tbuckley/cabot-search huggingface dataset:
Efficacy and Safety of Edifoligide, an E2F Transcription Factor Decoy, for Prevention of Vein Graft Failure Following Coronary Artery Bypass Graft Surgery
Authors: John H Alexander, Gail Hafley, Robert A Harrington, Eric D Peterson, T Bruce Ferguson, Todd J Lorenz, Abhinav Goyal, Michael Gibson, Michael J Mack, Daniel Gennevois, Robert M Califf, Nicholas T Kouchoukos
Journal: JAMA (2005)

Coronary artery bypass graft (CABG) surgery with autologous vein grafting is commonly performed. Progressive neointimal hyperplasia, however, contributes to considerable vein graft failure. Edifoligide is an oligonucleotide decoy that binds to and inhibits E2F transcription factors and thus may prevent neointimal hyperplasia and vein graft failure.To assess the efficacy and safety of pretreating vein grafts with edifoligide for patients undergoing CABG surgery.A phase 3 randomized, double-blind, placebo-controlled trial of 3014 patients undergoing primary CABG surgery with at least 2 planned saphenous vein grafts and without concomitant valve surgery, who were enrolled between August 2002 and October 2003 at 107 US sites.Vein grafts were treated ex vivo with either edifoligide or placebo in a pressure-mediated delivery system. The first 2400 patients enrolled were scheduled for 12- to 18-month follow-up angiography.The primary efficacy end point was angiographic vein graft failure (> or =75% vein graft stenosis) occurring 12 to 18 months after CABG surgery. Other end points included other angiographic variables, adverse events through 30 days, and major adverse cardiac events.A total of 1920 patients (80%) either died (n = 91) or underwent follow-up angiography (n = 1829). Edifoligide had no effect on the primary end point of per patient vein graft failure (436 [45.2%] of 965 patients in the edifoligide group vs 442 [46.3%] of 955 patients in the placebo group; odds ratio, 0.96 [95% confidence interval {CI}, 0.80-1.14]; P = .66), on any secondary angiographic end point, or on the incidence of major adverse cardiac events at 1 year (101 [6.7%] of 1508 patients in the edifoligide group vs 121 [8.1%] of 1506 patients in the placebo group; hazard ratio, 0.83 [95% CI, 0.64-1.08]; P = .16).Failure of at least 1 vein graft is quite common within 12 to 18 months after CABG surgery. Edifoligide is no more effective than placebo in preventing these events. Longer-term follow-up and additional research are needed to determine whether edifoligide has delayed beneficial effects, to understand the mechanisms and clinical consequences of vein graft failure, and to improve the durability of CABG surgery. Clinical Trial Registration ClinicalTrials.gov Identifier: NCT00042081.
Apolipoprotein B Attenuates Albuminuria-Associated Cardiovascular Disease in Prevention of Renal and Vascular Endstage Disease (PREVEND) Participants
Authors: James P. Corsetti, Ron T. Gansevoort, Stephan J.L. Bakker, Charles E. Sparks, Priya Vart, Robin P.F. Dullaart
Journal: Journal of the American Society of Nephrology (2014)

Whether urinary albumin excretion relates to higher levels of atherogenic apolipoprotein B fractions in the nondiabetic population is uncertain. Such a relationship could explain, in part, the association of elevated urinary albumin excretion with cardiovascular disease risk. We assessed the relationship of urinary albumin excretion with apolipoprotein B fractions and determined whether the association of elevated urinary albumin excretion with incident cardiovascular events is modified by high apolipoprotein B fraction levels. We performed a prospective study on 8286 nondiabetic participants (580 participants with cardiovascular disease; 4.9 years median follow-up time) with fasting lipids, apolipoprotein B, and urinary albumin excretion determined at baseline. With adjustment for sex and age, micro- and macroalbuminuria were associated with increased apolipoprotein B fractions (non-HDL cholesterol, LDL cholesterol, triglycerides, and apolipoprotein B). All four apolipoprotein B fractions modified associations of urinary albumin excretion with incident cardiovascular disease (hazard ratios for interaction terms ranged from 0.89 to 0.94 with 95% confidence intervals ranging from 0.84 to 0.99 and P values ranging from 0.001 to 0.02 by Cox proportional hazards modeling). These interactions remained present after additional adjustment for conventional risk factors, eGFR, cardiovascular history, and lipid-lowering and antihypertensive drug treatments. Such modification was also observed when urinary albumin excretion was stratified into normo-, micro-, and macroalbuminuria. We conclude that there is an association between elevated urinary albumin excretion and apolipoprotein B fraction levels and a negative interaction between these variables in their associations with incident cardiovascular events. Elevated urinary albumin excretion may share common causal pathways with high apolipoprotein B fractions in the pathogenesis of cardiovascular disease.
Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study
Authors: Karthikeyan K Kumarasamy, Mark A Toleman, Timothy R Walsh, Jay Bagaria, Fafhana Butt, Ravikumar Balakrishnan, Uma Chaudhary, Michel Doumith, Christian G Giske, Seema Irfan, Padma Krishnan, Anil V Kumar, Sunil Maharjan, Shazad Mushtaq, Tabassum Noorie, David L Paterson, Andrew Pearson, Claire Perry, Rachel Pike, Bhargavi Rao, Ujjwayini Ray, Jayanta B Sarma, Madhu Sharma, Elizabeth Sheridan, Mandayam A Thirunarayan, Jane Turton, Supriya Upadhyay, Marina Warner, William Welfare, David M Livermore, Neil Woodford
Journal: The Lancet Infectious Diseases (2010)

BackgroundGram-negative Enterobacteriaceae with resistance to carbapenem conferred by New Delhi metallo-β-lactamase 1 (NDM-1) are potentially a major global health problem. We investigated the prevalence of NDM-1, in multidrug-resistant Enterobacteriaceae in India, Pakistan, and the UK.MethodsEnterobacteriaceae isolates were studied from two major centres in India—Chennai (south India), Haryana (north India)—and those referred to the UK's national reference laboratory. Antibiotic susceptibilities were assessed, and the presence of the carbapenem resistance gene blaNDM-1 was established by PCR. Isolates were typed by pulsed-field gel electrophoresis of XbaI-restricted genomic DNA. Plasmids were analysed by S1 nuclease digestion and PCR typing. Case data for UK patients were reviewed for evidence of travel and recent admission to hospitals in India or Pakistan.FindingsWe identified 44 isolates with NDM-1 in Chennai, 26 in Haryana, 37 in the UK, and 73 in other sites in India and Pakistan. NDM-1 was mostly found among Escherichia coli (36) and Klebsiella pneumoniae (111), which were highly resistant to all antibiotics except to tigecycline and colistin. K pneumoniae isolates from Haryana were clonal but NDM-1 producers from the UK and Chennai were clonally diverse. Most isolates carried the NDM-1 gene on plasmids: those from UK and Chennai were readily transferable whereas those from Haryana were not conjugative. Many of the UK NDM-1 positive patients had travelled to India or Pakistan within the past year, or had links with these countries.InterpretationThe potential of NDM-1 to be a worldwide public health problem is great, and co-ordinated international surveillance is needed.FundingEuropean Union, Wellcome Trust, and Wyeth.
iTRAQ-based proteomic identification of leucine-rich -2 glycoprotein as a novel inflammatory biomarker in autoimmune diseases
Authors: S. Serada, M. Fujimoto, A. Ogata, F. Terabe, T. Hirano, H. Iijima, S. Shinzaki, T. Nishikawa, T. Ohkawara, K. Iwahori, N. Ohguro, T. Kishimoto, T. Naka
Journal: Annals of the Rheumatic Diseases (2009)

<h3>Objective</h3> To identify a novel serum biomarker of disease activity in inflammatory autoimmune disorders. <h3>Methods</h3> Sera obtained from rheumatoid arthritis (RA) patients before and after anti-TNF therapy were analysed by iTRAQ (isobaric tags for relative and absolute quantitation) quantitative proteomic analysis and further validated by ELISA. <h3>Results</h3> Of 326 proteins identified by proteomic analysis, increased serum levels of leucine-rich α-2 glycoprotein (LRG) was identified in RA patients before therapy. Serum LRG concentrations were significantly elevated in RA patients compared with healthy controls and decreased after anti-TNF therapy. Furthermore, serum LRG concentrations correlated with disease activity in RA and Crohn9s disease (CD). Interestingly, in a subpopulation of patients with active CD and normal C-reactive protein levels, serum LRG concentrations were elevated. <h3>Conclusions</h3> LRG represents a novel serum biomarker for monitoring disease activity during therapy in autoimmune patients, particularly useful in patients with active disease but normal CRP levels.
Sleep-Disordered Breathing, Control of Breathing, Respiratory Muscles, Pulmonary Function Testing in <i>AJRCCM</i> 2003
Authors: Martin J. Tobin
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Sleep-disordered Breathing (41) Epidemiology (5) Risk Factors (1) Pathophysiology (17) Cardiovascular Mechanisms (4) Upper Airway Mechanisms (7) Control of Breathing (6) Clinical Aspects (5) In Critically Ill Patients (1) In Children (4) Diagnostic Techniques (1) Treatment (12) Airway Pressure and Flow (5) Pharmacotherapy (4) Mandibular Devices (1) Surgery (1) Obesity Management (1) Control of Breathing (8) Studies in Animals (3) Pathophysiological Studies in Volunteers (3) Control of Breathing in Clinical Disorders (2) Respiratory Muscles (18) Studies in Animals (1) Mechanical Ventilation (1) Pathophysiological Studies in Patients and Volunteers (17) Exercise and Peripheral Muscles (8) Chest Wall Motion (2) Diagnostic Studies (1) Respiratory Muscle Involvement in Clinical Disorders (6) Pulmonary Function Testing and Bronchoscopy (14) Equipment and Techniques (1) Epidemiologic and Genetic Studies (2) Preoperative (1) In Diabetes Mellitus (1) In Thalassemia (1) Physical Fitness (1) Bronchoscopy (7)
Genomic Correlates to the Newly Proposed Grading Prognostic Groups for Prostate Cancer
Authors: Mark A. Rubin, Gabriele Girelli, Francesca Demichelis
Journal: European Urology (2015)

Recommendations by the International Society of Urologic Pathology and 2016 World Health Organization blue book propose the use of a five-tiered prostate cancer (PCa) grading system. The five prognostic grade groupings (PGGs) ranging from 1 to 5 are defined as Gleason grades ≤6, 3 + 4, 4 + 3, 8, and >8, respectively. Recent work suggests that each group is associated with a distinct risk of biochemical PCa recurrence. In this study, we sought genomic support for PGGs using whole-exome and whole-genome sequencing data for 426 clinically localized PCas treated by radical prostatectomy. After adjustment for tumor purity for the sequencing data, we observed a significant frequency increase in genomic amplifications and deletions (p = 0.013) and in nonsynonymous point mutations (p = 0.008) with increasing risk group. Interestingly, PGG1 (low risk) was entirely haploid, whereas PGG2–5 exhibited increasing polyploidy frequency. Principal component analysis of genomic profiles revealed that PGG1, PGG2, and PGG3 represent distinct classes, but PGG4 and PGG5 exhibit genomic similarity. Together, these observations for the largest PCa genomic data set to date provide support for increasing genomic alterations with increasing PGG. This is the first genomic correlation of the PGG system. Future work will need to explore the clinical utility of PGGs in prospective studies with long-term follow-up. Gleason grading for prostate cancer provides important information for guiding clinical care. A new proposal by leading pathologists favors translating Gleason grades into five risk categories. In this study, a comprehensive analysis of the largest genomic data set on prostate cancer to date, we demonstrate molecular support for this new five-tiered system.
Transcriptional Regulation of Cyclin A2 by RASSF1A through the Enhanced Binding of p120E4F to the Cyclin A2 Promoter
Authors: Jalal Ahmed-Choudhury, Angelo Agathanggelou, Sarah L. Fenton, Christopher Ricketts, Geoffrey J. Clark, Eamonn R. Maher, Farida Latif
Journal: Cancer Research (2005)

Abstract Recent advances in the study of RASSF1A, the candidate tumor suppressor gene, indicate a possible role of RASSF1A in cell cycle regulation; however, very little is known regarding molecular mechanisms underlying this control. Using small interfering RNA to knockdown endogenous RASSF1A in the breast tumor cell line HB2 and in the cervical cancer cell line HeLa, we identify that a key player in cell cycle progression, cyclin A2, is concomitantly increased at both protein and mRNA levels. In A549 clones stably expressing RASSF1A, cyclin A2 levels were diminished compared with vector control. A known transcriptional regulator of cyclin A2, p120E4F (a repressor of cyclin A2), has been shown previously by our group to interact with RASSF1A. We show that levels of p120E4F are not affected by RASSF1A small interfering RNA in HB2 and HeLa cells. However, electrophoretic mobility shift assays indicate that knockdown of endogenous RASSF1A in HB2 and HeLa cells leads to a reduction in the binding capacity of p120E4F to the cyclin A2 promoter, whereas in the A549 clone stably expressing RASSF1A the binding capacity is increased. These data are further corroborated in vitro by the luciferase assay and in vivo by chromatin immunoprecipitation experiments. Together, these data identify the cyclin A2 gene as a cellular target for RASSF1A through p120E4F and for the first time suggest a transcriptional mechanism for RASSF1A-dependent cell cycle regulation.
Antipsychotic Treatment in Breast Cancer Patients
Authors: Tahir Rahman, Charles V. Clevenger, Virginia Kaklamani, John Lauriello, Austin Campbell, Kari Malwitz, Robert S. Kirkland
Journal: American Journal of Psychiatry (2014)

Special consideration is required when prescribing antipsychotic drugs for patients with an existing diagnosis of breast cancer. The package inserts of all approved antipsychotics contain precautions regarding their administration in this patient group. These drugs are well known to elevate serum prolactin levels to varying degrees. Overexpression of the prolactin receptor is seen in more than 95% of human breast cancers. Many genes that are activated by the prolactin receptor are associated with tumorigenesis and cancer cell proliferation. The authors discuss the pathophysiology, clinical implications, and pertinent preclinical data and make specific recommendations regarding the use of antipsychotics in patients with breast cancer.
802-5 Long-term prognostic value of pacing stress echocardiography compared with dipyridamole Tl 201 tomography in patients with permanent pacemaker and known or suspected coronary artery disease
Authors: Sarah Shimoni, Sorel Goland, Shay Livshitz, Gera Gendelman, Avraham Caspi, Menashe Epstein
Journal: Journal of the American College of Cardiology (2004)
Optimizing management of ruxolitinib in patients with myelofibrosis: the need for individualized dosing
Authors: Ruben A Mesa, Jorge Cortes
Journal: Journal of Hematology & Oncology (2013)

Ruxolitinib, an oral JAK1 and JAK2 inhibitor, is approved in the US for patients with intermediate or high-risk myelofibrosis (MF), a chronic neoplasm associated with aberrant myeloproliferation, progressive bone marrow fibrosis, splenomegaly, and burdensome symptoms. Phase III clinical studies have shown that ruxolitinib reduces splenomegaly and alleviates MF-related symptoms, with concomitant improvements in quality of life measures, for the overwhelming majority of treated patients. In addition, ruxolitinib provided an overall survival advantage as compared with either placebo or what was previously considered best available therapy in the two phase III studies. The most common adverse events with ruxolitinib treatment include dose-dependent anemia and thrombocytopenia, which are expected based on its mechanism of action. Experience from the phase III studies shows that these hematologic events can be managed effectively with dose modifications, temporary treatment interruptions, as well as red blood cell transfusions in the case of anemia and, importantly, are rarely cause for permanent treatment discontinuation. This review summarizes data supporting appropriate individualized patient management through careful monitoring of blood counts and dose titration as needed in order to maximize treatment benefit.
Relationship between plasma cell levels and profile of bronchoalveolar lavage fluid in patients with subacute extrinsic allergic alveolitis.
Authors: M Drent, S Wagenaar, H van Velzen-Blad, P G Mulder, H C Hoogsteden, J M van den Bosch
Journal: Thorax (1993)

BACKGROUND--Plasma cells are usually absent in bronchoalveolar lavage (BAL) fluid. Extrinsic allergic alveolitis is associated with increased numbers of T and B lymphocytes in BAL fluid, as well as the presence of a few plasma cells. The aim of this study was to investigate whether there is a relationship between the presence of plasma cells and other cells, and immunoglobulin levels in BAL fluid of patients with extrinsic allergic alveolitis. METHODS--Thirty non-smoking patients with extrinsic allergic alveolitis who had a bronchoalveolar lavage 2-7 days after their last exposure to the causative antigen were selected, retrospectively. RESULTS--Patients suffering from extrinsic allergic alveolitis with plasma cells in the BAL fluid (n = 18) had increased absolute numbers of lymphocytes, eosinophils and mast cells, a decreased percentage of alveolar macrophages and lower CD4/CD8 ratio, as well as higher immunoglobulin levels, when compared with patients with extrinsic allergic alveolitis having no plasma cells in the BAL fluid (n = 12). CONCLUSIONS--The results suggest a relationship between the presence of plasma cells and the other constituents in BAL fluid and a more intense alveolitis. In addition there was a positive relationship between the number of plasma cells in BAL fluid and immunoglobulin levels. These data support the concept of local production of immunoglobulins by plasma cells in the lung following antigen exposure in susceptible individuals.
FRI0189 A preliminary algorithm introducing immunogenicity assessment in the management of ra patients receiving biotechnological therapies
Authors: S. Garcês, M. Antunes, E. Benito-Garcia, J. Canas-Silva, L. Aarden, J. Demengeot
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Clinical remission is today the treatment goal for Rheumatoid Arthritis (RA), which requires fast and assertive therapeutic decisions for a tight control of disease activity. Few objective parameters are available to guide clinical decisions, namely in switcher patients. We designed a preliminary algorithm introducing immunogenicity assessment in the current approach to RA patients receiving biotechnologic therapies. <h3>Objectives</h3> To evaluate the concordance between the new algorithm and current clinical practice, comparing the effectiveness of "immunogenicity-based" versus "empirical-based" switches in a cohort of patients with established RA receiving biologics. <h3>Methods</h3> EULAR therapeutic response was evaluated in 105 RA patients (naive or switchers) over one year, through GEE analysis. Serum drug trough levels were assessed by ELISA and anti-drug antibodies (ADA) by Bridging ELISA. <h3>Results</h3> During follow-up, 48.6% of patients (Group A) had concordant therapeutic decisions. One year after the therapeutic decision, patients from Group A had a higher probability of achieving response (OR=7.91, <i>p</i>&lt;0.001, 95%CI=3.27-19.13) and low disease activity (OR=9.77, <i>p</i>&lt;0.001, 95%CI=4.69-20.37). <h3>Image/graph</h3> <h3>Conclusions</h3> Immunogenicity assessment might help to optimize therapeutic decisions, leading to a better control of disease activity with significant better clinical outcomes in RA patients receiving biotechnologic therapies. <h3>Disclosure of Interest</h3> None Declared
THE NAILS IN PSORIATIC ARTHRITIS.
Authors: H. BAKER, D.N. GOLDING, M. THOMPSON
Journal: British Journal of Dermatology (1964)

Journal Article THE NAILS IN PSORIATIC ARTHRITIS. Get access H. BAKER, H. BAKER Senior Registrar, Department of Dermatology, The London Hospital Search for other works by this author on: Oxford Academic Google Scholar D.N. GOLDING, D.N. GOLDING Formerly Senior Registrar, Department of Physical Medicine, Royal Free Hospital. London Search for other works by this author on: Oxford Academic Google Scholar M. THOMPSON M. THOMPSON Physician‐in‐Charge, Department of Physical Medicine, Royal Victoria Infirmary, Newcastle‐Upon‐Tyne,1 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 76, Issue 12, 1 December 1964, Pages 549–554, https://doi.org/10.1111/j.1365-2133.1964.tb15505.x Published: 01 December 1964
Effect of cetirizine on exercise induced asthma.
Authors: S K Ghosh, C De Vos, I McIlroy, K R Patel
Journal: Thorax (1991)

The effect of oral and inhaled cetirizine, a potent and specific H1 receptor antagonist, was studied in patients with exercise induced asthma. Twelve patients (five male; mean age 35.2 years) were given oral placebo or cetirizine 10 mg twice daily for one week, double blind and in randomised order, and exercised on a treadmill for six to eight minutes at a submaximal work load two hours after the final dose. There was no significant change in baseline FEV1 after treatment and cetirizine failed to inhibit exercise induced bronchoconstriction (maximum falls in FEV1 28% and 27% of baseline). In a further eight patients (four male; mean age 40.8 years) the effect of 1 ml cetirizine (5 and 10 mg/ml) given through a Wright nebuliser was compared with that of placebo in a double blind trial. The fall in FEV1 after exercise was reduced after both concentrations of cetirizine by 15.2% of baseline after 5 mg/ml and by 10.2% after 10 mg/ml, compared with 23.7% after placebo. In two patients cetirizine had no effect. In a further study cetirizine (10 mg/ml) given by inhalation displaced the geometric mean PC20 histamine 13.1 fold to the right by comparison with placebo. The reason for the difference between the effects of oral and of inhaled cetirizine on exercise asthma is not clear but may be related to differences in local concentration in the airway.
Identification of Human Regulatory T Cells in the Setting of T-Cell Activation and Anti–CTLA-4 Immunotherapy on the Basis of Expression of Latency-Associated Peptide
Authors: Jingjing Sun, Derek Ng Tang, Tihui Fu, Padmanee Sharma
Journal: Cancer Discovery (2011)

Effector and regulatory T cells (Treg) share multiple markers that make it difficult to discern differences in these populations in humans. The transcription factor FoxP3 has been shown to identify Tregs. However, the detection of FoxP3 requires cell permeabilization, thereby preventing isolation of viable Tregs. Subsequently, the extracellular marker CD127 was established for the identification of Tregs. However, these studies were not conducted in the setting of immunotherapy. Here, we conducted studies to analyze CD127 and FoxP3 expression on T cells before and after in vitro activation as well as in the setting of patients treated with antibodies directed against cytotoxic T-lymphocyte antigen-4 (CTLA-4). We show that latency-associated peptide (LAP), as opposed to CD127, was capable of identifying Tregs after in vitro activation as well as after treatment with anti-CTLA-4. Therefore, we propose that LAP should be used as a marker of Tregs for immune monitoring studies in patients treated with active immunotherapy such as anti-CTLA-4.Tregs play an important role in human diseases, including cancer and autoimmunity; however, it has been difficult to study these cells because of a lack of an appropriate marker. Here, we propose LAP as a marker that can be used to identify Tregs in patients treated with immunotherapy, thereby permitting isolation of these cells for functional studies and for ex vivo expansion.