tbuckley/cabot-search huggingface dataset:
Higher adenoma detection rates with cap-assisted colonoscopy: a randomised controlled trial
Authors: Amit Rastogi, Ajay Bansal, Deepthi S Rao, Neil Gupta, Sachin B Wani, Tracy Shipe, Srinivas Gaddam, Vikas Singh, Prateek Sharma
Journal: Gut (2011)

<h3>Objective</h3> Cap-assisted colonoscopy (CAC) uses a small plastic transparent cap attached to the tip of the colonoscope that can depress and flatten colonic folds and thus improve visualisation of their proximal aspects. The aim of this study was to compare CAC with standard colonoscopy (SC; high-definition white light) for adenoma detection rates. <h3>Design</h3> This is a prospective randomised controlled trial. <h3>Setting</h3> The study was performed in a tertiary-care Veterans Affairs Medical Center in the USA. <h3>Patients</h3> Subjects undergoing screening or surveillance colonoscopy were enrolled. <h3>Interventions</h3> Subjects were randomised to undergo either CAC or SC. <h3>Main outcome measures</h3> The outcome measures were the proportion of subjects with at least one adenoma, the number of adenomas detected per subject, insertion time, caecal intubation rates and complications. <h3>Results</h3> 420 subjects were enrolled and included in the study (210 in each group). The proportion of subjects with at least one adenoma was higher with CAC compared to SC (69% vs 56%, p=0.009). CAC also detected a higher number of adenomas per subject (2.3 vs 1.4, p&lt;0.001). The caecal intubation time was shorter with CAC (3.29 min vs 3.98 min, p&lt;0.001). The caecal intubation rates were similar in the two groups (99% vs 98%, p=0.37). There were no complications associated with CAC or SC. <h3>Conclusions</h3> CAC detected a 13% higher number of subjects with at least one adenoma and 59% higher adenomas per subject. CAC is a safe, effective and practical means to improve adenoma detection rates. <h3>Clinical Trial Registration</h3> NCT 01211132.
Cardiac Arrhythmias Induced by Minimal Doses of Epinephrine in Cyclopropane-Anesthetized Dogs
Authors: PETER B. DRESEL, KEITH L. MacCANNELL, MARK NICKERSON
Journal: Circulation Research (1960)

Very small doses (0.1 to 2.0 µg./Kg.) of epinephrine injected in 1 minute into dogs anesthetized with 20 per cent cyclopropane cause a coupled rhythm which is usually bigeminal and characterized by an exceptionally constant interval between the coupled beats. Phenyiephvine also causes this arrhythmia, methoxamine does so rarely, but isoproterenol does not. An elevation in systolic pressure and possibly a tachycardia are required for the appearance of bigeminy. However, this arrhythmia can be elicited consistently by these factors only in the presence of a sympathomimetic amine with cardiac stimulant actions. A focus of automaticity has been ruled out in the genesis of the abnormal ventricular beat by demonstrating the constancy of the coupling interval despite sudden changes in the atrial rate. Dichloroisoproterenol appears to attenuate the induction of bigeminy by epinephrine to a considerably lesser extent than the major arrhythmias expected on injection of large doses of this sympathomimetic.
Suppressor of cytokine signaling-3 is a biomechanical stress–inducible gene that suppresses gp130-mediated cardiac myocyte hypertrophy and survival pathways
Authors: Hideo Yasukawa, Masahiko Hoshijima, Yusu Gu, Tomoyuki Nakamura, Sylvain Pradervand, Toshikatsu Hanada, Yasushi Hanakawa, Akihiko Yoshimura, John Ross, Kenneth R. Chien
Journal: Journal of Clinical Investigation (2001)

The gp130 cytokine receptor activates a cardiomyocyte survival pathway during the transition to heart failure following the biomechanical stress of pressure overload. Although gp130 activation is observed transiently during transverse aortic constriction (TAC), its mechanism of inactivation is largely unknown in cardiomyocytes. We show here that suppressor of cytokine signaling 3 (SOCS3), an intrinsic inhibitor of JAK, shows biphasic induction in response to TAC. The induction of SOCS3 was closely correlated with STAT3 phosphorylation, as well as the activation of an embryonic gene program, suggesting that cardiac gp130-JAK signaling is precisely controlled by this endogenous suppressor. In addition to its cytoprotective action, gp130-dependent signaling induces cardiomyocyte hypertrophy. Adenovirus-mediated gene transfer of SOCS3 to ventricular cardiomyocytes completely suppressed both hypertrophy and antiapoptotic phenotypes induced by leukemia inhibitory factor (LIF). To our knowledge, this is the first clear evidence that these two separate cardiomyocyte phenotypes induced by gp130 activation lie downstream of JAK. Three independent signaling pathways, STAT3, MEK1-ERK1/2, and AKT activation, that are coinduced by LIF stimulation were completely suppressed by SOCS3 overexpression. We conclude that SOCS3 is a mechanical stress–inducible gene in cardiac muscle cells and that it directly modulates stress-induced gp130 cytokine receptor signaling as the key molecular switch for a negative feedback circuit for both myocyte hypertrophy and survival.
Chemiluminescence response of human natural killer cells. I. The relationship between target cell binding, chemiluminescence, and cytolysis.
Authors: S L Helfand, J Werkmeister, J C Roder
Journal: The Journal of Experimental Medicine (1982)

The binding of tumor cells or fetal fibroblasts to human natural killer (NK) cells led to a rapid chemiluminescence response within seconds of target-effector interaction. The degree of chemiluminescence was dependent on the concentration of NK-enriched lymphocytes or target cells, and plasma membrane vesicles from K562 also induced a chemiluminescence response. Mild glutaraldehyde treatment of effector cells abrogated their ability to generate chemiluminescence, whereas K562 target cells treated in the same way were almost fully able to induce a chemiluminescence response to NK-enriched lymphocytes. These results show a directionality of response with NK as the responders and tumor cells as the stimulators. A survey of eight different tumor cell lines and fetal fibroblast lines revealed a striking correlation (r greater than 0.93, P less than 0.001) between the ability of a given line to bind to NK-enriched lymphocytes, induce chemiluminescence, and to be lysed. Three differentiated sublines of K562 grown in butyrate and cloned induced little chemiluminescence compared with the K562 parent, and they were selectively resistant to NK-mediated binding and cytolysis. In addition, treatment of K562 cells with higher concentrations of glutaraldehyde for longer periods led to varying degrees of target antigen preservation, as measured in cold target competition assays and in conjugate formation. The degree of NK target antigen preservation correlated directly with the ability of the cells to induce chemiluminescence (r greater than 0.95). The degree of NK activation was also important because interferon-pretreated effectors generated more chemiluminescence upon stimulation with K562 or MeWo targets. Monocytes or granulocytes did not contribute to the chemiluminescence induced by NK-sensitive targets. Some NK-resistant tumor cell lines were sensitive to monocyte-mediated cytolysis and also induced chemiluminescence in monocytes but not NK cells. These results show that the target structures recognized by the NK cell may play a role in NK activation because the degree of chemiluminescence was directly proportional to the ability of a given target cell line to bind to the NK cell and to be lysed.
Selective enhancement of GM-CSF, TNF-alpha, IL-1 beta and IL-8 production by monocytes and macrophages of asthmatic subjects
Authors: MP Hallsworth, CP Soh, SJ Lane, JP Arm, TH Lee
Journal: European Respiratory Journal (1994)

Previous work has demonstrated an increase in the production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by monocytes derived from asthmatic individuals. We have suggested that monocytes and macrophages enhance airways inflammation by augmented cytokine production. We tested this hypothesis by measuring the production of GM-CSF and macrophage-derived cytokines, namely interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8), from unstimulated and lipopolysaccharide (LPS)-stimulated peripheral blood monocytes and alveolar macrophages in 31 asthmatic and 11 normal, control subjects. The basal production of GM-CSF was four fold higher in the monocytes of asthmatic individuals, but there was no significant difference in the basal production of TNF-alpha, IL-1 beta and IL-8. After stimulation with LPS, asthmatic monocytes produced twofold more GM-CSF and fourfold more IL-1 beta than the monocytes from control subjects. Unstimulated macrophages from asthmatic subjects produced significantly less GM-CSF and TNF-alpha than macrophages from controls, and there was no difference in either IL-1 beta or IL-8 production. When stimulated by LPS, macrophages from asthmatic subjects produced twofold more GM-CSF, threefold more TNF-alpha and fourfold more IL-8. The levels of IL-8 produced by both monocytes and macrophages were at least 20 fold higher than those of the other cytokines measured. There is selectivity in the upregulation of cytokine production by monocytes and macrophages in asthma.(ABSTRACT TRUNCATED AT 250 WORDS)
Immunoglobulin Isotype Determines Pathogenicity in Antibody-Mediated Myocarditis in Naïve Mice
Authors: Anita P. Kuan, Lionel Zuckier, Li Liao, Stephen M. Factor, Betty Diamond
Journal: Circulation Research (2000)

Antimyosin reactivity is associated with cardiac damage in autoimmune myocarditis, an inflammatory heart disease characterized by a cellular infiltrate in the myocardium and myocyte necrosis. We are interested in the pathogenicity of antimyosin antibodies and their ability to cause autoimmune myocarditis. We have shown that antimyosin antibodies of the IgG isotype will induce disease in the DBA/2 mouse. In the present study, we show that IgM antimyosin antibodies do not induce myocarditis; however, these same antibodies become pathogenic when converted to the IgG isotype. Although IgM antibodies can penetrate the myocardium during cardiac inflammation, they are usually less able to leave the vascular compartment and penetrate cardiac tissue, thus accounting for their lack of pathogenicity. Thus, antimyosin B cells may be potentially pathogenic only after antigen activation and heavy chain class switching or under conditions that alter vascular permeability in the heart.
Use of Psychotropic Medications Before and After Sept. 11, 2001
Authors: Benjamin G. Druss, Steven C. Marcus
Journal: American Journal of Psychiatry (2004)

This study examined patterns of psychotropic medication use after the Sept. 11, 2001, terrorist attacks.It drew from two large pharmacy data sets, one providing nationally representative aggregate projections for all U.S. prescriptions (156.9 million claims for psychotropic medications during the study period) and a second from the nation's largest pharmacy benefit management organization (36.4 million enrollees per month), 4.1% of whom had a prescription for a psychotropic medication during the study period. Analyses examined use of antidepressant, antipsychotic, anxiolytic, and hypnotic medications in the 12 weeks before and after Sept. 11, 2001, compared with the same weeks during 2000.Nationally and in Washington, D.C., there was no evidence of an increase in overall prescriptions, new prescriptions, or daily doses for psychotropic medications. In New York City, there was an increase in the proportion of existing users with psychotropic dose increases in the weeks after the attacks (16.9% in 2001 versus 13.6% in 2000) but no significant increase in the rate of new psychotropic prescriptions.For most of the nation, the distress associated with the terrorist attacks was not accompanied by a commensurate increase in the use of psychotropic medications. In New York City, there was a statistically significant but modest increase in the proportion of individuals with dose increases in their psychotropic medications.
Pharmacological Characterization of Leukotriene Receptors
Authors: SVEN-ERIK DAHLÉN
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Whereas inhibition of 5-lipoxygenase will result in global inhibition of the production of leukotrienes, antagonism of leukotrienes at their tissue receptors provides selective inhibition of actions mediated by distinct classes of receptors (Table 1). The different profiles of biological activities for leukotriene B 4  (LTB 4 ) and the cysteinyl-leukotrienes suggested that the two main classes of leukotrienes possessed different classes of receptors, and pharmacological investigations have indeed confirmed this. The receptors for LTB 4  are called BLT receptors whereas the receptors for cysteinyl-leukotrienes are designated CysLT receptors (1). With regard to antagonism of the CysLT receptors, studies support some heterogeneity and at least two main subgroups of receptors have therefore been proposed, CysLT 1  and CysLT 2 . It is likely that there are more subdivisions to consider, but as the CysLT receptors remain to be cloned, this classification so far remains the framework for our understanding. Although there are experimental compounds that may block several of the known leukotriene receptors (Table 1), clinically useful drugs have so far been developed only against the main receptor for cysteinyl-leukotrienes in the human lung. This receptor is now called the CysLT 1  receptor but was previously known as the LTD 4 receptor. This article serves to give an overview of the leukotriene receptors, with particular attention to the virgin state of knowledge in this area.
Abnormally sustained aldosterone secretion during salt loading in patients with various forms of benign hypertension; relation to plasma renin activity
Authors: R. Dennis Collins, Myron H. Weinberger, Anne J. Dowdy, George W. Nokes, Carol M. Gonzales, John A. Luetscher
Journal: Journal of Clinical Investigation (1970)

Among 25 patients with benign, essential hypertension, and an equal number with other benign forms of hypertension, without serious cardiac, renal, or cerebrovascular impairment, 41 cases failed to reduce aldosterone excretion rates into the normal range (less than 5 mug/day) on a daily intake of 300 mEq of sodium. The hypertensive patients excreted slightly less than the normal fraction of labeled aldosterone as acid-hydrolyzable conjugate. Secretion rates were significantly higher in the hypertensive patients than in normotensive controls taking the high-sodium intake. On a 10 mEq sodium intake, the increase in excretion and secretion rates of aldosterone in the hypertensive patients could be correlated with plasma renin activity (PRA). The patients with the least increase in PRA had subnormal increase in aldosterone secretion and excretion, while unusually large rises in aldosterone secretion accompanied high PRA, especially in the cases with increased plasma angiotensinogen induced by oral contraceptives. The persistence of inappropriately high aldosterone secretion in most hypertensive patients during sodium loading could be related to a higher PRA than that found in normotensive controls under comparable conditions. In other hypertensives, whose PRA was unresponsive to sodium depletion, there was no significant correlation between PRA and aldosterone output, and no known stimulus to aldosterone production was detected. Five obvious cases of hyperaldosteronism were found among the 16 low-renin patients. The cause of the nonsuppressible aldosterone production in the other low-renin cases remains to be determined.
Pharmacokinetics of low-dose carboplatin and applicability of a method of calculation for estimating individual drug clearance
Authors: M.C. Etienne, F. Leger, X. Pivot, E. Chatelut, R.J. Bensadoun, E. Guardiola, N. Renée, N. Magné, P. Canal, G. Milano
Journal: Annals of Oncology (2003)
National Prostate Cancer Screening Rates After the 2012 US Preventive Services Task Force Recommendation Discouraging Prostate-Specific Antigen–Based Screening
Authors: Michael W. Drazer, Dezheng Huo, Scott E. Eggener
Journal: Journal of Clinical Oncology (2015)

In 2012, the US Preventive Services Task Force (USPSTF) discouraged prostate-specific antigen (PSA) -based prostate cancer screening. Previous USPSTF recommendations did not appreciably alter prostate cancer screening. Therefore, we designed a trend analysis to determine the population-based impact of the 2012 recommendation.The nationally representative National Health Interview Survey was used to estimate the proportion of men age 40 years and older who saw a physician and were screened for prostate cancer in 2013. An externally validated 9-year mortality index was used to analyze screening rates based on remaining life expectancy. Screening rates from 2005, 2010, and 2013 were compared using logistic regression.PSA-based screening did not significantly change from 2010 to 2013 among 40- to 49-year-old men (from 12.5% to 11.2%; P = .4). Screening rates significantly declined in men age 50 to 59 years (from 33.2% to 24.8%; P < .01), age 60 to 74 years (from 51.2% to 43.6%; P < .01), and age 75 years or older (from 43.9% to 37.1%; P = .03). A large percentage of men were screened for prostate cancer despite a high risk (> 52%) of 9-year mortality, including approximately one third of men older than age 75 years. Approximately 1.4 million men age 65 years or older with a high risk (> 52%) of 9-year mortality were screened in 2013.Prostate cancer screening significantly declined among men older than age 50 years after the 2012 USPSTF guideline discouraging PSA-based screening. A significant proportion of men continue to be screened despite a high risk of 9-year mortality, including one third of men age 75 years and older.
New Strategies in Prostate Cancer: Translating Genomics into the Clinic
Authors: Himisha Beltran, Mark A. Rubin
Journal: Clinical Cancer Research (2012)

With the rapidly developing use of next-generation sequencing technologies, there has been a surge in our knowledge of the genomic landscape of prostate cancer and a movement toward developing a molecular subclassification system for the disease. With this new understanding comes great clinical potential, both for the development of biomarkers as well as new therapeutic targets. Herein, we highlight the potential clinical use of recent discoveries and how they fit into our current paradigm. We describe the challenges that lie ahead as we move from genomic sequencing toward routine clinical practice and adopt precision cancer care for patients with prostate cancer.
Vitamin D receptor regulates TNF-mediated arthritis
Authors: Karin Zwerina, Wolfgang Baum, Roland Axmann, Gisela Ruiz Heiland, Jörg H Distler, Josef Smolen, Silvia Hayer, Jochen Zwerina, Georg Schett
Journal: Annals of the Rheumatic Diseases (2011)

Objective Reduced vitamin D intake has been linked to increased susceptibility to develop rheumatoid arthritis (RA) and vitamin D deficiency is associated with increased disease activity in RA patients. The pathophysiological role of vitamin D in joint inflammation is, however, unclear. Methods To determine the influence of absent vitamin D signalling in chronic arthritis, vitamin D receptor (VDR)-deficient mice were crossed with human tumour necrosis factor (TNF) transgenic mice (hTNFtg), which spontaneously develop chronic arthritis. Results Clinical signs and symptoms of chronic arthritis were aggravated in hTNFtg mice lacking functional VDR signalling. Moreover, synovial inflammation was clearly increased in VDR −/− hTNFtg mice as compared to hTNFtg mice and was associated with an increased macrophage influx in inflamed joints. In vitro, VDR-deficient monocytes were proinflammatory and hyper-responsive to TNF stimulation associated with prolonged mitogen-activated protein kinase activation and cytokine secretion. Also, VDR −/− monocytes showed enhanced potential to differentiate into bone resorbing osteoclasts in vitro. In line, VDR −/− hTNFtg mice had significantly increased cartilage damage and synovial bone erosions. Conclusions VDR plays an important role in limiting the inflammatory phenotype in a mouse model of RA. Absent VDR signalling causes a proinflammatory monocyte phenotype associated with increased inflammation, cartilage damage and bone erosion.
Paraneoplastic Thrombocytosis in Ovarian Cancer
Authors: Rebecca L. Stone, Alpa M. Nick, Iain A. McNeish, Frances Balkwill, Hee Dong Han, Justin Bottsford-Miller, Rajesha Rupaimoole, Guillermo N. Armaiz-Pena, Chad V. Pecot, Jermaine Coward, Michael T. Deavers, Hernan G. Vasquez, Diana Urbauer, Charles N. Landen, Wei Hu, Hannah Gershenson, Koji Matsuo, Mian M.K. Shahzad, Erin R. King, Ibrahim Tekedereli, Bulent Ozpolat, Edward H. Ahn, Virginia K. Bond, Rui Wang, Angela F. Drew, Francisca Gushiken, Donald Lamkin, Katherine Collins, Koen DeGeest, Susan K. Lutgendorf, Wah Chiu, Gabriel Lopez-Berestein, Vahid Afshar-Kharghan, Anil K. Sood
Journal: New England Journal of Medicine (2012)

The mechanisms of paraneoplastic thrombocytosis in ovarian cancer and the role that platelets play in abetting cancer growth are unclear.We analyzed clinical data on 619 patients with epithelial ovarian cancer to test associations between platelet counts and disease outcome. Human samples and mouse models of epithelial ovarian cancer were used to explore the underlying mechanisms of paraneoplastic thrombocytosis. The effects of platelets on tumor growth and angiogenesis were ascertained.Thrombocytosis was significantly associated with advanced disease and shortened survival. Plasma levels of thrombopoietin and interleukin-6 were significantly elevated in patients who had thrombocytosis as compared with those who did not. In mouse models, increased hepatic thrombopoietin synthesis in response to tumor-derived interleukin-6 was an underlying mechanism of paraneoplastic thrombocytosis. Tumor-derived interleukin-6 and hepatic thrombopoietin were also linked to thrombocytosis in patients. Silencing thrombopoietin and interleukin-6 abrogated thrombocytosis in tumor-bearing mice. Anti-interleukin-6 antibody treatment significantly reduced platelet counts in tumor-bearing mice and in patients with epithelial ovarian cancer. In addition, neutralizing interleukin-6 significantly enhanced the therapeutic efficacy of paclitaxel in mouse models of epithelial ovarian cancer. The use of an antiplatelet antibody to halve platelet counts in tumor-bearing mice significantly reduced tumor growth and angiogenesis.These findings support the existence of a paracrine circuit wherein increased production of thrombopoietic cytokines in tumor and host tissue leads to paraneoplastic thrombocytosis, which fuels tumor growth. We speculate that countering paraneoplastic thrombocytosis either directly or indirectly by targeting these cytokines may have therapeutic potential. (Funded by the National Cancer Institute and others.).