tbuckley/cabot-search huggingface dataset:
Effects of Early Treatment With Statins on Short-term Clinical Outcomes in Acute Coronary Syndromes
Authors: Matthias Briel, Gregory G. Schwartz, Peter L. Thompson, James A. de Lemos, Michael A. Blazing, Gerrit-Anne van Es, Meral Kayikçioğlu, Hans-Richard Arntz, Frank R. den Hartog, Nic J. G. M. Veeger, Furio Colivicchi, Jocelyn Dupuis, Shinya Okazaki, R. Scott Wright, Heiner C. Bucher, Alain J. Nordmann
Journal: JAMA (2006)

The short-term effects of early treatment with statins in patients after the onset of acute coronary syndromes (ACS) for the outcomes of death, myocardial infarction (MI), and stroke are unclear.To evaluate relevant outcomes of patients from randomized controlled trials comparing early statin therapy with placebo or usual care at 1 and 4 months following ACS.Systematic search of electronic databases (MEDLINE, EMBASE, PASCAL, Cochrane Central Register) from their inception to August 2005, which was supplemented by contact with experts in the field. Two reviewers independently determined the eligibility of randomized controlled trials that compared treatment with statins with a control, were initiated within 14 days after onset of ACS, and had a minimal follow-up of 30 days. Trials with cerivastatin were only included in a sensitivity analysis.Information on baseline characteristics of included trials and patients, reported methodological quality, lipid levels, and clinical outcome was independently extracted by 2 investigators. Investigators from each included trial contributed additional data if necessary.Twelve trials involving 13 024 patients with ACS were included in the meta-analysis. The risk ratios for the combined end point of death, MI, and stroke for patients treated with early statin therapy compared with control therapy were 0.93 (95% confidence interval [CI], 0.80-1.09; P = .39) at 1 month and 0.93 (95% CI, 0.81-1.07; P = .30) at 4 months following ACS. There were no statistically significant risk reductions from statins for total death, total MI, total stroke, cardiovascular death, fatal or nonfatal MI, or revascularization procedures (percutaneous coronary intervention or coronary artery bypass graft surgery). Sensitivity analyses with restriction to trials of high quality or with additional data from a large trial using cerivastatin indicated summary risk ratios even closer to 1.Based on available evidence, initiation of statin therapy within 14 days following onset of ACS does not reduce death, MI, or stroke up to 4 months.
Generation of complement C3 and expression of cell membrane complement inhibitory proteins by human bronchial epithelium cell line
Authors: S. Varsano
Journal: Thorax (2000)

The interrelationship between human airway epithelium and complement proteins may affect airway defence, airway function, and airway epithelial integrity. A study was undertaken to determine (1) whether unstimulated human bronchial epithelium generates complement proteins and expresses cell membrane complement inhibitory proteins (CIP) and (2) whether stimulation by proinflammatory cytokines affects the generation of complement and expression of cell membrane CIP by these cells.Human bronchial epithelium cell line BEAS-2B was cultured in a serum-free medium. Cells were incubated with and without proinflammatory cytokines to assess unstimulated and stimulated generation of complement C3, C1q and C5 (by ELISA), and to examine the expression of cell membrane CIP decay accelerating factor (DAF; CD55), membrane cofactor protein (MCP; CD46), and CD59 (protectin) by flow cytometry analysis.Unstimulated human bronchial epithelial cell line BEAS-2B in serum-free medium generates complement C3 (mean 32 ng/10(6) cells/72 h, range 18-52) but not C1q and C5, and expresses cell membrane DAF, MCP, and CD59. Interleukin (IL)-1alpha (100 U/ml/72 h) and tumour necrosis factor (TNF-alpha; 1000 U/ml/72 h) increased generation of C3 up to a mean of 78% and 138%, respectively, above C3 generation by unstimulated cells. DAF was the only cell membrane CIP affected by cytokine stimulation. Interferon (IFN)-gamma (10 U/ml/72 h) and TNF-alpha (1000 U/ml/72 h) increased DAF expression up to a mean of 116% and 45%, respectively, above that in unstimulated cells. MCP and CD59 expression was not consistently affected by IL-1alpha, TNF-alpha, or IFN-gamma.Local generation of complement C3 and expression of cell membrane CIP by human bronchial epithelium and its modulation by proinflammatory cytokines might be an additional regulatory mechanism of local airway defence and may affect airway function and epithelial integrity in health and disease.
Cancer survival in Europe 1999–2007 by country and age: results of EUROCARE-5—a population-based study
Authors: Roberta De Angelis, Milena Sant, Michel P Coleman, Silvia Francisci, Paolo Baili, Daniela Pierannunzio, Annalisa Trama, Otto Visser, Hermann Brenner, Eva Ardanaz, Magdalena Bielska-Lasota, Gerda Engholm, Alice Nennecke, Sabine Siesling, Franco Berrino, Riccardo Capocaccia
Journal: The Lancet Oncology (2013)
The novel RASSF6 and RASSF10 candidate tumour suppressor genes are frequently epigenetically inactivated in childhood leukaemias
Authors: Luke B Hesson, Thomas L Dunwell, Wendy N Cooper, Daniel Catchpoole, Anna T Brini, Raffaella Chiaramonte, Mike Griffiths, Andrew D Chalmers, Eamonn R Maher, Farida Latif
Journal: Molecular Cancer (2009)

Abstract Background The Ras-assocation family (RASSF) of tumour suppressor genes (TSGs) contains 10 members that encode proteins containing Ras-assocation (RA) domains. Several members of the RASSF family are frequently epigenetically inactivated in cancer, however, their role in leukaemia has remained largely uninvestigated. Also, RASSF10 is a predicted gene yet to be experimentally verified. Here we cloned, characterised and demonstrated expression of RASSF10 in normal human bone marrow. We also determined the methylation status of CpG islands associated with RASSF1–10 in a series of childhood acute lymphocytic leukaemias (ALL) and normal blood and bone marrow samples. Results COBRA and bisulphite sequencing revealed RASSF6 and RASSF10 were the only RASSF members with a high frequency of leukaemia-specific methylation. RASSF6 was methylated in 94% (48/51) B-ALL and 41% (12/29) T-ALL, whilst RASSF10 was methylated in 16% (8/51) B-ALL and 88% (23/26) T-ALL. RASSF6 and RASSF10 expression inversely correlated with methylation which was restored by treatment with 5-aza-2'deoxycytidine (5azaDC). Conclusion This study shows the hypermethylation profile of RASSF genes in leukaemias is distinct from that of solid tumours and represents the first report of inactivation of RASSF6 or RASSF10 in cancer. These data show epigenetic inactivation of the candidate TSGs RASSF6 and RASSF10 is an extremely frequent event in the pathogenesis of childhood leukaemia. This study also warrants further investigation of the newly identified RASSF member RASSF10 and its potential role in leukaemia.
Identification of Gulf War Syndrome: Methodological Issues and Medical Illnesses
Authors: Victor Gordon
Journal: JAMA (1997)

<h3>To the Editor.</h3> —Despite its limitations, the study by Dr Haley and colleagues<sup>1</sup>is welcomed by clinicians like me who care for Persian Gulf War veterans. I would like to make several observations based on my experience gained from the evaluation and follow-up of 549 Gulf War veterans. Eighty-five percent of these veterans were younger than 30 years when first evaluated, most of them reside in the New England states, the majority of them are male, and they served in all military branches. Their self-reported symptoms fit well in the 6 syndromes described by Haley et al.<sup>1</sup>Even the words used by these veterans to describe their symptoms are strikingly similar to the terms used to describe the symptoms in this study. Many veterans in my group developed high intolerance to chemicals existing in the surrounding environment, experienced the onset of new allergies, including life-threatening reactions to bee
Reliability of commercially available immunocytochemical markers for identification of neuroendocrine differentiation in bronchoscopic biopsies of bronchial carcinoma.
Authors: J R Gosney, M A Gosney, M Lye, S A Butt
Journal: Thorax (1995)

BACKGROUND--Although neuroendocrine differentiation occurs quite commonly in non-small cell bronchial malignancies, its biological significance and implications for management remain uncertain. Determining these facts requires its recognition early, ideally at diagnosis, which is usually made on tissue from bronchoscopy, but the best means of its detection in such material is unclear. A prospective comparative study was performed of 10 commercially available antisera to a series of markers of neuroendocrine differentiation, to test their efficacy when applied to fibreoptic bronchoscopy biopsy specimens. METHODS--Expression of chromogranin A, synaptophysin, neurone-specific enolase, protein gene product 9.5, the BB isoenzyme of creatine kinase, gastrin releasing peptide, adrenocorticotrophic hormone, calcitonin, calcitonin gene related peptide, and leucine enkephalin was sought by immunolabelling of bronchoscopic biopsy tissue from 83 primary bronchial carcinomas, 22 of them of small cell type. RESULTS--Only synaptophysin and chromogranin were sensitive and specific enough for neuroendocrine differentiation to discriminate between small cell and non-small cell lesions, whereas protein gene product 9.5 and creatine kinase were neither particularly sensitive nor specific and neurone-specific enolase actually labelled more non-small cell tumours than small cell lesions. Of the five secretory products sought, only gastrin releasing peptide was detectable in just one tumour. Three squamous and two morphologically undifferentiated tumours immunolabelled for synaptophysin and chromogranin, almost certainly indicating neuroendocrine differentiation in the absence of small cell morphology. CONCLUSIONS--Of the markers studied, only synaptophysin and chromogranin were sufficiently specific and sensitive for neuroendocrine differentiation to justify their inclusion in any panel of antibodies used in its detection in tissue obtained at fibreoptic brochoscopy.
NOVEL APPROACH TO MODEL BRAIN TUMOURS BY INDUCING LOCALLY RESTRICTED AND STEM CELL SELECTIVE GENE TARGETING
Authors: S. Brandner, A. Benedykcinska, N. Li, N. Henriquez
Journal: Neuro-Oncology (2014)

BACKGROUND: A key challenge in determining the cellular origin of brain tumours is the identification and selective targeting of a biological relevant stem and progenitor population. Established approaches use cre mediated recombination of tumour suppressor genes, using constitutively expressed, inducible or topically administered cre expression. We have previously induced oligoastrocytomas by intraventricular injection of adenovirus expressing cre into mice carrying combinations of multiple floxed tumour suppressor genes (PTEN, p53, Rb) (1, 2). Here we set out to develop a targeted, temporally controlled approach to recombine specific subsets of progenitors in the stem cell compartment of the SVZ, whilst preventing widespread recombination of common inducible models (GFAP-Cre (ER(T), Nestin-Cre ER(T) and similar models (3)). METHODS: We developed a novel approach of gene recombination in a specific SVZ target cell. We used GLAST cre ER(T); PTENlox/lox;p53lox/lox mice, but instead of intraperitoneally injecting Tamoxifen, which leads to a widespread recombination of CNS astrocytes, and other cells (4) we injected the active compound 4OH-Tamoxifen directly into the ventricles. RESULTS: Direct intraventricular administration of 4OH-Tamoxifen into the cerebral ventricles of GLAST-CreER(T) mice successfully recombines tumour suppressor genes in GLAST expressing SVZ B-type stem cells. Recombination occurs proportionally to the 4OH-Tamoxifen dose. Resulting brain tumours, occurring at a frequency similar to that in Adeno-cre injected controls corresponded phenotypically to gliomas with a spectrum ranging from astrocytic to oligodendroglial tumours. CONCLUSIONS: We have developed a novel method to selectively recombine genetically defined cell populations, B-type SVZ stem cells, and have successfully elicited intrinsic brain tumours. Frequency and phenotypic spectrum of these tumours is similar to that induced by intraventricular adenovirus injections. The phenotype is also similar to those achieved by systemic tamoxifen injections, which achieve higher tumour frequencies (3) albeit using different promoters. We conclude that highly selective targeting of specific SVZ stem cell population is not essential to generate an effective model system for brain tumours. This conclusion has important implications for the development of biologically relevant brain tumour models. References: 1. N. V. Henriquez et al., Cancer Res, (Jul 25, 2013).2. T. S. Jacques et al., EMBO J 29, 222 (Jan 6, 2010).3. L. M. Chow et al., Cancer Cell 19, 305 (Mar 8, 2011).4. T. Mori et al., Glia 54, 21 (Jul, 2006). SECONDARY CATEGORY: Tumor Biology.
A randomized controlled trial of thymosin-?1 versus interferon alfa treatment in patients with hepatitis B e antigen antibody?and hepatitis B virus DNA?positive chronic hepatitis B
Authors: P Andreone, C Cursaro, A Gramenzi, C Zavaglia, I Rezakovic, E Altomare, R Severini, J S Franzone, O Albano, G Ideo, M Bernardi, G Gasbarrini
Journal: Hepatology (1996)

It has recently been shown that thymosin–α1(T–α1), a synthetic polypeptide of thymic origin, is able to promote disease remission and inhibition of hepatitis B virus (HBV) replication in patients affected by hepatitis B e antigen (HBeAg)–positive chronic active hepatitis. We evaluated the efficacy and safety of T–α1 treatment in patients with hepatitis B e antibody (anti–HBe) and HBV–DNA–positive chronic hepatitis. Thirty–three patients were randomly assigned to receive either T–α1 900 microg/m2 body surface area twice weekly (17 patients) or 5 MU of interferon alfa (IFN–α) three times weekly (16 patients) for 6 months. At baseline, both groups were comparable concerning age, sex, liver histology, and alanine transaminase (ALT) levels. At the end of treatment, complete response (defined as ALT normalization and HBV–DNA loss) occurred in 5 of 17 (29.4%) in the T–α1 group and in 7 of 16 (43.8%) in the IFN–α group ( P = not significant). After a follow–up period of 6 months, a complete response was observed in 7 of 17 (41.2%) in the T–α1 group and in 4 of 16 (25%) in the IFN–α group ( P = n.s.). Compared with the results observed in a group of 15 patients never treated with IFN–α and followed for 12 months, the rate of complete response was significantly higher in the IFN–α group at the end of therapy (1 of 15 vs. 7 of 16, respectively; P &lt; .05) and in the T–α1 group at the end of follow–up (1 of 15 vs. 7 of 17, respectively; P &lt; .05). Unlike IFN– α, T–α1 was well tolerated by all patients. The only side effect, reported by some, was local discomfort at injection sites. The results of this trial suggest that T–α1 is able to reduce HBV replication in patients affected by anti–HBe–positive chronic hepatitis. Furthermore, compared with IFN–α, T–α1 is better tolerated and seems to induce a gradual and more sustained ALT normalization and HBV–DNA loss. In conclusion, T–α1 appears to be a safe and effective alternative treatment for anti–HBe–positive chronic hepatitis. The benefit of this agent in producing long–term inhibition of HBV replication must be confirmed by future trials.
Year in review in Intensive Care Medicine, 2008: II. Experimental, acute respiratory failure and ARDS, mechanical ventilation and endotracheal intubation
Authors: Massimo Antonelli, Elie Azoulay, Marc Bonten, Jean Chastre, Giuseppe Citerio, Giorgio Conti, Daniel De Backer, François Lemaire, Herwig Gerlach, Johan Groeneveld, Goran Hedenstierna, Duncan Macrae, Jordi Mancebo, Salvatore M. Maggiore, Alexandre Mebazaa, Philipp Metnitz, Jerôme Pugin, Jan Wernerman, Haibo Zhang
Journal: Intensive Care Medicine (2009)

Also this year ICM published a number of interesting experimental articles, in large part focussed on mechanical ventilation, ARDS and sepsis. Mechanical ventilationVentilator-induced lung injury (VILI) is associated with inadequate inflammatory responses that lead to distal organ dysfunction.A variety of risk factors have been suggested to be involved in the pathogenesis of VILI in acute respiratory distress syndrome (ARDS), and it is noted that the mortality rate decreased in some younger but not other patients with ARDS.To test the hypothesis that aging increases the susceptibility to VILI and organ dysfunction, Dr. Esteban's group [1] conducted a study to mechanically ventilate young and old rats for an hour with a low or high tidal volume.They demonstrated that the high volume ventilatory strategy induced significantly greater systemic hypotension, cytokine production, distal organ dysfunction, and depressed vascular responses to catecholamines in the older than in the younger rats.The authors suggested that elderly subjects appear to be more prone to develop VILI and distal organ dysfunction compared to younger subjects.This interesting article was accompanied by an Editorial [2] to highlight the importance of the observation.Furthermore, the same group of investigators [3] demonstrated in the younger rats that the inflammatory responses and distal organ dysfunction induced by a short period (1 h) of high volume mechanical ventilation were reversible by 24-72 h in the surviving animals.This study suggests an important impact of the length of mechanical ventilation on the recovery of organ function, and multiple time points of a similar study are warranted.A number of studies have examined a variety of therapeutic approaches by improving ventilatory management or by using pharmacological intervention to reduce VILI in animal models.examined the effects of high-frequency percussive ventilation (HFPV), and compared it with high-frequency oscillatory ventilation (HFOV) and low volume ventilation on acute lung injury following gastric juice aspiration in rabbits.The HFPV was administered with a pneumatically powered volumetric diffusive respirator, which combines potential advantages of both high-frequency and convective ventilation.The investigators suggested that HFPV provided similar lung protective effects as did by HFOV and low volume ventilation, thus introduced an interesting therapeutic approach to attenuate VILI.It is noteworthy to mention that the neurally adjusted ventilatory assist (NAVA) has been shown to be protective in some experimental models of lung injury.NAVA utilizes
Calcium channel blockers prevent endothelial cell activation in response to necrotic trophoblast debris: possible relevance to pre-eclampsia
Authors: Q. Chen, F. Guo, S. Liu, J. Xiao, C. Wang, S. Snowise, P. R. Stone, L. W. Chamley
Journal: Cardiovascular Research (2012)

Pre-eclampsia is characterized by endothelial activation, which is triggered by placental factor(s). One such factor may be trophoblastic debris that is shed into the maternal blood to become trapped against the maternal pulmonary endothelium. Phagocytosis of necrotic trophoblastic debris (NTD) induces endothelial cell activation with increased secretion of interleukin-6 (IL-6) and transforming growth factor β1 (TGFβ1), which may induce systemic endothelial cell activation. In addition to its effects on vascular smooth muscle, evidence suggests that nifedipine may also affect the endothelium, contributing to the therapeutic benefits of the drug. We investigated whether nifedipine could reverse the endothelial cell activation induced by NTD.Trophoblastic debris was collected from placental explants and exposed to endothelial cells with or without nifedipine, verapamil, or a nitric oxide (NO) donor for 24 h. Endothelial cell activation was measured by cell-surface intracellular adhesion molecule-1 and E-selectin, as well as monocyte adhesion. The activation of endothelial cells exposed to NTD or sera from pre-eclamptic women was significantly reduced by nifedipine or verapamil. In addition, the increases in the levels of IL-6 or TGFβ1 in conditioned media from endothelial cells following phagocytosis of NTD were significantly reduced by nifedipine. These actions of nifedipine were reversed by the NO synthetase inhibitor l-NAME and mimicked by a NO donor.Our results suggest that calcium channel blockers may have a direct effect upon endothelial cells, reducing the endothelial cell activation that is a key pathogenic feature of pre-eclampsia. This action may be mediated, in part, by NO.
Re: 'Mitral valve prolapse in the dog: a model of mitral valve prolapse in man' (Cardiovasc Res 2000;47:234–243)
Authors: H Pedersen
Journal: Cardiovascular Research (2001)

We thank Dr. Cheng for his kind words about our review. In his letter, Dr. Cheng discusses the causes for sudden cardiac death associated with mitral valve prolapse (MVP), focussing on possible mechanisms for fatal ventricular arrhythmias, and invites us to come with comments.

As pointed out in our review, the incidence of sudden death in dogs with MVP is low. In our experience, both mild, clinically silent cases and more severe cases with marked regurgitation are affected, analogous …
Metallothionein expression in tattooed skin
Authors: None Hanada, None Hashimoto
Journal: British Journal of Dermatology (1998)

Journal Article Metallothionein expression in tattooed skin Get access K. Hanada, K. Hanada Department of Dermatology, Hirosaki University School of Medicine, Hirosaki 036, Japan Search for other works by this author on: Oxford Academic Google Scholar I. Hashimoto I. Hashimoto Department of Dermatology, Hirosaki University School of Medicine, Hirosaki 036, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 138, Issue 2, 1 February 1998, Pages 359–360, https://doi.org/10.1046/j.1365-2133.1998.02094.x Published: 01 February 1998
Does educational level influence lung function decline (Doetinchem Cohort Study)?
Authors: C. Tabak, A. M. W. Spijkerman, W. M. M. Verschuren, H. A. Smit
Journal: European Respiratory Journal (2009)

Low socioeconomic status is associated with reduced lung function in adults. In addition, there are indications that lung function decline with age is accelerated in low socioeconomic groups, but, to date, findings have been inconclusive. In order to investigate the relation between educational level, forced expiratory volume in 1 s (FEV1) and decline in FEV1 over time, linear mixed-effects models were fitted to baseline and 10-yr-follow-up data from the Doetinchem Cohort Study. The study population (26-66 yrs at baseline) consisted of 2,679 males and 3,026 females with an FEV1 measurement in at least one of the three rounds of follow-up and information on relevant covariables. High educational level was used as the reference class. Low educational level was associated with a higher prevalence of smoking and with a lower smoking-adjusted FEV1 at baseline (-148 mL in males and -47 mL in females). In females, low educational level was associated with a faster FEV1 decline (3.4 mL x yr(-1), age- and height-adjusted), which was not explained by smoking. In males, no differences in rates of decline between educational levels were observed. FEV1 decline was faster in less-educated females, independent of smoking. In males, FEV1 decline did not differ between educational levels.