tbuckley/cabot-search huggingface dataset:
Prognostic Value of the Modified American College of Cardiology/American Heart Association Stenosis Morphology Classification for Long-Term Angiographic and Clinical Outcome After Coronary Stent Placement
Authors: Adnan Kastrati, Albert Schömig, Shpend Elezi, Josef Dirschinger, Julinda Mehilli, Helmut Schühlen, Rudolf Blasini, Franz-Josef Neumann
Journal: Circulation (1999)

Background-The modified American College of Cardiology/American Heart Association (ACC/AHA) lesion morphology criteria are predictive of early outcome after various coronary catheter interventions. Their potential prognostic value after stent implantation and, in particular, for restenosis and long-term clinical outcome has not been studied. We assessed the prognostic value of the modified ACC/AHA criteria for the long-term angiographic and clinical outcome of patients after coronary stenting. Methods and Results-This study includes 2944 consecutive patients with symptomatic coronary artery disease treated with coronary stent placement. Modified ACC/AHA lesion morphology criteria were used to qualitatively assess the angiograms; type A and B1 lesions were categorized as simple, and type B2 and C lesions were designated complex. Primary end points were angiographic restenosis and 1-year event-free survival. Restenosis rate was 33.2% in complex lesions and 24.9% in simple lesions (P<0.001). It was 21. 7% for type A, 26.3% for type B1, 33.7% for type B2, and 32.6% for type C lesions. One-year event-free survival was 75.6% for patients with complex lesions and 81.1% for patients with simple lesions (P<0. 001). It was 85.2% for patients with type A, 79.4% for type B1, 75. 9% for type B2, and 75.2% type C lesions. The higher risk for restenosis and an adverse outcome associated with complex lesions was also maintained after multivariate adjustment for other clinical and angiographic characteristics. Conclusions-The modified ACC/AHA lesion morphology scheme has significant prognostic value for the outcome of patients after coronary stent placement. Lesion morphology is able to influence the restenosis process and thus the entire 1-year clinical course of these patients.
Nosocomial bloodstream infections due to Acinetobacter baumannii, Acinetobacter pittii and Acinetobacter nosocomialis in the United States
Authors: Hilmar Wisplinghoff, Tobias Paulus, Marianne Lugenheim, Danuta Stefanik, Paul G Higgins, Michael B Edmond, Richard P Wenzel, Harald Seifert
Journal: Journal of Infection (2011)
Evolution of C4 Phosphoenolpyruvate Carboxykinase in Grasses, from Genotype to Phenotype
Authors: Pascal-Antoine Christin, Blaise Petitpierre, Nicolas Salamin, Lucie Büchi, Guillaume Besnard
Journal: Molecular Biology and Evolution (2008)

C4 photosynthesis is an adaptation over the classical C3 pathway that has evolved multiple times independently. These convergences are accompanied by strong variations among the independent C4 lineages. The decarboxylating enzyme used to release CO2 around Rubisco particularly differs between C4 species, a criterion used to distinguish three distinct biochemical C4 subtypes. The phosphoenolpyruvate carboxykinase (PCK) serves as a primary decarboxylase in a minority of C4 species. This enzyme is also present in C3 plants, where it is responsible for nonphotosynthetic functions. The genetic changes responsible for the evolution of C4-specific PCK are still unidentified. Using phylogenetic analyses on PCK sequences isolated from C3 and C4 grasses, this study aimed at resolving the evolutionary history of C4-specific PCK enzymes. Four independent evolutions of C4-PCK were shown to be driven by positive selection, and nine C4-adaptive sites underwent parallel genetic changes in different C4 lineages. C4-adaptive residues were also observed in C4 species from the nicotinamide adenine dinucleotide phosphate–malic enzyme (NADP–ME) subtype and particularly in all taxa where a PCK shuttle was previously suggested to complement the NADP–ME pathway. Acquisitions of C4-specific PCKs were mapped on a species tree, which revealed that the PCK subtype probably appeared at the base of the Chloridoideae subfamily and was then recurrently lost and secondarily reacquired at least three times. Linking the genotype to subtype phenotype shed new lights on the evolutionary transitions between the different C4 subtypes.
AML engraftment in the NOD/SCID assay reflects the outcome of AML: implications for our understanding of the heterogeneity of AML
Authors: Daniel J. Pearce, David Taussig, Kazem Zibara, Lan-Lan Smith, Christopher M. Ridler, Claude Preudhomme, Bryan D. Young, Ama Z. Rohatiner, T. Andrew Lister, Dominique Bonnet
Journal: Blood (2005)
Sports utility vehicles and older pedestrians
Authors: Tony H Reinhardt-Rutland
Journal: BMJ (2005)

Editor—Recently, I commented on the paradox in attitudes to safety in private and public transport.1 I suggested that obvious, cheaply implemented safety improvements to private motoring—the example of banning the use of mobile telephones was under discussion—are often greeted with a chorus of protest that they impinge on the “freedom” of the motorist. In contrast, public transport is expected to spend vast sums of money to improve safety, even if the improvement is likely to be marginal. I cited the example of the replacement of “slam door” rolling stock on Britain's railways, which casualty records show will have a minimal effect.​effect.
Idiotypic determinants on T-cell subpopulations.
Authors: H Binz, H Frischknecht, F W Shen, H Wigzell
Journal: The Journal of Experimental Medicine (1979)

Killer T cells with specificity for major histocompatibility antigens have been shown in mice and rats to display idiotypic receptors allowing the lysis of such cells at the effector phase by anti-idiotypic antibodies and complement. A comparison was made between idiotypes displayed by Lyt-1-2+3+ and Lyt-1+2-3- T blasts, generated in the same mixed leucocyte culture (MLC), across an entire H-2 locus barrier. This was done by absorption of anti-idiotypic antibodies with respective T blasts, followed by estimation of the ability of the absorbed antiserum to inhibit MLC or killer T-cell function. Further, the capacity of Lyt-purified, MLC-generated T blasts to provoke specific unresponsiveness via anti-idiotypic immunity in syngeneic recipients was analyzed. Taken together, the results demonstrate that Lyt-1+2-3- T blasts responsible for the major part of MLC proliferation have distincly different idiotypes from those on the Lyt 1-2+3+ killer T cells. That the idiotypes on the killer T-cell presursors can serve as triggering sites for induction of effector T-cell function was then suggested by experiments with Lyt-1-2+3+-purified, normal T cells as precursor cells in vitro. The fact that autoanti-idiotypic antibodies may circumvent the need for helper Lyt-1+2-3- T cells in the generation of allospecific killer T cells indicates that the former cells may normally function partly via such anti-idiotypic reactions.
Brain lesions in septic shock: a magnetic resonance imaging study
Authors: Tarek Sharshar, Robert Carlier, Francis Bernard, Céline Guidoux, Jean-Philippe Brouland, Olivier Nardi, Geoffroy Lorin de la Grandmaison, Jérôme Aboab, Françoise Gray, David Menon, Djillali Annane
Journal: Intensive Care Medicine (2007)
Maintenance Therapy with Unprocessed Bran in the Prevention of Acute Anal Fissure Recurrence
Authors: S L Jensen
Journal: Journal of the Royal Society of Medicine (1987)

The effect of unprocessed bran in a dose of 5 g three times daily and a dose of 2.5 g three times daily for one year on the recurrence rate of anal fissures was studied in a double-blind, placebo-controlled trial in 90 patients with recently healed acute posterior anal fissures. Fifteen patients (16.6%) were withdrawn before the code was broken due to failure to follow the trial protocol for various reasons. Significantly fewer recurrences occurred in patients receiving bran 5 g throe times daily (recurrence rate 16%, 95% confidence limits, 4.54 to 36.08) when compared with patients receiving bran 2.5 g three times daily (60%; 38.67 to 78.87) ( P&lt;0.01) and with patients receiving placebo three times daily (68%; 46.50 to 85.05) ( P&lt;0.01). No significant difference in recurrences was found between patients on bran 2.5 g and those on placebo.
Regulation of the human oxytocin receptor in the uterus: a molecular approach
Authors: T Kimura
Journal: Human Reproduction Update (1998)

The oxytocin-oxytocin receptor (OTR) system plays important roles in the human uterus, and the effectiveness of oxytocin is greatly influenced by the pattern of receptor expression in vivo. To investigate OTR expression at the molecular level, we have established a bioassay system for the specific transcripts using Xenopus laevis oocytes, cloned the OTR cDNA, raised anti-OTR antibodies, and characterized OTR genomic clones and systems to study the transcriptional regulation of the gene. Using these molecular tools, we have examined OTR expression in the endometrium and myometrium of non-pregnant and pregnant women. OTR expression appears mainly to be regulated at the transcription level. Analysis of the 5' flanking region of this gene indicates constitutionally active promoter activity when transfected into cultured HeLa and SKN cells. We are currently developing these techniques to analyse OTR regulation in the uterus.
Immunofluorescent tracing of cytoplasmic components involved in keratinocyte differentiation
Authors: J. H. SAURAT, L. DIDIERJEAN, F. BEUCHER, E. GLUCKMAN
Journal: British Journal of Dermatology (1978)

Journal Article Immunofluorescent tracing of cytoplasmic components involved in keratinocyte differentiation Get access J. H. SAURAT, J. H. SAURAT Clinique Dermatologique Hôspital Saint‐Louis, 2 Place Alfred Fournier, 75475 Paris cedex 10, France etLaboratoire de Pathologie Experimentale, C.H.U. Necker‐Enfants Malades, 156 rue de Vaugirard, 75730 Paris cedex 15, France Search for other works by this author on: Oxford Academic Google Scholar L. DIDIERJEAN, L. DIDIERJEAN Clinique Dermatologique Hôspital Saint‐Louis, 2 Place Alfred Fournier, 75475 Paris cedex 10, France et Search for other works by this author on: Oxford Academic Google Scholar F. BEUCHER, F. BEUCHER Laboratoire de Pathologie Experimentale, C.H.U. Necker‐Enfants Malades, 156 rue de Vaugirard, 75730 Paris cedex 15, France Search for other works by this author on: Oxford Academic Google Scholar E. GLUCKMAN E. GLUCKMAN Clinique des maladies du sang, Hôspital Saint‐Louis, 2 Place Alfred Fournier, 75475 Paris cedex 10, France et Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 98, Issue 2, 1 February 1978, Pages 155–163, https://doi.org/10.1111/j.1365-2133.1978.tb01617.x Published: 01 February 1978
Fasting Compared With Nonfasting Triglycerides and Risk of Cardiovascular Events in Women
Authors: Sandeep Bansal, Julie E. Buring, Nader Rifai, Samia Mora, Frank M. Sacks, Paul M Ridker
Journal: JAMA (2007)

The association of triglycerides with incident cardiovascular disease remains controversial. Although triglyceride levels are typically obtained in the fasting state, postprandial hypertriglyceridemia may play an important role in atherosclerosis.To determine the association of triglyceride levels (fasting vs nonfasting) and risk of future cardiovascular events.Prospective study of 26,509 initially healthy US women (20,118 fasting and 6391 nonfasting) participating in the Women's Health Study, enrolled between November 1992 and July 1995 and undergoing follow-up for a median of 11.4 years. Triglyceride levels were measured in blood samples obtained at time of enrollment.Hazard ratios for incident cardiovascular events (nonfatal myocardial infarction, nonfatal ischemic stroke, coronary revascularization, or cardiovascular death).At baseline, triglyceride levels in fasting as well as nonfasting women correlated with traditional cardiac risk factors and markers of insulin resistance. During a median follow-up of 11.4 years, 1001 participants experienced an incident cardiovascular event (including 276 nonfatal myocardial infarctions, 265 ischemic strokes, 628 coronary revascularizations, and 163 cardiovascular deaths), for an overall rate of 3.46 cardiovascular events per 1000 person-years of follow-up. After adjusting for age, blood pressure, smoking, and use of hormone therapy, both fasting and nonfasting triglyceride levels predicted cardiovascular events. Among fasting participants, further adjustment for levels of total and high-density lipoprotein cholesterol and measures of insulin resistance weakened this association (fully adjusted hazard ratio [95% confidence interval] for increasing tertiles of triglyceride levels: 1 [reference], 1.21 [0.96-1.52], and 1.09 [0.85-1.41] [P = .90 for trend]). In contrast, nonfasting triglyceride levels maintained a strong independent relationship with cardiovascular events in fully adjusted models (hazard ratio [95% confidence interval] for increasing tertiles of levels: 1 [reference], 1.44 [0.90-2.29], and 1.98 [1.21-3.25] [P = .006 for trend]). In secondary analyses stratified by time since participants' last meal, triglyceride levels measured 2 to 4 hours postprandially had the strongest association with cardiovascular events (fully adjusted hazard ratio [95% confidence interval] for highest vs lowest tertiles of levels, 4.48 [1.98-10.15] [P<.001 for trend]), and this association progressively decreased with longer periods of fasting.In this cohort of initially healthy women, nonfasting triglyceride levels were associated with incident cardiovascular events, independent of traditional cardiac risk factors, levels of other lipids, and markers of insulin resistance; by contrast, fasting triglyceride levels showed little independent relationship.
PMO-119 Phenotypically and functionally distinct monocyte subsets and their role in human liver disease
Authors: E Liaskou, H Zimmermann, Z Stamataki, O Qureshi, S S Choi, J Shaw, S M Curbishley, W K Syn, D H Adams
Journal: Gut (2012)

<h3>Introduction</h3> Chronic liver inflammation is a leading cause of morbidity and mortality world wide, characterised by a dysregulated tissue repair driven by uncontrolled inflammation that leads to fibrosis, cirrhosis and hepatocellular carcinoma. We have investigated the role of different monocyte subsets: classical (CD14++CD16−/Mon1), intermediate (CD14++CD16+/Mon2) and non-classical (CD14+CD16++/Mon3) monocytes in human liver disease. <h3>Methods</h3> Liver-infiltrating and peripheral blood mononuclear cells (MNC) were isolated from normal individuals or patients with liver disease (ALD/NASH/PSC/AIH) and sorted into phenotypic subsets that were studied for their differentiation in response to Th1/Th2 cytokines by flow cytometry, migration across TNFα/IFNγ stimulated hepatic sinusoidal endothelial cells (HSEC) under physiological flow and phagocytic activity of zymosan bioparticles. The ability of different monocytes to activate hepatic stellate cells (HSC) was assessed using QRT-PCR (aSMA and COL1α1 gene expression changes). In this study monocyte subsets are defined as Mon1 (CD14++CD16−), Mon2 (CD14++CD16++) and Mon3 (CD14+CD16++). In functional experiments Mon2 and Mon3 were studied together and are defined as total CD16+ monocytes. <h3>Results</h3> Mon1 comprised 80% of MNC in the blood of healthy subjects and patients with liver disease but only 50% of MNC in both normal and diseased liver. Mon2 comprised 9% and 14% of MNC in normal and diseased blood respectively, but were significantly increased in normal and diseased livers (42 and 30% of MNC, respectively). Transmigration of total CD16+ monocytes across inflamed HSEC was 2.3-fold higher compared to CD14+ respectively. In vitro stimulation of Mon1 with TGFβ1 or IL-10 for 5 days induced 16- and 20-fold increases in CD16 expression. Liver infiltrating Mon2 expressed higher levels of CD163 and HLA-DR compared to Mon1, colocalized with CD68 and demonstrated high phagocytic activity, indicative of a macrophage phenotype. Diseased-liver-derived total CD16+ monocytes secreted higher levels of CCL2, IL-6, IL-8 and IL-13 and induced a twofold increase in aSMA and COL1a1 expression in co-cultured HSC. <h3>Conclusion</h3> Compared with normal livers, diseased livers harbour fewer CD14+ but significantly more CD16+ monocytes that secrete profibrotic cytokines and are able to activate HSC. CD16+ monocyte accumulation in the liver is the result of enhanced recruitment from blood and also local differentiation from CD14+ in response to TGFβ1 and IL-10 present in the fibrotic microenvironment. <h3>Competing interests</h3> None declared.
RB-Pathway Disruption Is Associated with Improved Response to Neoadjuvant Chemotherapy in Breast Cancer
Authors: Agnieszka K. Witkiewicz, Adam Ertel, Jeanne McFalls, Matias E. Valsecchi, Gordon Schwartz, Erik S. Knudsen
Journal: Clinical Cancer Research (2012)

Abstract Purpose: We sought to determine whether dysregulation of the retinoblastoma (RB) tumor suppressor pathway was associated with improved response to neoadjuvant chemotherapy in breast cancer. Experimental Design: An RB-loss signature was used to analyze the association between pathway status and pathologic complete response in gene expression datasets encompassing three different neoadjuvant regimens. Parallel immunohistochemical analysis of the RB pathway was conducted on pretreatment biopsies to determine the association with pathologic response to neoadjuvant chemotherapy. Results: An RB-loss gene expression signature was associated with increased pathologic complete response in datasets from breast cancer patients treated with 5-fluorouracil/adriamycin/cytoxan (FAC; P &amp;lt; 0.001), T/FAC (P &amp;lt; 0.001), and Taxane/Adriaymcin (P &amp;lt; 0.001) neoadjuvant therapy encompassing approximately 1,000 patients. The association with improved response to neoadjuvant chemotherapy was true in both estrogen receptor (ER)–positive and ER-negative breast cancer. Elevated expression of p16ink4a is associated with the RB-loss signature (R = 0.493–0.5982), and correspondingly p16ink4a mRNA levels were strongly associated with pathologic complete response in the same datasets analyzed. In an independent cohort, immunohistochemical analyses of RB and p16ink4a revealed an association of RB loss (P = 0.0018) or elevated p16ink4a (P = 0.0253) with pathologic complete response. In addition, by Miller–Payne and clinicopathologic scoring analyses, RB-deficient tumors experienced an overall improved response to neoadjuvant chemotherapy. Conclusion: Disruption of the RB pathway as measured by several independent methods was associated with improved response to neoadjuvant chemotherapy. The RB-pathway status was relevant for pathologic response in both ER-positive and ER-negative breast cancer with similar results observed with multiple chemotherapy regimens. Combined, these data indicate that RB status is associated with the response to neoadjuvant chemotherapy in breast cancer and could be used to inform treatment. Clin Cancer Res; 18(18); 5110–22. ©2012 AACR.
Cofactor of BRCA1: A Novel Transcription Factor Regulator in Upper Gastrointestinal Adenocarcinomas
Authors: Patricia A. McChesney, Sarah E. Aiyar, Ok-Jae Lee, Alexander Zaika, Christopher Moskaluk, Rong Li, Wa'el El-Rifai
Journal: Cancer Research (2006)

Abstract Cofactor of BRCA1 (COBRA1) is a newly characterized member of the negative elongation factor (NELF) complex. In this work, we show that COBRA1 is overexpressed in the majority of primary upper gastrointestinal adenocarcinomas (UGC), and its overexpression correlates with down-regulation of TFF1. We have detected overexpression of COBRA1 mRNA using quantitative real-time reverse transcription-PCR in 28 (79%) primary UGCs. Immunohistochemical analysis of UGC tissue arrays that contained 70 tumor samples showed moderate-strong staining for COBRA1 in 60 (84%) tumors. Interestingly, the tumor samples showed absent-weak staining for TFF1 in 45 (65%) of the tumors. Simultaneous loss of TFF1 expression and overexpression of COBRA1 was observed in 42 of 70 (60%) tumors. Using small interfering RNA technology with gastric cancer cells, we have shown that COBRA1 inhibition leads to increased TFF1 promoter activity and gene expression. Promoter analysis of TFF1 indicated that regulation of TFF1 by COBRA1 is estrogen independent in contrast to breast cancer. Moreover, COBRA1 regulation of TFF1 in gastric cancer cells was independent of NELF-E. Using several truncated mutants and site mutants of the TFF1 promoter, we have shown that COBRA1 can negatively regulate the activator protein-1 (AP-1) complex at the TFF1 promoter and thus down-regulate TFF1 expression in gastric cancer cell lines. Electrophoretic mobility shift assay showed that COBRA1 attenuates AP-1 binding to DNA. Our results suggest COBRA1 as a novel oncogene in UGCs that regulate AP-1 binding and the expression of TFF1 in upper gastric epithelia. (Cancer Res 2006; 66(3): 1346-53)
Prevalence and severity of self-reported asthma in young adults, 1976-2004
Authors: A. Browatzki, C. S. Ulrik, P. Lange
Journal: European Respiratory Journal (2009)

The aim of the present study was to describe the prevalence and severity of asthma in young Danish adults over three decades. Males and females aged 20-35 yrs were sampled from the population of Copenhagen for the three surveys (1976-1978, 1991-1993 and 2001-2004). A total of 3,285 (46% male) subjects answered a questionnaire, and had their height, weight, forced expiratory volume in 1 s (FEV1) and forced vital capacity measured. The prevalence of self-reported asthma was 1.5, 4.7 and 6.9%, respectively, in the three surveys (p<0.001). An increasing prevalence of asthma was observed in both males and females, although it was highest among females. The difference in FEV1 between asthmatic and nonasthmatic subjects gradually increased, being 2.3 (p = 0.56) and 14.2% of the predicted value (p<0.001), respectively, in 1976-1978 and 2001-2004. From the 1991-1994 survey, increasing body mass index, especially >30 kg.m(-2), was associated with a lower percentage predicted FEV1 (p< or =0.005), and further analyses suggested an additive effect of asthma and obesity on FEV1. The proportion of smokers declined from 60 to 38% (p<0.001). The prevalence and severity of asthma have continued to increase over the last three decades among young Danish adults, and the observed increase in severity seems, at least partly, to be related to the increase in prevalence of obesity.
Computational discovery of regulatory elements in a continuous expression space
Authors: Mathieu Lajoie, Olivier Gascuel, Vincent Lefort, Laurent Bréhélin
Journal: Genome biology (2012)

Approaches for regulatory element discovery from gene expression data usually rely on clustering algorithms to partition the data into clusters of co-expressed genes. Gene regulatory sequences are then mined to find overrepresented motifs in each cluster. However, this ad hoc partition rarely fits the biological reality. We propose a novel method called RED2 that avoids data clustering by estimating motif densities locally around each gene. We show that RED2 detects numerous motifs not detected by clustering-based approaches, and that most of these correspond to characterized motifs. RED2 can be accessed online through a user-friendly interface.