tbuckley/cabot-search huggingface dataset:
Prospective Study of Cyclin D1 Overexpression in Barrett's Esophagus: Association With Increased Risk of Adenocarcinoma
Authors: K. Bani-Hani, I. G. Martin, L. J. Hardie, N. Mapstone, J. A. Briggs, D. Forman, C. P. Wild
Journal: JNCI Journal of the National Cancer Institute (2000)

Esophageal adenocarcinoma commonly arises from a precancerous condition, Barrett's esophagus, in which the normal squamous epithelium is replaced by a columnar cell-lined epithelium. Genetic alterations occurring in this process could serve as biomarkers for the risk of malignant progression, improve surveillance, and contribute to early diagnosis. We examined two potential biomarkers, cyclin D1 and p53, in a prospective cohort of Barrett's esophagus patients.A total of 307 patients were enrolled in an endoscopic surveillance cohort, and esophageal biopsy specimens were collected at each endoscopy. Incident cases of adenocarcinoma were matched to control patients within the cohort by duration of follow-up, age, sex, and length of columnar cell-lined epithelium at recruitment. Biopsy specimens were analyzed for cyclin D1 and p53 protein levels by immunohistochemistry. Statistical tests were two-sided.A total of 12 cases of adenocarcinoma occurred within the follow-up period, and tumor biopsy specimens from 11 cases stained positive for cyclin D1. Biopsy specimens from eight of these patients taken at recruitment also stained positive for cyclin D1. A case-control analysis of biopsy specimens obtained at recruitment revealed a statistically significantly increased risk of progression to adenocarcinoma in Barrett's esophagus patients whose biopsy specimens were cyclin D1 positive (odds ratio [OR] = 6. 85; 95% confidence interval [CI] = 1.57-29.91; P =.0106) but not in patients whose biopsy specimens were p53 positive (OR = 2.99; 95% CI = 0.57-15.76; P =.197).Cyclin D1-positive staining could be a useful biomarker in identifying Barrett's esophagus patients at high risk of esophageal adenocarcinoma. Given the complexity of genetic alterations in the natural history of this cancer, additional biomarkers will be required to increase the sensitivity and specificity of molecular diagnosis.
Amantadine-induced diastolic depolarization and automaticity in ventricular muscle.
Authors: J J Salata, J Jalife, J L Megna, G Alperovich
Journal: Circulation Research (1982)

We studied the cardiac effects of amantadine, an antiviral and anti-Parkinson drug. Amantadine hydrochloride (100--800 microM) produced significant changes in the electrophysiological properties of isolated ventricular muscle preparations from frog, rabbit, cat, dog, and calf. At relatively low concentrations (100--300 microM), the drug increased action potential duration, decreased action potential amplitude and maximum diastolic potential, and induced phase 4 depolarization. Amantadine also caused subthreshold diastolic depolarizations, apparent upon cessation of stimulation in all preparations studied. The amplitude of the diastolic depolarizations increased as a function of time and/or concentration of drug, eventually reached threshold, and spontaneous activity ensued. In the steady state, amantadine-induced spontaneous activity was rather stable, and the rate was dependent upon the amantadine and external potassium concentrations, as well as the membrane potential. In the absence of stimulation, amantadine-induced spontaneous activity occurred abruptly or could be triggered by a single stimulus, often occurring in a "bursting" fashion that appeared to originate from multiple discrete foci. All actions of amantadine were rapidly reversed upon washout. Propranolol had no effect on the actions of the drug. Amantadine-induced spontaneous activity was unaffected by lidocaine, diminished by TTX, and reduced or abolished by verapamil. The results indicate that amantadine can directly alter the membrane properties of ventricular muscle, possibly due to an effect on potassium conductance. Furthermore, amantadine can be used as a tool to study the ionic basis of ventricular automaticity and to model cellular mechanisms of ventricular rhythm disturbances.
Disruptive innovation as a driver of science and medicine
Authors: J. Larry Jameson
Journal: Journal of Clinical Investigation (2014)

Academic medicine is an ecosystem. Like any ecosystem, critical factors affecting sustainability include diversity, disruptive external forces, and natural selection. Perhaps the most important issue we must grapple with is the extent to which we can proactively shape the future of academic medicine versus being subject to the natural forces of change. In thinking about this question, I am reminded of a quote from Ludwig van Beethoven in response to circumstances beyond his control. Faced with impending deafness, Beethoven said, “I shall seize fate by the throat; it shall certainly not bend and crush me completely” (1). Like Beethoven, the leaders in academic medicine should not only be resilient, but we have an obligation to society to identify creative solutions so that we can fulfill the AAP mission, as stated by Sir William Osler in 1885, “to advance scientific and practical medicine” (2). Never before have we had such advanced tools and the fund of knowledge to solve the ills of society. Indeed, Osler would be stunned to see the resources available to us.
CD30-positive T-cell-rich pseudolymphoma induced by gold acupuncture
Authors: K.J. Kim, M.W. Lee, J.H. Choi, K.J. Sung, K.C. Moon, J.K. Koh
Journal: British Journal of Dermatology (2002)

Journal Article CD30‐positive T‐cell‐rich pseudolymphoma induced by gold acupuncture Get access K.J. Kim, K.J. Kim Department of Dermatology, Asan Medical Center, College of Medicine, University of Ulsan, 388‐1 Poongnap‐dong, Songpa‐gu, Seoul 138‐736, Korea Search for other works by this author on: Oxford Academic Google Scholar M.W. Lee, M.W. Lee Department of Dermatology, Asan Medical Center, College of Medicine, University of Ulsan, 388‐1 Poongnap‐dong, Songpa‐gu, Seoul 138‐736, Korea Mi Woo Lee. E‐mail: kimkj20@dreamwiz.com Search for other works by this author on: Oxford Academic Google Scholar J.H. Choi, J.H. Choi Department of Dermatology, Asan Medical Center, College of Medicine, University of Ulsan, 388‐1 Poongnap‐dong, Songpa‐gu, Seoul 138‐736, Korea Search for other works by this author on: Oxford Academic Google Scholar K.J. Sung, K.J. Sung Department of Dermatology, Asan Medical Center, College of Medicine, University of Ulsan, 388‐1 Poongnap‐dong, Songpa‐gu, Seoul 138‐736, Korea Search for other works by this author on: Oxford Academic Google Scholar K.C. Moon, K.C. Moon Department of Dermatology, Asan Medical Center, College of Medicine, University of Ulsan, 388‐1 Poongnap‐dong, Songpa‐gu, Seoul 138‐736, Korea Search for other works by this author on: Oxford Academic Google Scholar J.K. Koh J.K. Koh Department of Dermatology, Asan Medical Center, College of Medicine, University of Ulsan, 388‐1 Poongnap‐dong, Songpa‐gu, Seoul 138‐736, Korea Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 146, Issue 5, 1 May 2002, Pages 882–884, https://doi.org/10.1046/j.1365-2133.2002.04649.x Published: 01 May 2002 Article history Accepted: 14 October 2001 Published: 01 May 2002
Medication adherence and the risk of severe asthma exacerbations: a systematic review
Authors: Marjolein Engelkes, Hettie M. Janssens, Johan C. de Jongste, Miriam C.J.M. Sturkenboom, Katia M.C. Verhamme
Journal: European Respiratory Journal (2014)

The benefits of drug therapy for asthma have been well established, but adherence to treatment is poor, and this might be associated with an increased risk of asthma exacerbations. The aim of this study was to review the literature on the association between adherence to asthma controller treatment and risk of severe asthma exacerbations in children and adults. A systematic literature search was performed in PubMed, Embase and Web of Science, from inception until January 2014. Studies were included if data on the association between medication adherence and severe asthma exacerbations were presented. Quality was assessed using a modified version of the Newcastle–Ottawa Scale. The search yielded 2319 unique publications, of which 23 met the inclusion criteria and underwent data extraction and quality scoring. High levels of heterogeneity across studies with regard to adherence and exacerbation measurements, designs and analysis precluded a formal meta-analysis. Although effect measures varied widely, good adherence was associated with fewer severe asthma exacerbations in high-quality studies. Good adherence tended to be associated with lower risk of severe asthma exacerbations. Future studies should use standardised methodology to assess adherence and exacerbations, and should consider inhaler competence.
Effects of extracellular calcium and sodium on depolarization-induced automaticity in guinea pig papillary muscle.
Authors: B G Katzung
Journal: Circulation Research (1975)

Regenerative discharge of action potentials is induced in mammalian papillary muscles by passage of small depolarizing currents. In this paper, the effects of various extracellular calcium and sodium concentrations and of tetrodotoxin on this phenomenon were studied in guinea pig papillary muscles in a sucrose gap chamber. Phase 4 diastolic depolarization was found to be associated with an increase in membrane resistance. The slope of phase 4 depolarization was decreased by reductions in extracellular calcium or sodium concentration. The range of maximum diastolic potentials and the thresholds from which regenerative potentials arose were reduced, especially at the positive limit of potentials, by a reduction in either ion. It was concluded that both calcium and sodium influence diastolic depolarization and participate in the regenerative action potentials of depolarization-induced ventricular automaticity.
Production of Hypernatremia and Hyperosmolarity in the Diabetes Insipidus Dog Infused with Ringer's Solution
Authors: L. S. DREIFUS, J. STAMLER, I. J. LICHTON
Journal: Circulation Research (1959)

Infusion of isotonic Ringer's solution led to hypernatremia and plasma hyperosmolarity in diabetes insipidus dogs. This phenomenon suggests a safe and reliable test for diabetes insipidus which does not require collection of urine.
How, where and with whom? Physical activity context preferences of three adult groups at risk of inactivity
Authors: Nicola W Burton, Asaduzzaman Khan, Wendy J Brown
Journal: British Journal of Sports Medicine (2012)

Background Strategies to promote physical activity may be more successful if they reflect people's interests. Purpose To explore physical activity contexts preferred by three adult groups at risk of inactivity: older adults, those with low income and those with high body mass index (BMI). Methods Cross-sectional data were from a mail survey of 7873 adults aged 42–67 years. Respondents indicated the extent of disagreement or agreement with a preference for each of 14 contexts relating to format (eg, vigorous), location (eg, outdoors) and social setting (eg, done alone). Data were analysed using multilevel multinomial logistic regression. Adjusted OR and 95% CI are reported. Results Those aged 60–67 (vs 42–49) years had significantly higher odds to prefer activities with people of same age, and significantly lower odds to prefer activities that are at a fixed time with scheduled sessions, competitive, team-based or vigorous. Adults with low (vs high) income had significantly higher odds to prefer activities that are low cost, not just about exercise, team-based, supervised, skill-based or that can be done alone, and significantly lower odds to prefer vigorous or outdoor activities. Adults with BMI 30+ (vs&lt;25) had significantly higher odds to prefer activities that are supervised, with people the same sex, team-based, with people the same age, or at a fixed time with scheduled sessions. Conclusions These three groups had distinct preferences for how, where and with whom the physical activity is done. This information could be used by those who promote, design, deliver and evaluate physical activity opportunities.
Drugs, ligation or both for the prevention of variceal rebleeding?
Authors: M. Schepke
Journal: Gut (2009)

There is general consensus that patients surviving a first bleeding episode from oesophageal varices should receive rebleeding prophylaxis.1 Almost two decades ago, band ligation (EBL) proved to be the superior endoscopic procedure compared to injection sclerotherapy. Since then, EBL or drug treatment (non-selective beta-blocker ± nitrates) have become the two first-line treatment options in this situation.

Theoretically, it is attractive to combine these two procedures since both act via two different mechanisms: local obliteration of varices by banding immediately stops the blood flow in these vessels, while drugs lower portal pressure and the related risk of rebleeding. According to a recent meta-analysis addressing this issue, combined endoscopic and drug treatment appeared to be superior to either drugs or endoscopic treatment alone.2 However, the relevance of this meta-analysis is limited: the majority of trials included used sclerotherapy as endoscopic method which is clearly inferior to ligation and has therefore been abandoned for elective treatment of oesophageal varices. When looking at the trials using EBL, the only two fully published ones show that adding drugs to ligation further lowers the rebleeding rate (not mortality) compared to ligation alone.3 4 Consequently, some authors recommend combination of band ligation plus drugs as best option …
Regeneration of Glomerular Podocytes by Human Renal Progenitors
Authors: Elisa Ronconi, Costanza Sagrinati, Maria Lucia Angelotti, Elena Lazzeri, Benedetta Mazzinghi, Lara Ballerini, Eliana Parente, Francesca Becherucci, Mauro Gacci, Marco Carini, Enrico Maggi, Mario Serio, Gabriella Barbara Vannelli, Laura Lasagni, Sergio Romagnani, Paola Romagnani
Journal: Journal of the American Society of Nephrology (2008)

Depletion of podocytes, common to glomerular diseases in general, plays a role in the pathogenesis of glomerulosclerosis. Whether podocyte injury in adulthood can be repaired has not been established. Here, we demonstrate that in the adult human kidney, CD133+CD24+ cells consist of a hierarchical population of progenitors that are arranged in a precise sequence within Bowman's capsule and exhibit heterogeneous potential for differentiation and regeneration. Cells localized to the urinary pole that expressed CD133 and CD24, but not podocyte markers (CD133+CD24+PDX− cells), could regenerate both tubular cells and podocytes. In contrast, cells localized between the urinary pole and vascular pole that expressed both progenitor and podocytes markers (CD133+CD24+PDX+) could regenerate only podocytes. Finally, cells localized to the vascular pole did not exhibit progenitor markers, but displayed phenotypic features of differentiated podocytes (CD133−CD24−PDX+ cells). Injection of CD133+CD24+PDX− cells, but not CD133+CD24+PDX+ or CD133-CD24− cells, into mice with adriamycin-induced nephropathy reduced proteinuria and improved chronic glomerular damage, suggesting that CD133+CD24+PDX− cells could potentially treat glomerular disorders characterized by podocyte injury, proteinuria, and progressive glomerulosclerosis.
Self-reported quality of life of 8–12-year-old children with cerebral palsy: a cross-sectional European study
Authors: Heather O Dickinson, Kathryn N Parkinson, Ulrike Ravens-Sieberer, Giorgio Schirripa, Ute Thyen, Catherine Arnaud, Eva Beckung, Jérôme Fauconnier, Vicki McManus, Susan I Michelsen, Jackie Parkes, Allan F Colver
Journal: The Lancet (2007)
Keratinocyte growth factor is a growth factor for type II pneumocytes in vivo.
Authors: T R Ulich, E S Yi, K Longmuir, S Yin, R Biltz, C F Morris, R M Housley, G F Pierce
Journal: Journal of Clinical Investigation (1994)

Keratinocyte growth factor (KGF) administered as a single intratracheal injection causes a prominent dose-dependent proliferation of type II alveolar epithelial cells in the lungs of adult rats. The increase in mitotically active alveolar cells histologically appears as a micropapillary epithelial cell hyperplasia after 2 d and peaks after 3 d in the form of monolayers of cuboidal epithelial cells lining alveolar septae. Proliferating cell nuclear antigen immunohistochemistry confirmed the profound proliferative response induced by KGF. The hyperplastic alveolar lining cells contain immunoreactive surfactant protein B and are ultrastructurally noted to contain lamellar inclusions characteristic of surfactant-producing type II pneumocytes. Mild focal bronchiolar epithelial hyperplasia is noted but is much less striking than the proliferation of type II pneumocytes. Large airways are unaffected by KGF. Daily intravenous injection of KGF is also able to cause pneumocyte proliferation. The normal adult rat lung constitutively expresses both KGF and KGF receptor mRNA, suggesting that endogenous KGF may be implicated in the paracrine regulation of the growth of pneumocytes. In conclusion, KGF rapidly and specifically induces proliferation and differentiation of type II pneumocytes in the normal adult lung.
Effects of Off-Pump and On-Pump Coronary-Artery Bypass Grafting at 1 Year
Authors: André Lamy, P.J. Devereaux, Dorairaj Prabhakaran, David P. Taggart, Shengshou Hu, Ernesto Paolasso, Zbynek Straka, Leopoldo S. Piegas, Ahmet Ruchan Akar, Anil R. Jain, Nicolas Noiseux, Chandrasekar Padmanabhan, Juan-Carlos Bahamondes, Richard J. Novick, Prashant Vaijyanath, Sukesh Kumar Reddy, Liang Tao, Pablo A. Olavegogeascoechea, Balram Airan, Toomas-Andres Sulling, Richard P. Whitlock, Yongning Ou, Janice Pogue, Susan Chrolavicius, Salim Yusuf
Journal: New England Journal of Medicine (2013)

Previously, we reported that there was no significant difference at 30 days in the rate of a primary composite outcome of death, myocardial infarction, stroke, or new renal failure requiring dialysis between patients who underwent coronary-artery bypass grafting (CABG) performed with a beating-heart technique (off-pump) and those who underwent CABG performed with cardiopulmonary bypass (on-pump). We now report results on quality of life and cognitive function and on clinical outcomes at 1 year.
Alternative Splicing of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Is Associated With Plasma Low-Density Lipoprotein Cholesterol Response to Simvastatin
Authors: Marisa Wong Medina, Feng Gao, Weiming Ruan, Jerome I. Rotter, Ronald M. Krauss
Journal: Circulation (2008)

HMGCR(3-Hydroxy-3-methylglutaryl coenzyme A reductase), the direct target of statin inhibition, undergoes alternative splicing of exon 13, which encodes part of the statin-binding domain of the enzyme. We hypothesized that HMGCR alternative splicing might be related to the interindividual variation in plasma low-density lipoprotein cholesterol response to statin treatment.We measured mRNA expression of both the full-length and the alternatively spliced HMGCR transcript lacking exon 13 (HMGCRv_1) in 170 simvastatin-incubated immortalized lymphocyte cell lines derived from participants in the Cholesterol and Pharmacogenetics (CAP) study who were treated with simvastatin 40 mg/d for 6 weeks. Greater upregulation of HMGCRv_1 in vitro was significantly correlated (P<or=0.0001) with smaller in vivo reductions of plasma total cholesterol, low-density lipoprotein cholesterol, apoprotein B, and triglycerides and explained 6% to 15% of the variation in their response to treatment. In contrast, no significant relationship was found between expression of the full-length HMGCR transcript and in vivo response. By siRNA knockdown of the full-length transcript, we found that HMGCR enzyme activity measured in cells enriched in HMGCRv_1 was relatively resistant to statin inhibition, consistent with the association of increased alternative splicing with reduced statin response in the CAP study. In addition, we found that a common HMGCR single-nucleotide polymorphism (rs3846662) located within intron 13 was associated with variation in the proportion of HMGCR mRNA that is alternatively spliced.Variation in the production of an HMGCR isoform with reduced statin sensitivity is a determinant of interindividual differences in low-density lipoprotein cholesterol, apolipoprotein B, and triglyceride response to statin treatment.
Human acclimatization to altitude.
Authors: J. R. Brotherhood
Journal: British Journal of Sports Medicine (1974)

The decision to hold the 1968 Olympic Games at Mexico City -an altitude of 2,200 m (7,450 ft) - necessitated physiological research into the effect of this moderate altitude on muscular exercise and athletic performance.Pugh (1967) showed that a period of acclimatization of at least four weeks enabled lowland athletes to improve their performances at altitude.Since 1968 training at altitude has been increasingly used by sportsmen in an attempt to improve their performances at sea level.
Tight Glycemic Control in Critically Ill Patients—Reply
Authors: Djillali Annane, Julie Lejeune, Sylvie Chevret
Journal: JAMA (2010)

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