 (95%) did routine assessment. The estimated time spent per new patient in outpatient units was 2.7 +/- 2.1 (SD) hours. These data suggest that geriatric assessment units are proliferating rapidly, have differing structures, and consume substantial resources. Further efforts are needed to define their optimal structure, targets, and function.
US health agency scales down plans for free, online research results
Authors: Zosia Kmietowicz
Journal: BMJ (2005)

The US health agency, the National Institutes of Health (NIH), has modified its plans to make the results of nationally funded research available free of charge after pressure from scientific publishers who claim the policy will damage their profits.

Instead of making the results available on a publicly accessible website within six months of publication in a scientific journal, as originally planned, the agency has extended the deadline for posting results to a year.

Many supporters of public access have …
Renal function in ascites: Position is everything in life
Authors: Asghar Rastegar
Journal: Hepatology (1986)

The assumption of upright posture by patients with liver cirrhosis leads to striking activation of adrenergic and renin-angiotensin systems. The tilting-induced modifications in renal function of eight healthy controls and 14 untreated patients with liver cirrhosis and ascites were related to plasma concentrations of noradrenaline, renin activity and aldosterone. All patients had preserved renal blood perfusion. All parameters were evaluated during bed rest for two hours and in the sitting posture for one hour. Basal plasma renin activity (0.1 &lt; p &lt; 0.05), aldosterone and noradrenaline concentrations (p ± 0.01) were raised in cirrhotics. The renal function tests (creatinine clearance, filtered sodium, tubular rejection fraction, urinary sodium excretion) were significantly reduced in cirrhosis. Under basal conditions, in cirrhotic patients tubular rejection fraction and urinary sodium excretion were inversely related to both noradrenaline and aldosterone concentrations. After tilting, the noradrenaline and aldosterone integrated outputs (ΣΔ) were significantly greater in cirrhosis. All renal function tests significantly decreased in cirrhotics, whereas creatinine clearance only significantly decreased in controls. Patient's tubular rejection fraction of sodium and sodium excretion were related to ΣΔ aldosteronaemia (r = −0.72; p &lt; 0.01), but no longer to ΣΔ plasma noradrenaline.
Star Wars: Defense or Death Star?
Authors: Jane M. Orient
Journal: JAMA (1986)

Recognizing the importance of the current debate about strategic defense, Physicians for Social Responsibility sponsors lecture tours by various experts, including Lt Col Robert M. Bowman, USAF (Retired). From 1976 to 1978, Bowman directed the Talon Gold project, which was concerned with the development of a pointer tracker system for a laser battle station. Bowman's position is summarized in the prologue: "Star Wars... would really be a Death Star system, capable of bringing about the destruction of the Planet Earth" (p v). The mechanism suggested by his image is the shattering of the globe by a directed energy burst, as in the movie<i>Star Wars</i>. The mechanism actually discussed is an arms race in space, which would, he argues, "guarantee" the outbreak of nuclear war. "Vulnerable defenses" (apparently in contrast to nonexistent ones) invite attack, in his opinion. Furthermore, Bowman declares that the "radical right" administration really wants an offensive
TCT-441 Enhanced Endothelial Tubule Formation in Response to Proly-Hydroxylase Inhibitor FG-2216: A Step Towards Therapeutic Angiogenesis in Chronic Total Occlusions
Authors: Georgina Barnett, Benjamin Wrigley, Damien Kelly, Emily Flashman, Christopher Schofield, Anthony Gershlick
Journal: Journal of the American College of Cardiology (2012)
A sore point
Authors: T. Dalrymple
Journal: BMJ (2010)

“It is strange,” wrote Sir William Osler in his brief essay on the French 18th century physician Jean Astruc, “how the memory of a man may float to posterity on what he would have himself regarded as the most trifling of his works.” So it was, and is, with Sir Henry Howarth Bashford (1880-1961).

Sir Henry was physician to George VI and for many years chief medical officer to the Post Office, in which capacity he demonstrated that 16 year old recruits to that great department of state were 1.5 inches taller, and weighed sixteen pounds more, in 1939 than recruits in 1914. He was also the first editor of the British Journal of Industrial Medicine …