tbuckley/cabot-search huggingface dataset:
Bronchoalveolar lavage in children
Authors: J de Blic, F Midulla, A Barbato, A Clement, I Dab, E Eber, C Green, J Grigg, S Kotecha, G Kurland, P Pohunek, F Ratjen, G Rossi
Journal: European Respiratory Journal (2000)

Bronchoalveolar lavage (BAL) is routinely performed in adults for sampling cellular and biochemical components.Many studies have been performed that have enabled the proposal of recommendations for BAL, methodology and processing, as well as reference values in different clinical settings.In contrast, despite a world-wide increase in the use of BAL in children, including neonates, there are, at the present time, no clear recommendations on the methodology, the clinical applications and the research areas for BAL.A Task Force on BAL in children has been approved by the European Respiratory Society (ERS) Task Force committee 1996.The objectives of this task force were: 1) to provide recommendations and guidelines on how to perform BAL and how to process the return fluid in children; 2) to collect and discuss available reference values; 3) to list indications and results in both immunocompetent and immunocompromised children; 4) to define areas for future research.This task force included paediatric respiratory physicians involved in bronchoscopy and BAL and was run as a collaboration between the Paediatric Bronchology Group
Longitudinal Tracking of Left Atrial Diameter Over the Adult Life Course: Clinical Correlates in the Community
Authors: David D. McManus, Vanessa Xanthakis, Lisa M. Sullivan, Justin Zachariah, Jayashri Aragam, Martin G. Larson, Emelia J. Benjamin, Ramachandran S. Vasan
Journal: Circulation (2010)

Increased left atrial diameter (LAD) is associated with elevated risk of atrial fibrillation (AF) and cardiovascular disease. Information is limited regarding the short- or long-term correlates of LAD.We evaluated clinical correlates of LAD for a 16-year period in 4403 Framingham Study participants (mean age, 45 years; 52% women; median observations/participant=3) using multilevel modeling. We related age, sex, body mass index (BMI), systolic and diastolic blood pressure (BP), diabetes, and antihypertensive treatment to LAD. Sex-specific growth curves for LAD were estimated for individuals with low, intermediate, and high risk factor burden. We also related risk factors to changes in LAD during a 4-year period in 3365 participants. Age, male sex (3.83 mm compared to women), greater BMI, higher systolic BP (0.24 mm per 10 mm Hg increment), and antihypertensive treatment (0.54 mm) were associated positively with LAD (P<0.001). Men had a greater increase in LAD with BMI than women (2.02 versus 1.77 mm in women, per 5-unit increment), and individuals receiving antihypertensive treatment experienced a greater increase in LAD with age (0.95 versus 0.63 mm per 10-year age increment) when compared with those not receiving antihypertensive treatment. Overall, greater risk factor burden was positively associated with LAD. These risk factors were also associated positively with 4-year change in LAD (P<0.001).Our longitudinal study of a large community-based sample identified higher BP and greater BMI as key modifiable correlates of LAD, suggesting that maintaining optimal levels of these risk factors through the life course may prevent atrial remodeling and AF.
Adenovirus mediated intra-articular expression of collagenase-3 (MMP-13) induces inflammatory arthritis in mice
Authors: K Joronen
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objectives:</b> To better understand the role of collagenase-3 (MMP-13) in joint inflammation by investigating the consequences of transient overexpression of human collagenase-3 (matrix metalloproteinase-13 (MMP-13)), introduced by adenoviral gene delivery, in the mouse knee joint. <b>Methods:</b> A single dose (5×10<sup>7</sup> pfu) of recombinant adenovirus coding either for β-galactosidase (RAdLacZ) or human MMP-13 (RAdMMP-13) was injected intra-articularly into the knee joint of adult mice. The joints were analysed at frequent intervals up to 4 weeks by histology, immunohistochemistry, and RNA analysis. <b>Results:</b> When RAdLacZ reporter virus was used, adenoviruses efficiently infected synovial cells, chondrocytes of articular cartilage, and hypertrophic chondrocytes of the growth plate. The infection was transient as no reporter gene activity was detected 3 weeks after the injection. After RAdMMP-13 injection into the knee joints, expression of human MMP-13 in joint tissues resulted in an arthritis characterised by recruitment of inflammatory cells and increased production of cytokines and chemokines, synovial hyperplasia, and pannus formation. After the loss of MMP-13 transgene expression at 3 weeks, these inflammatory changes began to diminish. <b>Conclusions:</b> MMP-13 has a role in the onset of inflammatory reaction in synovium. However, damage to articular cartilage was only rarely detected after the short term overexpression of MMP-13.
Expression of human lecithin-cholesterol acyltransferase in transgenic mice. Effect of human apolipoprotein AI and human apolipoprotein all on plasma lipoprotein cholesterol metabolism.
Authors: O L Francone, E L Gong, D S Ng, C J Fielding, E M Rubin
Journal: Journal of Clinical Investigation (1995)

Human (Hu) lecithin-cholesterol acyltransferase (LCAT) is a key enzyme in the plasma metabolism of cholesterol. To assess the effects of increased plasma levels of LCAT, four lines of transgenic mice were created expressing a Hu LCAT gene driven by either its natural or the mouse albumin enhancer promoter. Plasma LCAT activity increased from 1.2- to 1.6-fold higher than that found in control mouse plasma. Lipid profiles, upon comparing Hu LCAT transgenics to control animals, revealed a 20 t0 60% increase in total and cholesteryl esters that were mainly present in HDL. The in vivo substrate specificity of Hu LCAT was assessed by creating animals expressing Hu apo AI + Hu LCAT (HuAI/ LCAT), Hu apo AI + Hu apo AII + Hu LCAT (HuAI/ AII/LCAT), and Hu apo AII + Hu LCAT (HuAII/LCAT). Plasma cholesterol was increased up to 4.2-fold in HuAI/ LCAT transgenic mice and twofold in the HuAI/AII/LCAT transgenic mice, compared with HuAI and HuAI/AII transgenic mice. HDL cholesteryl ester levels were increased more than twofold in both the HuAI/LCAT and HuAI/AII/LCAT mice compared with the HuAI, HuAI/AII, and HuLCAT animals. The HDL particles were predominantly larger in the HuAI/LCAT and the HuAI/AII/LCAT mice compared with those in HuAI, HuAII/LCAT, and HuLCAT animals. The increase in LCAT activity in the HuAI/LCAT and HuAI/AII/LCAT mice was associated with 62 and 27% reductions respectively, in the proportion of Hu apo AI in the pre beta-HDL fraction, when compared with HuAI and HuAI/AII transgenic mice. These data demonstrate that moderate increases in LCAT activity are associated with significant changes in lipoprotein cholesterol levels and that Hu LCAT has a significant preference for HDL containing Hu apo AI.
Randomized Clinical Trial of Breast Irradiation Following Lumpectomy and Axillary Dissection for Node-Negative Breast Cancer: an Update
Authors: R. M. Clark, T. Whelan, M. Levine, R. Roberts, A. Willan, P. McCulloch, M. Lipa, R. H. Wilkinson, L. J. Mahoney
Journal: JNCI Journal of the National Cancer Institute (1996)

Background:Breast-conservation surgery is now commonly used to treat breast cancer. Postoperative breast irradiation reduces cancer recurrence in the breast. There is still controversy concerning the necessity of irradiation of the breast in all patients.
The effect of cord cleansing with chlorhexidine on neonatal mortality in rural Bangladesh: a community-based, cluster-randomised trial
Authors: Shams El Arifeen, Luke C Mullany, Rasheduzzaman Shah, Ishtiaq Mannan, Syed M Rahman, M Radwanur R Talukder, Nazma Begum, Ahmed Al-Kabir, Gary L Darmstadt, Mathuram Santosham, Robert E Black, Abdullah H Baqui
Journal: The Lancet (2012)
Baroreflex control of the circulation in chronically instrumented fetal lambs.
Authors: J Itskovitz, E F LaGamma, A M Rudolph
Journal: Circulation Research (1983)

The role of the arterial baroreceptors in regulating the fetal circulation was studied in 18 chronically instrumented fetal lambs, 120-136 days gestation. The results were compared to those obtained in three sinoaortic denervated adult sheep. Nine fetuses underwent sinoaortic denervation and nine fetuses served as sham-operated controls. Two to 3 days after surgery, heart rate and blood pressure were recorded continuously and analyzed over 1-hour periods. In the denervated fetuses, marked fluctuations of the arterial pressure and heart rate were observed. Frequency distribution curves for mean arterial pressure and heart rate showed broader and flatter curves in the denervated fetuses. The average mean arterial pressure and heart rate were not significantly different between the two groups. However, the standard deviation as an index of variability of the mean arterial pressure increased from 2.7 +/- 0.9 (mean +/- standard deviation) in the control group to 6.5 +/- 2.4 in the denervated fetuses, and the standard deviation of the heart rate increased from 10.6 +/- 2.1 to 21.5 +/- 5.7. In the adult sheep, mean arterial pressure and heart rate increased on the 1st day after denervation and returned to near control values on the 3rd day. The variability of the mean arterial pressure increased, but that of the heart rate did not change. Fetal cardiac output and its distribution were measured by the radionuclide-labeled microsphere technique. Combined ventricular output was not statistically different between the groups, but the blood flow to the fetal body was 27% higher in the denervated fetuses. The calculated fetal body vascular resistance was 31% lower in the denervated lambs. This study indicates that the arterial baroreceptors are important in regulating variability of the arterial pressure and heart rate in fetal life, and also may have a significant role in maintaining the normal peripheral vascular resistance.
Endothelin-1 Induces Cyclooxygenase-2 Expression Via Nuclear Factor of Activated T-Cell Transcription Factor in Glomerular Mesangial Cells
Authors: Toshiro Sugimoto, Masakazu Haneda, Hirotaka Sawano, Keiji Isshiki, Shiro Maeda, Daisuke Koya, Ken Inoki, Hitoshi Yasuda, Atsunori Kashiwagi, Ryuichi Kikkawa
Journal: Journal of the American Society of Nephrology (2001)

Nuclear factor of activated T cells (NFAT) originally was identified as a T-cell-specific transcription factor whose activity is regulated by calcineurin, one of the serine-threonine phosphatases. Recent studies have shown that NFAT also is expressed in nonlymphoid cells and plays an important role in various cell functions. It is widely known that treatment with cyclosporin A (CsA), which can inhibit calcineurin/NFAT signaling, results in glomerular dysfunction characterized by a decrease of GFR or glomerulosclerosis, suggesting that NFAT might regulate the glomerular function. However, the precise function of NFAT in glomerular cells remains to be clarified. Herein, evidence has been produced that NFAT2/NFATc, one of five known NFAT isoforms, is expressed in glomerular mesangial cells. Stimulation of mesangial cells with endothelin-1 caused translocation of NFAT2 into the nucleus with a concomitant increase in NFAT2 DNA-binding activity, both of which were inhibited by CsA. Furthermore, CsA inhibited endothelin-1-induced cyclooxygenase-2 (COX-2) expression in mesangial cells. NFAT2 bound directly to the GGAAA sequence, which is the minimal consensus sequence for NFAT binding, in a promoter region of rat COX-2 gene, and it enhanced the reporter activity of rat COX-2 promoter in mesangial cells. These findings provide the first evidence that NFAT2 is expressed and regulates COX-2 gene expression in mesangial cells. These results will contribute to evaluation of the precise roles of NFAT in glomerular functions and the CsA-induced nephrotoxicity.
Prevention of Gram-Negative Translocation Reduces the Severity of Hepatopulmonary Syndrome
Authors: Anne Rabiller, Hilario Nunes, Didier Lebrec, Khalid A. Tazi, Myriam Wartski, Elisabeth Dulmet, Jean-Marie Libert, Christine Mougeot, Richard Moreau, Michel Mazmanian, Marc Humbert, Philippe Hervé
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Hepatopulmonary syndrome (HPS) is characterized by intrapulmonary vascular dilatations and an increased alveoloarterial oxygen difference (AaPO(2)). These abnormalities are related to augmented pulmonary nitric oxide (NO) production, dependent primarily on increases in the expression and activity of inducible NO-synthase (iNOS) within pulmonary intravascular macrophages and, to a lesser extent, of endothelial NOS (eNOS). Production of iNOS by pulmonary intravascular macrophages might be related to translocated gut bacteria present in the pulmonary circulation. To test this hypothesis, we determined whether macrophage sequestration, lung iNOS expression and activity, and HPS severity were decreased after norfloxacin was given for 5 weeks to prevent Gram-negative bacterial translocation in rats with common bile duct ligation-induced cirrhosis. Norfloxacin decreased the incidence of Gram-negative translocation from 70 to 0% and the percentage of pulmonary microvessels containing more than 10 macrophages from 52 +/- 7 to 21 +/- 8% (p < 0.01). AaPO(2) and cerebral uptake of intravenous (99m)Tc-labeled albumin macroaggregates (reflecting intrapulmonary vascular dilatations) were intermediate to those of untreated cirrhotic and sham-operated rats. The activity and expression of lung iNOS, but not eNOS, were reduced to normal. Norfloxacin may reduce HPS severity by inhibiting Gram-negative bacterial translocation, thereby decreasing NO production by pulmonary intravascular macrophages. Bacterial translocation may be the key to the pathogenesis of HPS.
H2 antagonists in the treatment of reflux oesophagitis: can physiological studies predict the response?
Authors: D A Robertson, M A Aldersley, H Shepherd, R S Lloyd, C L Smith
Journal: Gut (1987)

Ambulatory oesophageal pH, oesophageal manometry and fasting serum gastrin concentrations were carried out on 28 patients with reflux oesophagitis, before and during treatment with ranitidine 300 mg bd. Fourteen patients healed endoscopically at six weeks (group A) and 14 had residual oesophagitis (group B). Group A were characterised by a lower serum gastrin concentration before treatment (4.52 pmol/l; 2.4-10: mean and range) than group B (11.1 pmol/l; 3.5-21: p less than 0.05) and showed a marked reduction in acid reflux on treatment to near normal values. Mean per cent time below pH4 fell from 14.9 to 4.2 in group A (p less than 0.05) but was not affected in group B (14.2-15.6, not significant). Abnormal oesophageal motility was found in 13 patients from each group. This did not inhibit the response to ranitidine, and was not improved by healing of oesophagitis.
Association of <i>CHFR</i> Promoter Methylation with Disease Recurrence in Locally Advanced Colon Cancer
Authors: Motofumi Tanaka, Ping Chang, Yanan Li, Donghui Li, Michael Overman, Dipen M. Maru, Salil Sethi, Jonathan Phillips, Gail L. Bland, James L. Abbruzzese, Cathy Eng
Journal: Clinical Cancer Research (2011)

This study was designed to determine whether DNA methylation biomarkers are associated with recurrence and survival in colon cancer patients.A retrospective analysis of 82 patients who received curative surgical resection for American Joint Committee on Cancer (AJCC) high-risk stage II or III colon cancer (1999-2007) was conducted. DNA methylation status was quantitatively evaluated by the pyrosequencing method. We preselected three tumor suppressor genes and one locus of interest; CHFR, ID4, RECK, and MINT1. Mean methylation levels of multiple CpG sites in the promoter regions were used for analysis; 15% or more was defined as methylation positive. The association of recurrence-free survival (RFS) and overall survival (OS) with methylation status was analyzed by the log-rank test, Kaplan-Meier method, and Cox proportional hazards model.Methylation levels of ID4, MINT1, and RECK did not correlate with RFS or OS. CHFR was methylation positive in 63% patients. When methylation status was dichotomized (negative or low: <30%, high: ≥30%), patients with CHFR methylation-high (44%) had worse RFS (P = 0.006) and reduced OS (P = 0.069). When stratified by stage, CHFR methylation-high was associated with reduced RFS (P = 0.004) and OS (P = 0.010) in stage III patients. CHFR methylation-high was commonly associated with N2 disease (P = 0.04) and proximal tumors (P = 0.002). Multivariate analysis indicated AJCC T4 disease and CHFR methylation-high (P = 0.001 and P = 0.015, respectively) were independent predictors for recurrence.The extent of CHFR promoter methylation correlates with RFS, indicating it is a promising epigenetic marker for recurrence.
Genomic and Proteomic Analysis Reveals a Threshold Level of MYC Required for Tumor Maintenance
Authors: Catherine M. Shachaf, Andrew J. Gentles, Sailaja Elchuri, Debashis Sahoo, Yoav Soen, Orr Sharpe, Omar D. Perez, Maria Chang, Dennis Mitchel, William H. Robinson, David Dill, Garry P. Nolan, Sylvia K. Plevritis, Dean W. Felsher
Journal: Cancer Research (2008)

Abstract MYC overexpression has been implicated in the pathogenesis of most types of human cancers. MYC is likely to contribute to tumorigenesis by its effects on global gene expression. Previously, we have shown that the loss of MYC overexpression is sufficient to reverse tumorigenesis. Here, we show that there is a precise threshold level of MYC expression required for maintaining the tumor phenotype, whereupon there is a switch from a gene expression program of proliferation to a state of proliferative arrest and apoptosis. Oligonucleotide microarray analysis and quantitative PCR were used to identify changes in expression in 3,921 genes, of which 2,348 were down-regulated and 1,573 were up-regulated. Critical changes in gene expression occurred at or near the MYC threshold, including genes implicated in the regulation of the G1-S and G2-M cell cycle checkpoints and death receptor/apoptosis signaling. Using two-dimensional protein analysis followed by mass spectrometry, phospho-flow fluorescence-activated cell sorting, and antibody arrays, we also identified changes at the protein level that contributed to MYC-dependent tumor regression. Proteins involved in mRNA translation decreased below threshold levels of MYC. Thus, at the MYC threshold, there is a loss of its ability to maintain tumorigenesis, with associated shifts in gene and protein expression that reestablish cell cycle checkpoints, halt protein translation, and promote apoptosis. [Cancer Res 2008;68(13):5132–42]
Splanchnic Metabolism of Plasma Apolipoprotein B
Authors: P. R. Turner, N. E. Miller, C. Cortese, W. Hazzard, J. Coltart, B. Lewis
Journal: Journal of Clinical Investigation (1981)

The metabolism of apoprotein B-containing plasma lipoproteins by human splanchnic tissues has been studied in 29 men undergoing coronary angiography. Before catheterization autologous radio-iodinated lipoproteins were infused into a peripheral vein: 10 subjects received 125I-labeled Sf 12-60 lipoproteins; 12 received 125I-labeled Sf 12-60 plus 131I-labeled Sf 100-400 lipoproteins; and 7 received 125I-labeled Sf 12-60 plus 131I-labeled Sf 0-12 lipoproteins. Paired arterial and hepatic vein blood samples were subsequently collected for replicate measurements of apoprotein B (apo B) mass, radioactivity and specific activity in each lipoprotein class. Splanchnic plasma flow was measured with indocyanine green. All studies were conducted after a 14-h overnight fast.
MPs question government's plan for a paperless NHS by 2018
Authors: A. O'Dowd
Journal: BMJ (2013)

Government plans for a “paperless” NHS by 2018 are unlikely to be achieved given the “fiasco” surrounding its handling of the National Programme for IT in the NHS, say MPs.

In a damning report published on 18 September, the parliamentary public accounts committee said that the national programme was one of the worst and most costly contracting fiascos in the history of the public sector.1

The report …
Cyclin K and cyclin D1b are oncogenic in myeloma cells
Authors: Véronique Marsaud, Guergana Tchakarska, Geoffroy Andrieux, Jian-Miao Liu, Doulaye Dembele, Bernard Jost, Joanna Wdzieczak-Bakala, Jack-Michel Renoir, Brigitte Sola
Journal: Molecular Cancer (2010)

Abstract Background Aberrant expression of cyclin D1 is a common feature in multiple myeloma (MM) and always associated with mantle cell lymphoma (MCL). CCND1 gene is alternatively spliced to produce two cyclin D1 mRNA isoforms which are translated in two proteins: cyclin D1a and cyclin D1b. Both isoforms are present in MM cell lines and primary cells but their relative role in the tumorigenic process is still elusive. Results To test the tumorigenic potential of cyclin D1b in vivo , we generated cell clones derived from the non- CCND1 expressing MM LP-1 cell line, synthesizing either cyclin D1b or cyclin K, a structural homolog and viral oncogenic form of cyclin D1a. Immunocompromised mice injected s.c . with LP-1K or LP-1D1b cells develop tumors at the site of injection. Genome-wide analysis of LP-1-derived cells indicated that several cellular processes were altered by cyclin D1b and/or cyclin K expression such as cell metabolism, signal transduction, regulation of transcription and translation. Importantly, cyclin K and cyclin D1b have no major action on cell cycle or apoptosis regulatory genes. Moreover, they impact differently cell functions. Cyclin K-expressing cells have lost their migration properties and display enhanced clonogenic capacities. Cyclin D1b promotes tumorigenesis through the stimulation of angiogenesis. Conclusions Our study indicates that cyclin D1b participates into MM pathogenesis via previously unrevealed actions.
Expression of the TRPV1 receptor differs in quiescent inflammatory bowel disease with or without abdominal pain
Authors: A. Akbar, Y. Yiangou, P. Facer, W. G. Brydon, J. R. F. Walters, P. Anand, S. Ghosh
Journal: Gut (2010)

<h3>Objective</h3> Transient receptor potential vanilloid type 1 (TRPV1) has been shown to play an important role in visceral hypersensitivity. A significant proportion of patients with inflammatory bowel disease (IBD) continue to complain of abdominal pain despite their disease being otherwise quiescent. We investigated TRPV1-immunoreactive fibres in rectosigmoid biopsies taken from such patients with correlation to abdominal pain severity. <h3>Methods</h3> Rectosigmoid biopsies were collected from 20 patients with quiescent IBD fulfilling Rome II criteria for irritable bowel syndrome (IBS), from 20 asymptomatic patients with quiescent IBD and from 28 controls. Abdominal pain scores were recorded using a validated questionnaire. TRPV1- and neuronal marker protein gene product 9.5 (PGP 9.5)-expressing nerve fibres, and lymphocytes (CD3 and CD4) were quantified, following immunohistochemistry with specific antibodies. The biopsy findings were related to abdominal pain scores. <h3>Results</h3> A significant 3.9-fold increase in median number of TRPV1-immunoreactive fibres was found in biopsies from patients with quiescent IBD with IBS symptoms when compared with controls (p&lt;0.0001) and a 5-fold increase when compared with the asymptomatic quiescent IBD group (p=0.0003). In the IBD with IBS symptoms group, the total nerve fibres (PGP 9.5) did not differ from those in the asymptomatic IBD group (p=0.10) or the control group (p=0.33) and neither did the CD3 lymphocyte (asymptomatic IBD group p=0.17; controls p=0.88) or CD4 lymphocyte (asymptomatic IBD group p=0.39; controls p=0.97) counts. In stepwise multivariate linear regression analysis, only TRPV1-immunoreactive nerve fibres (R<sup>2</sup>=0.8; p&lt;0.0001) were significantly related to the abdominal pain score. <h3>Conclusions</h3> Increased TRPV1 nerve fibres are seen in quiescent IBD with IBS-like symptoms together with a correlation to pain severity. TRPV1 may contribute to the pathophysiology of ongoing pain and visceral hypersensitivity in this group of patients, providing a potential therapeutic target.