tbuckley/cabot-search huggingface dataset:
The proteome of Toxoplasma gondii: integration with the genome provides novel insights into gene expression and annotation
Authors: Dong Xia, Sanya J Sanderson, Andrew R Jones, Judith H Prieto, John R Yates, Elizabeth Bromley, Fiona M Tomley, Kalpana Lal, Robert E Sinden, Brian P Brunk, David S Roos, Jonathan M Wastling
Journal: Genome biology (2008)

Although the genomes of many of the most important human and animal pathogens have now been sequenced, our understanding of the actual proteins expressed by these genomes and how well they predict protein sequence and expression is still deficient. We have used three complementary approaches (two-dimensional electrophoresis, gel-liquid chromatography linked tandem mass spectrometry and MudPIT) to analyze the proteome of Toxoplasma gondii, a parasite of medical and veterinary significance, and have developed a public repository for these data within ToxoDB, making for the first time proteomics data an integral part of this key genome resource. The draft genome for Toxoplasma predicts around 8,000 genes with varying degrees of confidence. Our data demonstrate how proteomics can inform these predictions and help discover new genes. We have identified nearly one-third (2,252) of all the predicted proteins, with 2,477 intron-spanning peptides providing supporting evidence for correct splice site annotation. Functional predictions for each protein and key pathways were determined from the proteome. Importantly, we show evidence for many proteins that match alternative gene models, or previously unpredicted genes. For example, approximately 15% of peptides matched more convincingly to alternative gene models. We also compared our data with existing transcriptional data in which we highlight apparent discrepancies between gene transcription and protein expression. Our data demonstrate the importance of protein data in expression profiling experiments and highlight the necessity of integrating proteomic with genomic data so that iterative refinements of both annotation and expression models are possible.
In triple negative breast tumor cells, PLC-β2 promotes the conversion of CD133high to CD133low phenotype and reduces the CD133-related invasiveness
Authors: Federica Brugnoli, Silvia Grassilli, Manuela Piazzi, Maria Palomba, Ervin Nika, Alberto Bavelloni, Silvano Capitani, Valeria Bertagnolo
Journal: Molecular Cancer (2013)

Abstract Background Beyond its possible correlation with stemness of tumor cells, CD133/prominin1 is considered an important marker in breast cancer, since it correlates with tumor size, metastasis and clinical stage of triple-negative breast cancers (TNBC), to date the highest risk breast neoplasia. Methods To study the correlation between the levels of CD133 expression and the biology of breast-derived cells, CD133 low and CD133 high cell subpopulations isolated from triple negative MDA-MB-231 cells were compared in terms of malignant properties and protein expression. Results High expression of CD133 characterizes cells with larger adhesion area, lower proliferation rate and reduced migration speed, indicative of a less undifferentiated phenotype. Conversely, when compared with CD133 low cells, CD133 high cells show higher invasive capability and increased expression of proteins involved in metastasis and drug-resistance of breast tumors. Among the signalling proteins examined, PLC-β2 expression inversely correlates with the levels of CD133 and has a role in inducing the CD133 high cells to CD133 low cells conversion, suggesting that, in TNBC cells, the de-regulation of this PLC isoform is responsible of the switch from an early to a mature tumoral phenotype also by reducing the expression of CD133. Conclusions Since CD133 plays a role in determining the invasiveness of CD133 high cells, it may constitute an attractive target to reduce the metastatic potential of TNBC. In addition, our data showing that the forced up-regulation of PLC-β2 counteracts the invasiveness of CD133-positive MDA-MB-231 cells might contribute to identify unexplored key steps responsible for the TNBC high malignancy, to be considered for potential therapeutic strategies.
Characterization of a malignant T-cell line established from a rare case of CD8<sup>+</sup>CD56<sup>+</sup>Sézary syndrome
Authors: T. Shimauchi, H. Yagi, K. Sasada, Y. Kito, T. Ito, S. Hirakawa, Y. Tokura
Journal: British Journal of Dermatology (2012)

Journal Article Characterization of a malignant T‐cell line established from a rare case of CD8+CD56+ Sézary syndrome Get access T. Shimauchi, T. Shimauchi Department of Dermatology, Hamamatsu University School of Medicine, 1‐20‐1, Handayama, Higashi‐ku, Hamamatsu 431‐3192, Japan Search for other works by this author on: Oxford Academic Google Scholar H. Yagi, H. Yagi Department of Dermatology, Hamamatsu University School of Medicine, 1‐20‐1, Handayama, Higashi‐ku, Hamamatsu 431‐3192, Japan Search for other works by this author on: Oxford Academic Google Scholar K. Sasada, K. Sasada Department of Dermatology, Hamamatsu University School of Medicine, 1‐20‐1, Handayama, Higashi‐ku, Hamamatsu 431‐3192, Japan Search for other works by this author on: Oxford Academic Google Scholar Y. Kito, Y. Kito Department of Dermatology, Hamamatsu University School of Medicine, 1‐20‐1, Handayama, Higashi‐ku, Hamamatsu 431‐3192, Japan Search for other works by this author on: Oxford Academic Google Scholar T. Ito, T. Ito Department of Dermatology, Hamamatsu University School of Medicine, 1‐20‐1, Handayama, Higashi‐ku, Hamamatsu 431‐3192, Japan Search for other works by this author on: Oxford Academic Google Scholar S. Hirakawa, S. Hirakawa Department of Dermatology, Hamamatsu University School of Medicine, 1‐20‐1, Handayama, Higashi‐ku, Hamamatsu 431‐3192, Japan Search for other works by this author on: Oxford Academic Google Scholar Y. Tokura Y. Tokura Department of Dermatology, Hamamatsu University School of Medicine, 1‐20‐1, Handayama, Higashi‐ku, Hamamatsu 431‐3192, Japan Yoshiki Tokura. E‐mail: tokura@hama-med.ac.jp Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 168, Issue 4, 1 April 2013, Pages 885–887, https://doi.org/10.1111/bjd.12058 Published: 01 April 2013
Impact of Fluoroscopically-Visible Fluttering Flap on Clinical Diagnosis of Acute Aortic Dissection
Authors: Yoshihiro Tanaka, Kenji Sakata, Masa-aki Kawashiri, Chiaki Nakanishi, Tetsuo Konno, Tsuyoshi Yoshimuta, Kenshi Hayashi, Shigeyuki Tomita, Go Watanabe, Masakazu Yamagishi
Journal: Journal of the American College of Cardiology (2014)
Feasibility of Combined Percutaneous Transluminal Angioplasty and Minimally Invasive Direct Coronary Artery Bypass in Patients With Multivessel Coronary Artery Disease
Authors: Howard A. Cohen, Marco Zenati, A.J. Conrad Smith, Joon S. Lee, Simon Chough, Zubair Jafar, Peter Counihan, Mark Izzo, J.E. Burchenal, Arthur M. Feldman, Bartley Griffith
Journal: Circulation (1998)

Background —Angioplasty has become an accepted treatment of patients with coronary artery disease and is now commonly used to treat patients with multivessel disease. The major disadvantage of angioplasty has been restenosis requiring repeat interventions with resultant loss of initial cost savings. Compared with the right and the circumflex coronary arteries, the left anterior descending artery (LAD) has been more adversely affected by restenosis. Recently, minimally invasive direct coronary artery bypass (MIDCAB) to the LAD through a small left anterior thoracotomy using the left internal mammary artery has been performed in some centers with excellent early results and with reduced costs compared with standard bypass surgery. Methods and Results —We retrospectively reviewed the first 31 consecutive patients treated in our institution with integrated coronary revascularization (ICR): MIDCAB to the LAD combined with PTCA of the other diseased vessels in patients with multivessel disease. Postoperative angiography in 84% of patients revealed a patent anastomosis and normal flow in the graft and bypassed vessel. Thirty-eight (97%) of 39 vessels were successfully treated percutaneously. At a mean follow-up of 7 months, all patients are currently asymptomatic. There have been 2 adverse clinical events, both related to angioplasty and not to MIDCAB. The average length of stay at the hospital after MIDCAB was 2.79±1.05 days. Conclusions —These preliminary results with ICR are encouraging and suggest that a randomized, prospective clinical trial comparing ICR with standard coronary artery bypass surgery for the revascularization of symptomatic patients with multivessel disease involving the LAD is warranted.
miR-27a regulates cisplatin resistance and metastasis by targeting RKIP in human lung adenocarcinoma cells
Authors: Jipeng Li, Yiping Wang, Yulan Song, Zhongming Fu, Wanjun Yu
Journal: Molecular Cancer (2014)

MicroRNAs (miRNAs) have been identified as important posttranscriptional regulators involved in various biological and pathological processes of cells, but their association with tumor chemoresistance has not been fully understood. We detected miR-27a expression in two lung adenocarcinoma cell lines, A549 and A549/CDDP, and then investigated the effects of miR-27a on the metastasis and the chemosensitivity of cancer cells, using both gain- and loss-of-function studies. The correlation between miR-27a level and chemoresistance was further investigated in clinical lung adenocarcinoma specimens. miR-27a was significantly up-regulated in cisplatin-resistant lung adenocarcinoma A549/CDDP cells compared with parental A549 cells. miR-27a regulates epithelial-mesenchymal transition (EMT) and cisplatin resistance in vitro and modulates response of lung adenocarcinoma cells to cisplatin in vivo. Further studies identified Raf Kinase Inhibitory Protein (RKIP) as a direct and functional target of miR-27a. Small interfering RNA-mediated RKIP knockdown revealed similar effects as that of ectopic miR-27a expression, while overexpression of RKIP attenuated the function of miR-27a in lung adenocarcinoma cells. Increased miR-27a expression was also detected in tumor tissues sampled from lung adenocarcinoma patients treated with cisplatin-based chemotherapy and was proved to be correlated with low expression of RKIP, decreased sensitivity to cisplatin, and poor prognosis. Our results suggest that up-regulation of miR-27a could suppress RKIP expression and in turn contribute to chemoresistance of lung adenocarcinoma cells to cisplatin.
Diagnostic Performance of Soluble Mesothelin and Megakaryocyte Potentiating Factor in Mesothelioma
Authors: Kevin Hollevoet, Kristiaan Nackaerts, Joël Thimpont, Paul Germonpré, Lionel Bosquée, Paul De Vuyst, Catherine Legrand, Eliane Kellen, Yoshiro Kishi, Joris R. Delanghe, Jan P. van Meerbeeck
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Soluble mesothelin (SM) is currently the reference serum biomarker of malignant pleural mesothelioma (MPM). Megakaryocyte potentiating factor (MPF), which originates from the same precursor protein, is potentially more sensitive, yet lacks validation.To analyze the diagnostic performance of MPF as an MPM biomarker and compare this performance with SM.A total of 507 participants were enrolled in six cohorts: healthy control subjects (n = 101), healthy asbestos-exposed individuals (n = 89), and patients with benign asbestos-related disease (n = 123), benign respiratory disease (n = 46), lung cancer (n = 63), and MPM (n = 85). Sera were analyzed for SM and MPF levels using the Mesomark and Human MPF ELISA kit, respectively.SM and MPF levels differed significantly between patients with MPM and participants from each other cohort (P < 0.001). Receiver operating characteristics curve analysis did not reveal a significant difference between both markers in area under curve (AUC) for distinguishing MPM from all cohorts jointly (SM = 0.871, MPF = 0.849; P = 0.28). At 95% specificity, SM and MPF had a sensitivity of 64% (cutoff = 2.00 nmol/L) and 68% (cutoff = 12.38 ng/ml), respectively. Combining both markers did not improve the diagnostic performance.In this prospective multicenter study, MPF is validated as a highly performant MPM biomarker. The similar AUC values of SM and MPF, together with the limited difference in sensitivity, show that both serum biomarkers have an equivalent diagnostic performance.
Developmental Outcomes after Early or Delayed Insertion of Tympanostomy Tubes
Authors: Jack L. Paradise, Thomas F. Campbell, Christine A. Dollaghan, Heidi M. Feldman, Beverly S. Bernard, D. Kathleen Colborn, Howard E. Rockette, Janine E. Janosky, Dayna L. Pitcairn, Marcia Kurs-Lasky, Diane L. Sabo, Clyde G. Smith
Journal: New England Journal of Medicine (2005)

To prevent later developmental impairments, myringotomy with the insertion of tympanostomy tubes has often been undertaken in young children who have persistent otitis media with effusion. We previously reported that prompt as compared with delayed insertion of tympanostomy tubes in children with persistent effusion who were younger than three years of age did not result in improved developmental outcomes at three or four years of age. However, the effect on the outcomes of school-age children is unknown.
Diagnostic accuracy, safety and utilisation of respiratory physician-delivered thoracic ultrasound
Authors: N. M. Rahman, A. Singanayagam, H. E. Davies, J. M. Wrightson, E. K. Mishra, Y. C. G. Lee, R. Benamore, R. J. O. Davies, F. V. Gleeson
Journal: Thorax (2010)

<h3>Background</h3> Thoracic ultrasound-guided pleural procedures are associated with fewer adverse events than 'blind' procedures for patients with pleural effusion. Ultrasound is increasingly practised by respiratory physicians but there has been no prospective assessment of its safety and diagnostic accuracy when delivered by respiratory physicians. <h3>Methods</h3> The activity level, safety and diagnostic accuracy of thoracic ultrasound delivered by respiratory physicians were prospectively assessed. Diagnostic accuracy was assessed using a stepwise pragmatic approach (recording if pleural fluid was obtained or effusion was present on another radiological modality). In the absence of the above, ultrasound clips were reviewed by a blinded radiologist. The number of ultrasounds referred to radiologists and adverse events within 1 week were recorded. The complication rate was compared with the published literature. <h3>Results</h3> 960 ultrasound scans occurred over a 3 year period. The activity of the service increased over time, as a result of increased use of interventional ultrasound. The referral rate to radiology remained constant over the study period (mean proportion 4.0%). Physician-delivered ultrasound correctly identified the presence/absence of pleural fluid in 951 of 955 evaluable scans (99.6% CI 98.9% to 99.9%). The major complication rate was 3/558=0.5% (95% CI 0.1% to 1.6%), which compared favourably with the identified published literature. <h3>Conclusion</h3> Respiratory physician-delivered thoracic ultrasound appears to be safe and effective in the diagnosis/intervention of pleural effusion, and is associated with a major complication rate comparable with that of published studies. Continued liaison with the radiology service has here been demonstrated as a requirement for a physician-based service.
Genetic and Functional Analyses of Membrane Cofactor Protein (CD46) Mutations in Atypical Hemolytic Uremic Syndrome
Authors: Ve[Combining Acute Accent]ronique Fremeaux-Bacchi, Elizabeth A. Moulton, David Kavanagh, Marie-Agne[Combining Grave Accent]s Dragon-Durey, Jacques Blouin, Amy Caudy, Nadia Arzouk, Roxanna Cleper, Maud Francois, Genevieve Guest, Jacques Pourrat, Roland Seligman, Wolf Herman Fridman, Chantal Loirat, John P. Atkinson
Journal: Journal of the American Society of Nephrology (2006)

Hemolytic uremic syndrome (HUS) is characterized by the triad of thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure. The non–Shiga toxin–associated HUS (atypical HUS [aHUS]) has been shown to be a disease of complement dysregulation. Mutations in the plasma complement regulators factor H and factor I and the widely expressed membrane cofactor protein (MCP; CD46) have been described recently. This study looked for MCP mutations in a panel of 120 patients with aHUS. In this cohort, approximately 10% of patients with aHUS (11 patients; nine pedigrees) have mutations in MCP. The onset typically was in early childhood. Unlike patients with factor I or factor H mutations, most of the patients do not develop end-stage renal failure after aHUS. The majority of patients have a mutation that causes reduced MCP surface expression. A small proportion expressed normal levels of a dysfunctional protein. As in other studies, incomplete penetrance is shown, suggesting that MCP is a predisposing factor rather than a direct causal factor. The low level of recurrence of aHUS in transplantation in patients with MCP mutations is confirmed, and the first MCP null individuals are described. This study confirms the association between MCP deficiency and aHUS and further establishes that a deficiency in complement regulation, specifically cofactor activity, predisposes to severe thrombotic microangiopathy in the renal vasculature.
Bioresorbable Stents
Authors: John A. Bittl
Journal: Circulation (2010)

U sually elegant and sometimes ingenious, most innova- tions in interventional cardiology represent incremental advances.Quantum leaps are rare.A major transformation in practice occurred when bare metal stents (BMS) replaced balloon angioplasty, because stenting could scaffold intimal tears, reduce elastic recoil, and prevent negative remodeling. 1 Another breakthrough occurred when antiproliferative drugs eluted from stents nearly eliminated the neointimal growth response to stent implantation. 2A negative consequence of drug-eluting stents has been a low incidence of late stent thrombosis 3 caused by incomplete arterial healing and exposed metal struts left in contact with circulating blood. 4ecause the need for vessel-wall support after coronary intervention may be temporary, bioresorbable coronary stents might represent a solution to prevent late stent thrombosis.Bioresorbable drug-eluting stents could provide temporary scaffolding when it is needed after coronary intervention, reduce the risk of restenosis, and completely disappear without leaving thrombogenic residua.If the devices are user-friendly and regulatory requirements are satisfied, bioresorbable stents could revolutionize the practice of interventional cardiology.
Bone Morphogenetic Proteins, Their Antagonists, and the Skeleton
Authors: Ernesto Canalis, Aris N. Economides, Elisabetta Gazzerro
Journal: Endocrine Reviews (2003)

Skeletal homeostasis is determined by systemic hormones and local factors. Bone morphogenetic proteins (BMP) are unique because they induce the differentiation of mesenchymal cells toward cells of the osteoblastic lineage and also enhance the differentiated function of the osteoblast. However, the activity of BMPs needs to be tempered by intracellular and extracellular antagonists. BMPs bind to specific receptors and signal by phosphorylating the cytoplasmic proteins mothers against decapentaplegic (Smad) 1 and 5, which form heterodimers with Smad 4, and after nuclear translocation regulate transcription. BMP antagonists can be categorized as pseudoreceptors that compete with signaling receptors, inhibitory Smads that block signaling, intracellular binding proteins that bind Smad 1 and 5, and factors that induce ubiquitination and proteolysis of signaling Smads. In addition, a large number of extracellular proteins that bind BMPs and prevent their binding to signaling receptors have emerged. They are the components of the Spemann organizer, noggin, chordin, and follistatin, members of the Dan/Cerberus family, and twisted gastrulation. The antagonists tend to be specific for BMPs and are regulated by BMPs, indicating the existence and need of local feedback mechanisms to temper BMP cellular activities.
Deleterious influence of pyrazinamide on the outcome of patients with fulminant or subfulminant liver failure during antituberculous treatment including isoniazid
Authors: François Durand, Jacques Bernuau, Dominique Pessayre, Didier Samuel, Jacques Belaiche, Claude Degott, Henri Bismuth, Jacques Belghiti, Serge Erlinger, Bernard Rueff, Jean Pierre Benhamou
Journal: Hepatology (1995)

Isoniazid and pyrazinamide are well-known hepatotoxic drugs, often used in combination. The aim of this study was to assess the prognostic influence of pyrazinamide on the outcome of fulminant or subfulminant liver failure caused by antituberculous therapy. Eighteen patients with fulminant or subfulminant liver failure due to antituberculous therapy were studied. Nine patients received isoniazid and rifampicin without pyrazinamide (group 1), and nine patients received isoniazid and rifampicin together with pyrazinamide (group 2). The severity of fulminant and subfulminant liver failure, as judged by the prevalence of coma and the lowest level of factor V, was similar in the two groups. Spontaneous survival was greater in group 1 (eight of nine) than in group 2 (two of nine) (P < .02). The authors conclude that pyrazinamide co-administration was associated with an increased mortality in patients with fulminant or subfulminant hepatitis occurring during antituberculous therapy. In these patients, pyrazinamide administration and an interval of more than 15 days between the onset of antituberculous treatment and jaundice, combined with grade III encephalopathy and factor V below 20%, predicted death without liver transplantation.
The effect on mortality of antipyretics in the treatment of influenza infection: systematic review and meta-analyis
Authors: Sally Eyers, Mark Weatherall, Philippa Shirtcliffe, Kyle Perrin, Richard Beasley
Journal: Journal of the Royal Society of Medicine (2010)

Summary Objective To determine whether antipyretic treatment for influenza infection influences the risk of mortality in animal models and humans. Design A systematic search of Medline, Embase and the Cochrane Register of Controlled Trials was undertaken to identify randomized placebo-controlled trials of antipyretic use in influenza infection in animal models or humans that reported mortality. A quantitative meta-analysis of the risk of death using Peto's one step odds ratio with calculation of the pooled risk of death and standard evaluation of heterogeneity was undertaken. Setting Not applicable. Participants Not applicable. Main outcome measures Risk of mortality associated with antipyretic use in influenza infection. Results Eight studies from three publications met the inclusion criteria. No human studies were identified. The risk of mortality was increased by antipyretic use in influenza-infected animals with a fixed effects pooled odds ratio of 1.34 (95% CI 1.04–1.73). An increased risk was observed with aspirin, paracetamol and diclofenac. Conclusion In animal models, treatment with antipyretics for influenza infection increases the risk of mortality. There are no randomized placebo-controlled trials of antipyretic use in influenza infection in humans that reported data on mortality and a paucity of clinical data by which to assess their efficacy. We suggest that randomized placebo-controlled trials of antipyretic use in human influenza infection are urgently required, and that these are sufficiently powered to investigate a potential effect on mortality.
High prevalence of autoreactive, neuroantigen-specific CD8+ T cells in multiple sclerosis revealed by novel flow cytometric assay
Authors: Michael P. Crawford, Shirley X. Yan, Sterling B. Ortega, Riyaz S. Mehta, Rachel E. Hewitt, David A. Price, Peter Stastny, Daniel C. Douek, Richard A. Koup, Michael K. Racke, Nitin J. Karandikar
Journal: Blood (2004)