Search results for "sensitivity and specificity"
showing 10 items of 1080 documents
Direct evidence that FK506 inhibition of FcεRI-mediated exocytosis from RBL mast cells involves calcineurin
1998
eRI-mediated exocytosis of preformed mediators from mast cells and basophils (e.g. histamine, serotonin, beta-hexosaminidase) is sensitive to the immunosuppressants cyclosporin A and FK506 (IC 50 200 and 4 n M , respectively) but not rapamycin. The mechanism of inhibition does not appear to involve tyrosine phosphorylation, hydrolysis of inositol phosphates or calcium flux. Here we report experiments using a molecular approach to assess the role of calcineurin, a serine/threonine phosphatase thought to be the primary pharmacological target of these drugs. Calcineurin’s activity requires association of its catalytic (A) subunit with an intrinsic regulatory (B) subunit. We hypothesized that c…
Versatile, sensitive liquid chromatography mass spectrometry – Implementation of 10 μm OT columns suitable for small molecules, peptides and proteins
2016
AbstractWe have designed a versatile and sensitive liquid chromatographic (LC) system, featuring a monolithic trap column and a very narrow (10 μm ID) fused silica open tubular liquid chromatography (OTLC) separation column functionalized with C18-groups, for separating a wide range of molecules (from small metabolites to intact proteins). Compared to today’s capillary/nanoLC approaches, our system provides significantly enhanced sensitivity (up to several orders) with matching or improved separation efficiency, and highly repeatable chromatographic performance. The chemical properties of the trap column and the analytical column were fine-tuned to obtain practical sample loading capacities…
Proteomic Approaches in Colon Cancer: Promising Tools for New Cancer Markers and Drug Target Discovery
2005
Novel technologies are needed from which to identify new and more efficient biomarkers and improved molecular targets for the expedient and accurate diagnosis and treatment of colorectal cancer. Many advances have been made in direct and virtual imaging for detection of polyps and malignant-type lesions. These require tissue verification before definitive intervention. Inclusion of a simple serum test, more accurate than CEA, especially for early cancer detection, would make virtual imaging much more successful. Proteomics, the study of the proteins and protein pathways involved in disease, is a new dimension in preclinical and clinical development. Mass spectrometric analysis of serum prot…
Ultrahigh-Throughput Proteomics Using Fast RPLC Separations with ESI-MS/MS
2005
We describe approaches for proteomics analysis using electrospray ionization-tandem mass spectrometry coupled with fast reversed-phase liquid chromatography (RPLC) separations. The RPLC separations used 50-microm-i.d. fused-silica capillaries packed with submicrometer-sized C18-bonded porous silica particles and achieved peak capacities of 130-420 for analytes from proteome tryptic digests. When these separations were combined with linear ion trap tandem mass spectrometry measurements, approximately 1000 proteins could be identified in 50 min from approximately 4000 identified tryptic peptides; approximately 550 proteins in 20 min from approximately 1800 peptides; and approximately 250 prot…
Establishing PNB-qPCR for quantifying minimal ctDNA concentrations during tumour resection.
2017
The analysis of blood plasma or serum as a non-invasive alternative to tissue biopsies is a much-pursued goal in cancer research. Various methods and approaches have been presented to determine a patient’s tumour status, chances of survival, and response to therapy from serum or plasma samples. We established PNB-qPCR (Pooled, Nested, WT-Blocking qPCR), a highly specific nested qPCR with various modifications to detect and quantify minute amounts of circulating tumour DNA (ctDNA) from very limited blood plasma samples. PNB-qPCR is a nested qPCR technique combining ARMS primers, blocking primers, LNA probes, and pooling of multiple first round products for sensitive quantification of the sev…
Bidirectional Glenn and antegrade pulmonary blood flow: temporary or definitive palliation?
2008
Background We sought to investigate the role of the bidirectional Glenn with antegrade pulmonary blood flow in the surgical history of children with univentricular hearts. Methods A series of 246 patients, from three joint institutions, having univentricular heart with restricted but not critical pulmonary blood flow received a bidirectional cavopulmonary shunt with additional forward pulmonary blood flow. All patients have been studied according to their progression, or not, to Fontan operation. Two hundred and eight (84.5%) patients underwent bidirectional cavopulmonary anastomosis as primary palliation. Twenty patients (8.1%) with previous pulmonary artery banding were also enrolled in t…
Blood pressure responsiveness to obstructive events during sleep after chronic CPAP
2003
The aim of this study was to investigate whether chronic continuous positive airway pressure (CPAP) affects blood pressure (BP) responsiveness to obstructive events occurring on the first night of CPAP withdrawal in obstructive sleep apnoea (OSA) after chronic treatment. Thirteen male subjects with severe OSA underwent nocturnal polysomnography with beatbybeat BP monitoring before treatment and after 4.9±3.4 months of home CPAP (mean daily use 5.1±1.7 h). Variations in oxyhaemoglobin saturation (Δ S a,O2), systolic (Δ P s), and diastolic (Δ P d) BP within nonrapid eye movement apnoeas and hypopnoeas were measured on a sample of pre and posttreatment events. In addition, a pretreatment s…
Soot-exposed mononuclear cells increase inflammatory cytokine mRNA expression and protein secretion in cocultured bronchial epithelial cells.
2000
<i>Background:</i> Soot particles are air pollutants capable of inducing airway and lung parenchymal injury. Mononuclear and bronchial epithelial cells are central to the maintenance of homeostasis and inflammation in the airways. <i>Objectives:</i> The aim of this study was to evaluate the contribution of mononuclear cells to the release of inflammatory mediators by bronchial epithelial cells. <i>Methods:</i> To model the in vivo situation, an in vitro system of cocultured blood monocytes and BEAS-2B cells was established in a transwell system. Blood monocytes were exposed to soot particles (FR 101) at concentrations of up to 100 μg/10<sup>6</su…
Prediction of bleeding events in patients with venous thromboembolism on stable anticoagulation treatment.
2016
Attempts at identifying patients with an elevated risk of bleeding while on anticoagulation following acute venous thromboembolism (VTE) have largely been unsuccessful thus far. We sought to develop a clinical prediction score for bleeding during stable anticoagulation treatment after acute VTE.We performed a post hoc analysis of the pooled RE-COVER studies, two double-blind randomised “sister” trials evaluating dabigatran versus standard treatment in 5107 VTE patients.A score was derived from patients randomised to dabigatran using logistic regression analysis covering the complete follow-up period. The final model, named VTE-BLEED, included six variables and yielded a c-statistic of 0.72 …
Mediastinal lymph node staging with transesophageal echography in cancer of the lung.
1990
Transesophageal echography (TEE) was used prospectively to study mediastinal lymph node enlargement in 23 patients with cancer of the lung. The findings were validated blindly by comparison with computed tomography (CT, n = 23) and pathological N classification after curative surgery (n = 9). Lymph nodes larger than 1 cm were defined as pathologically enlarged. In the upper mediastinum, 22% (8 vs 36), in the lower mediastinum including the subaortic region 112% (37 vs 33) and in the hilar region 67% (6 vs 9) of enlarged lymph nodes diagnosed by CT were detected by TEE. A pathological study in 9 patients demonstrated true positive findings in 2 vs 1, true negatives in 4 vs 5, false positives…