tbuckley/cabot-search huggingface dataset:
PMO-219 Higher than expected false negative CLO test in patients not taking PPI associated with regular alcohol intake and absence of endoscopic gastritis
Authors: F Tahir, S Arshad, R C Evans, S Ashraf, H Elfaki, M Purcell-Jones
Journal: Gut (2012)

<h3>Introduction</h3> <i>H pylori</i> has a prevalence of around 40%–50% in the UK.<sup>1</sup> Rapid urease test (CLO test) is commonly used in the endoscopy units around the UK to detect <i>H pylori</i>. False negative CLO test results are associated with early reading of the test and use of acid suppressing medication.<sup>2</sup> We assessed the reliability of CLO test and prevalence of false negative results. <h3>Methods</h3> Retrospective data analysis was performed by auditing case notes of 85 patients with positive histology for <i>H pylori</i>. CLO test was performed by using Kimberly-Clarke CLO test kit and the reading time was between 12 and 24 h. <h3>Results</h3> Male:Female ratio was 43:42. False negative CLO test was found in 37 patients (43.6%), out of which 21 (56.7%) were not taking PPI or stopped PPI for at least 2 weeks prior to the endoscopy. 16 (43.2%) patients in the false negative group were drinking alcohol regularly as compared to 11 (22.9%) in CLO positive group, while 28 (58.3%) in CLO positive group were non drinkers. Regular drinkers taking PPI before the test had a low percentage (3/12; 25%) of CLO positive results while non-drinkers not on PPI show a high percentage (28/36; 77.8%) for positive results [p=0.013]. Also, in patients who had false negative CLO test, approximately 45% of patients consume regular alcohol. Absence of gastritis was associated with a slightly higher rate of false negative CLO test result (27.1% vs 20.8% for CLO positive) [p=NS]. Use of PPI only showed to contribute to false negative CLO test in absence of gastritis endoscopically (70% in patients with no gastritis and taking PPI) [p=NS]. Smoking was not associated with false negative CLO test. <h3>Conclusion</h3> High incidence of false negative CLO test result in our study suggests that CLO alone might not be a reliable test even in patients not taking acid suppressing medication. Regular alcohol use may contribute to false negative CLO test results. Gastric histology is better than CLO test in patients who are regular alcohol drinkers and taking PPI but in whom OGD does not show gastritis. Further studies need to be done to consider role of targeted gastric biopsies to increase the yield of CLO test. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Fuccio L</b>, Laterza L, Zagari RM, <i>et al.</i> Treatment of <i>H. pylori</i> infection. <i>BMJ</i> 2008;<b>15</b>;337. 2. <b>Prince MI</b>, <i>et al.</i> The CLO test in the UK, inappropriate reading and missed results. <i>Eur J Gastroenterol Hepatol</i> 1999.
EULAR points to consider for conducting clinical trials in systemic lupus erythematosus
Authors: C Gordon, G Bertsias, J P A Ioannidis, J Boletis, S Bombardieri, R Cervera, C Dostál, J Font, I-M Gilboe, F Houssiau, T W J Huizinga, D Isenberg, C G M Kallenberg, M A Khamashta, J-C Piette, M Schneider, J S Smolen, G Sturfelt, A Tincani, R Van Vollenhoven, D T Boumpas
Journal: Annals of the Rheumatic Diseases (2008)

Systemic lupus erythematosus (SLE) is a complex multi-organ disease, characterised by relapses and remissions.ng a high-quality randomised controlled trial poses many challenges. We have developed evidenced-based recommendations for points to consider in conducting clinical trials in patients with SLE.The EULAR Task Force on SLE comprised 19 specialists and a clinical epidemiologist. Initially, the evidence for clinical trial end-points in SLE was evaluated and this has been reported separately. A consensus approach was developed by the SLE Task Force in formulating recommendations for points to consider when conducting clinical trials in SLE.The literature review revealed that most outcome measures used in phase 2/3 trials in SLE have not actually been validated in clinical trials, although other forms of validation have been undertaken. The final recommendations for points to consider for conducting clinical trials in SLE address the following areas: study design, eligibility criteria, outcome measures including adverse events, concomitant therapies for SLE and its complications.Recommendations for points to consider when conducting clinical trials in SLE were developed using an evidence-based approach followed by expert consensus. The recommendations should be disseminated, implemented and then reviewed in detail and revised using an evidence-based approach in about 5 years, by which time there will be further evidence to consider from current clinical trials.
NOTES ON AN INTERESTING CASE OF COLOUR BLINDNESS
Authors: A. R. Galloway
Journal: BMJ (1912)

UNDEI this term one would first associate the ossification of tlle adductors met with in horsemen, and which receives tlle special appellation of " rider's bone."Or, again, we mlay think of another common example occulring in the deltoid muscle, usually seen amongst soldiers, the "drill bone."These two coinditions are explained by the detachment of periosteal fibres consequent upon somiie straini; these fibres still continue to perform their functions, and so give rise to the bony formiiation found in the tendon of the muscle.Apart froni the foregoing, bony conditions occur- ring in either the tendons or m-iuscles are rarely nlet, so it may be of interest to record the hiistory and histology of thc following example.In the first place, allow me to state tllat I wisli to demonstrate not a.periosteal bony formationi, but an acttual ietamorphosis of tendon fibres inlto cancellouk bone. A. S., mate on a coal barge, six montlhs before lie camle
Delayed Apoptotic Cell Clearance and Lupus-like Autoimmunity in Mice Lacking the c-mer Membrane Tyrosine Kinase
Authors: Philip L. Cohen, Roberto Caricchio, Valsamma Abraham, Todd D. Camenisch, J. Charles Jennette, Robert A.S. Roubey, H. Shelton Earp, Glenn Matsushima, Elizabeth A. Reap
Journal: The Journal of Experimental Medicine (2002)

Mice lacking the membrane tyrosine kinase c-mer have been shown to have altered macro-phage cytokine production and defective phagocytosis of apoptotic cells despite normal phagocytosis of other particles. We show here that c-mer–deficient mice have impaired clearance of infused apoptotic cells and that they develop progressive lupus-like autoimmunity, with antibodies to chromatin, DNA, and IgG. The autoimmunity appears to be driven by endogenous antigens, with little polyclonal B cell activation. These mice should be an excellent model for studying the role of apoptotic debris as an immunogenic stimulus for systemic autoimmunity.
Haplotype of Signal Transducer and Activator of Transcription 3 Gene Predicts Cardiovascular Disease in Dialysis Patients
Authors: Lin Zhang, W.H. Linda Kao, Yvette Berthier-Schaad, Yongmei Liu, Laura Plantinga, Bernard G. Jaar, Nancy Fink, Neil Powe, Michael J. Klag, Michael W. Smith, Josef Coresh
Journal: Journal of the American Society of Nephrology (2006)

Signal transducer and activator of transcription 3 (<i>STAT3</i>) protein has been linked to cardiovascular disease (CVD) through multiple pathways in experimental and animal studies. <i>STAT3</i> gene variation was examined as a predictor of incident CVD in a subcohort of 529 incident white dialysis patients. Fifteen single-nucleotide polymorphisms of the <i>STAT3</i> gene were genotyped. Haplotypes were estimated using software PHASE 2.1, and associations with first CVD event were tested using Cox proportional hazards analysis. Adjusted global tests of haplotype association with incident CVD and inflammation markers were performed using permutated <i>P</i> value in R-package Haplo.score. An <i>a priori</i> specified additive genetic model was assumed for haplotype analysis. Both genotypes (four single nucleotide polymorphisms with <i>P</i> &lt; 0.001) and haplotypes (<i>P</i> = 0.002 overall) were associated with incident CVD. Two major haplotype blocks, blocks A and C, were identified. Compared with common haplotype A-1, A-3 was associated with a hazard ratio (HR) of 0.70 (95% confidence interval [CI] 0.51 to 0.94) for CVD events after adjustment for covariates including C-reactive protein (CRP) and interleukin 6. Compared with common haplotype C-1, C-3 was associated with an adjusted HR of 2.12 (95% CI 1.25 to 3.57) for CVD events. Associations were independent of inflammation markers, but IL-6 levels were 14% lower (geometric mean ratio 0.86; 95% CI 0.77 to 0.96) per copy of haplotype A-3 compared with haplotype A-1 in block A after adjustment for CRP and other risk factors (<i>P</i> = 0.008). Variation in the <i>STAT3</i> gene is associated with the risk for CVD among white dialysis patients independent of serum IL-6 and CRP levels.
Abstract 2140: Assessment of curcumin-induced apoptosis and detection of cancer stem cell-like subpopulations in human esophageal cancer cell lines
Authors: Taghreed N. Al Manaa, Michael E. Geusz, Roudabeh J. Jamasbi
Journal: Cancer Research (2011)

Abstract Curcumin, the major active ingredient of turmeric, has been shown to kill several types of malignant cells while it has little or no effect on normal cells, suggesting that it may be an effective therapeutic agent. Although some studies have investigated curcumin effects on esophageal cancer cell lines, no studies have characterized the curcumin-surviving cells, an important population that might show resistance to curcumin. There is increasing evidence that many cancers contain subpopulations that display stem cell characteristics. Cancer stem cells (CSCs) appear to play a central role in tumorigenesis, recurrence, metastasis, and resistance to cancer therapy. The aims of the current study were to assess curcumin-induced cell death and detect CSC subpopulations in six human esophageal cancer cell lines (TE-1, TE-8, KY-5, KY-10, YES-1, and YES-2). Aldehyde dehydrogenase-1A1 (ALDH1A1) expression was used as one marker for CSCs. To evaluate curcumin effects, the cell lines were exposed to 20-80 µM of curcumin for 30 hrs. In all six lines, cell death increased continuously with increasing dosage of curcumin based on a standard crystal violet assay. No cells survived at 80 µM, and the range of cell death across the six cell lines was 66 to 89% at 60 µM. To characterize the progeny of cells that survived curcumin, 1×105 cells from each line were exposed to 40-60 µM curcumin for 30 hours, and the colonies that formed from surviving cells were counted. The number of colonies present after 60 µM treatment varied between the cell lines (ranging from 8 to more than one hundred). The Yes-2 cell line did not survive at 60 µM, but produced 15 colonies after 40 µM treatment. Staining with an antibody against ALDH1A1 was used to compare CSC-like subpopulations within and among the original cells lines as well as cell lines established from the curcumin-treated lines. All cell lines were heterogeneous with respect to ALDH1A1 staining, revealing two subpopulations within each line. The intensity of staining was at least two times higher in the population considered to be CSCs. Interestingly, the curcumin-surviving cell lines showed a significant loss in the high-staining population compared to the untreated cells (T-test, p&amp;lt;0.05), suggesting that curcumin not only can kill cancer cells but also CSCs. Thus, esophageal CSCs appear to be highly sensitive to curcumin. Therefore, curcumin may be a more effective compound for esophageal cancer therapy than other chemotherapeutic agents. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2140. doi:10.1158/1538-7445.AM2011-2140
A conversation with Helen Hobbs
Authors: Ushma S. Neill
Journal: Journal of Clinical Investigation (2015)

Helen Hobbs, an HHMI investigator, professor at the University of Texas Southwestern Medical Center, and director of the Dallas Heart Study, is best known for her research focused on identifying genetic factors that predispose people to developing metabolic disorders and heart disease. By studying outliers in the Dallas Heart Study, Hobbs (Figure 1) uncovered a genetic defect responsible for low blood LDL cholesterol levels. This work on the target PCSK9 has led to a hotbed of drug development, with FDA approval likely this year. To hear Hobbs’s stories about being mortified by initially getting some Cs in high school, her love of the wide, open spaces in Texas, and how she considered a stint as a cruise ship doctor, find the full interview on the JCI website (https://www.jci.org/videos/cgms).
The Royal University of Ireland
Authors: C. F. Knight
Journal: BMJ (1883)

<h3>Abstract</h3> Reconstructing invasion routes of transposable elements (TEs), so far, required capturing an ongoing invasion with population samples from different geographic regions and time points. Here, we propose a more accessible approach. Abundantly occurring internal deletions of DNA transposons allow to trace the direction as well as the path of an invasion, even hundreds of generations after the spread of a TE. We validated this hypothesis with computer simulations and by accurately reproducing the route of the P-element invasion in <i>Drosophila melanogaster</i>. Finally, we used our method to shed light on the controversial hobo invasion in <i>D. melanogaster</i>. Our approach solely requires sequenced samples from extant populations and sequences of TEs of interest. Hence, DNA transposons in a wide range of model and non-model organisms may be analyzed. Our approach will further our understanding of TE dynamics, migration patterns, and the ecology of species.
Preventing Cardiovascular Complications of Acute Infection
Authors: Allan J. Walkey
Journal: Circulation (2014)

…this is an experimental verification of this medical concept, relatively new, suggesting that infections merit an important place in the etiology of human atheromatous arteritis...-Gilbert and Lion, 1889, Comptes Rendus Hebdomadairesdes Séances et Mémoires de la Société de Biologie 1 T he connections between infection and cardiovascular dis- ease have been postulated for at least 125 years, when Gilbert and Lion 1 observed that acute infection with the typhoid bacillus resulted in atherosclerotic changes to the rabbit aorta.In the past few decades, much work has investigated the role for chronic viral and atypical bacterial infections in the progression of atherosclerosis; however, trials of antibiotics as secondary prevention for cardiovascular events have been disappointing. 2 More recently, epidemiological studies demonstrated an association between acute infection and cardiovascular events, such as acute myocardial infarction, 3 stroke, 4 cardiomyopathy, 5 or atrial fibrillation.
Angiotensin II and Prostaglandin Interactions on Systemic and Renal Effects of L-NAME in Humans
Authors: PATRIZIA PERINOTTO, ALMERINA BIGGI, NICOLETTA CARRA, ANTONELLA ORRICO, GIUSEPPE VALMADRE, PIERPAOLO DALL'AGLIO, ALMERICO NOVARINI, ALBERTO MONTANARI
Journal: Journal of the American Society of Nephrology (2001)

For investigation of whether interactions between prostaglandins and angiotensin II modulate renal response to acute nitric oxide synthesis inhibition in humans, seven young volunteers who were kept on a 240-mM Na diet underwent four experiments with 90 min of infusion of 3.0 microg/kg.min(-1) NG-nitro-L-arginine methyl ester (L-NAME), each preceded by a 3-d treatment with placebo (PL), 50 mg of losartan (LOS), 75 to 125 mg of indomethacin (IND), or both drugs. Mean arterial pressure (MAP), GFR, effective renal plasma flow (ERPF), and Na excretion rate (UNaV) were measured at baseline and from 0 to 45 min and 45 to 90 min of L-NAME infusion. After PL, L-NAME reduced GFR by 5% at 45 min (P < 0.05) and by 9% at 90 min (P < 0.001), ERPF by 11 to 17% (P < 0.001), and UNaV by 28 to 45% (P < 0.001). MAP, unchanged at 45 min, rose by 5% (P < 0.001) at 90 min. LOS prevented pressor but not renal effects of L-NAME. With L-NAME+IND, MAP rose even at 45 min (+5%; P < 0.001 versus baseline) with a 10% rise at 90 min (P < 0.001). Changes in GFR (-13 to -20%), ERPF (-19 to -26%), and UNaV (-51 to -70%) were greater than those with L-NAME+PL or L-NAME+LOS (P < 0.05 to 0.001). With L-NAME+IND+LOS, MAP did not increase, and GFR, ERPF, and UNaV fell much less than with L-NAME+IND alone (P < 0.02 to 0.001) with no differences versus PL or LOS alone. Angiotensin II blockade does not affect renal changes caused by L-NAME but prevents their potentiation by prostaglandin inhibition. Thus, endogenous prostaglandins counteract renal actions of endogenous angiotensin II in Na-repleted humans even when nitric oxide synthesis is inhibited.
Early positron emission tomography (PET) restaging: a predictive final response in Hodgkin's disease patients
Authors: P.L. Zinzani, M. Tani, S. Fanti, L. Alinari, G. Musuraca, E. Marchi, V. Stefoni, P. Castellucci, M. Fina, M. Farshad, S. Pileri, M. Baccarani
Journal: Annals of Oncology (2006)
Vascular Hypertrophy and Increased P70S6 Kinase in Mice Lacking the Angiotensin II AT <sub>2</sub> Receptor
Authors: Marc Brede, Kerstin Hadamek, Lorenz Meinel, Frank Wiesmann, Jörg Peters, Stefan Engelhardt, Andreas Simm, Axel Haase, Martin J. Lohse, Lutz Hein
Journal: Circulation (2001)

Angiotensin II activates 2 distinct G protein-coupled receptors, the AT(1) and AT(2) receptors. Most of the known cardiovascular effects of angiotensin II are mediated by the AT(1) receptor subtype. The aim of the present study was to test whether deletion of the AT(2) receptor gene in mice (AT(2)-KO mice) leads to long-term functional or structural alterations in the cardiovascular system.In vivo pressure responses to angiotensin II or the alpha(1)-adrenergic receptor agonist phenylephrine were greatly enhanced in AT(2)-KO mice. Deletion of the angiotensin AT(2) receptor did not lead to a compensatory increase of the activity of the circulating renin-angiotensin system, and arterial blood pressure was identical in wild-type control mice (WT) and AT(2)-KO mice. Cardiac contractility as assessed by LV catheterization and by rapid MRI also did not differ between AT(2)-KO and WT mice. Isolated femoral arteries from AT(2)-KO mice, however, showed enhanced vasoconstriction to angiotensin II, norepinephrine, and K(+) depolarization compared with WT. Morphometric analysis of large and small femoral arteries revealed a significant hypertrophy of media smooth muscle cells. Phospho-P70S6 kinase levels were significantly increased in aortas from AT(2)-KO mice compared with WT mice. Treatment of mice with an ACE inhibitor for 8 weeks abolished the increased pressure responsiveness, vascular hypertrophy, and enhanced P70S6 kinase phosphorylation in AT(2)-KO mice.These results indicate that vascular AT(2) receptors inhibit the activity and, hence, hypertrophic signaling by the P70S6 kinase in vivo and thus are important regulators of vascular structure and function.
CDK4/6 and IGF1 Receptor Inhibitors Synergize to Suppress the Growth of p16INK4A-Deficient Pancreatic Cancers
Authors: Andreas M. Heilmann, Rushika M. Perera, Veronika Ecker, Brandon N. Nicolay, Nabeel Bardeesy, Cyril H. Benes, Nicholas J. Dyson
Journal: Cancer Research (2014)

Loss-of-function mutations in p16(INK4A) (CDKN2A) occur in approximately 80% of sporadic pancreatic ductal adenocarcinoma (PDAC), contributing to its early progression. Although this loss activates the cell-cycle-dependent kinases CDK4/6, which have been considered as drug targets for many years, p16(INK4A)-deficient PDAC cells are inherently resistant to CDK4/6 inhibitors. This study searched for targeted therapies that might synergize with CDK4/6 inhibition in this setting. We report that the IGF1R/IR inhibitor BMS-754807 cooperated with the CDK4/6 inhibitor PD-0332991 to strongly block proliferation of p16(INK4A)-deficient PDAC cells in vitro and in vivo. Sensitivity to this drug combination correlated with reduced activity of the master cell growth regulator mTORC1. Accordingly, replacing the IGF1R/IR inhibitor with the rapalog inhibitor temsirolimus broadened the sensitivity of PDAC cells to CDK4/6 inhibition. Our results establish targeted therapy combinations with robust cytostatic activity in p16(INK4A)-deficient PDAC cells and possible implications for improving treatment of a broad spectrum of human cancers characterized by p16(INK4A) loss.
The authors reply to comments on “The lymphocyte transformation test for the diagnosis of Lyme borreliosis has currently not been shown to be clinically useful.” Clin Microbiol Infect 2014;20:O786–O787
Authors: R.B. Dessau, V. Fingerle, J. Gray, K.-P. Hunfeld, B. Jaulhac, W. Kristoferitsch, G. Stanek, F. Strle
Journal: Clinical Microbiology and Infection (2014)
Schedule-Dependent Cytotoxic Synergism of Pemetrexed and Erlotinib in Human Non–Small Cell Lung Cancer Cells
Authors: Tianhong Li, Yi-He Ling, I. David Goldman, Roman Perez-Soler
Journal: Clinical Cancer Research (2007)

Abstract Purpose: This study was undertaken to select the optimal combination schedule of erlotinib and pemetrexed for the treatment of relapsed non–small cell lung cancer (NSCLC) using a panel of human NSCLC lines. Experimental Design: Human NSCLC cell lines, with variable expression of the known molecular determinants of erlotinib sensitivity, were exposed to pemetrexed and erlotinib using different schedules. Antitumor effect was measured by growth inhibition by cell count and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cell cycle distribution and apoptosis by flow cytometry, and expression of cell cycle mediators by immunoblots. The cytotoxic interaction between pemetrexed and erlotinib (i.e., synergistic, additive, or antagonistic) was determined by median effect analysis. Results: When cells were exposed to concurrent pemetrexed and erlotinib or sequential pemetrexed followed by erlotinib, cytotoxic synergism was observed in both erlotinib-sensitive and erlotinib-resistant human NSCLC cell lines. This was independent of the mutation status of epidermal growth factor receptor or K-Ras genes. Synergism was associated with a combination of cell cycle effects from both agents. In contrast, exposure of cells to erlotinib followed by pemetrexed was mostly antagonistic in erlotinib-sensitive cells and additive at best in erlotinib-resistant cells. Antagonism was associated with erlotinib-induced G1-phase blockade of erlotinib-sensitive cells, which protects cells from pemetrexed cytotoxicity. Pemetrexed induced an epidermal growth factor receptor–mediated activation of the phosphatidylinositol 3-kinase/AKT pathway, which was inhibited by erlotinib and a specific phosphatidylinositol 3-kinase inhibitor, LY294002. Conclusions: The combination of pemetrexed and erlotinib is synergistic in NSCLC in vitro if exposure to erlotinib before pemetrexed is avoided, particularly in tumors that are sensitive to erlotinib. Based on these findings, a randomized phase II study comparing the progression-free survival between an intermittent combination of erlotinib and pemetrexed (experimental arm) and pemetrexed alone (control arm) in patients with relapsing NSCLC has been initiated.