69 resultados para FLUORESCENT-PROBE
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INTRODUCTION Vasospastic brain infarction is a devastating complication of aneurysmal subarachnoid hemorrhage (SAH). Using a probe for invasive monitoring of brain tissue oxygenation or blood flow is highly focal and may miss the site of cerebral vasospasm (CVS). Probe placement is based on the assumption that the spasm will occur either at the dependent vessel territory of the parent artery of the ruptured aneurysm or at the artery exposed to the focal thick blood clot. We investigated the likelihood of a focal monitoring sensor being placed in vasospasm or infarction territory on a hypothetical basis. METHODS From our database we retrospectively selected consecutive SAH patients with angiographically proven (day 7-14) severe CVS (narrowing of vessel lumen >50%). Depending on the aneurysm location we applied a standard protocol of probe placement to detect the most probable site of severe CVS or infarction. We analyzed whether the placement was congruent with existing CVS/infarction. RESULTS We analyzed 100 patients after SAH caused by aneurysms located in the following locations: MCA (n = 14), ICA (n = 30), A1CA (n = 4), AcoA or A2CA (n = 33), and VBA (n = 19). Sensor location corresponded with CVS territory in 93% of MCA, 87% of ICA, 76% of AcoA or A2CA, but only 50% of A1CA and 42% of VBA aneurysms. The focal probe was located inside the infarction territory in 95% of ICA, 89% of MCA, 78% of ACoA or A2CA, 50% of A1CA and 23% of VBA aneurysms. CONCLUSION The probability that a single focal probe will be situated in the territory of severe CVS and infarction varies. It seems to be reasonably accurate for MCA and ICA aneurysms, but not for ACA or VBA aneurysms.
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Long-term surface ECG is routinely used to diagnose paroxysmal arrhythmias. However, this method only provides information about the heart's electrical activity. To this end, we investigated a novel esophageal catheter that features synchronous esophageal ECG and acceleration measurements, the latter being a record of the heart's mechanical activity. The acceleration data were quantified in a small study and successfully linked to the activity sequences of the heart in all subjects. The acceleration signals were additionally transformed into motion. The extracted cardiac motion was proved to be a valid reference input for an adaptive filter capable of removing relevant baseline wandering in the recorded esophageal ECGs. Taking both capabilities into account, the proposed recorder might be a promising tool for future long-term heart monitoring.
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Background:Recently, fibroblast growth factor receptor 1 (FGFR1) was discovered in squamous cell carcinomas (SCC) of the lung with FGFR1 amplification described as a promising predictive marker for anti-FGFR inhibitor treatment. Only few data are available regarding prevalence, prognostic significance and clinico-pathological characteristics of FGFR1-amplified and early-stage non-small cell lung carcinomas (NSCLC). We therefore investigated the FGFR1 gene status in a large number of well-characterised early-stage NSCLC.Methods:FGFR1 gene status was evaluated using a commercially available fluorescent in situ hybridisation (FISH) probe on a tissue microarray (TMA). This TMA harbours 329 resected, formalin-fixed and paraffin-embedded, nodal-negative NSCLC with a UICC stage I-II. The FISH results were correlated with clinico-pathological features and overall survival (OS).Results:The prevalence of an FGFR1 amplification was 12.5% (41/329) and was significantly (P<0.0001) higher in squamous cell carcinoma (SCC) (20.7%) than in adenocarcinoma (2.2%) and large cell carcinoma (13%). Multivariate analysis revealed significantly (P=0.0367) worse 5-year OS in patients with an FGFR1-amplified NSCLC.Conclusions:FGFR1 amplification is common in early-stage SCC of the lung and is an independent and adverse prognostic marker. Its potential role as a predictive marker for targeted therapies or adjuvant treatment needs further investigation.
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INTRODUCTION Hemodynamic management in intensive care patients guided by blood pressure and flow measurements often do not sufficiently reveal common hemodynamic problems. Trans-esophageal echocardiography (TEE) allows for direct measurement of cardiac volumes and function. A new miniaturized probe for TEE (mTEE) potentially provides a rapid and simplified approach to monitor cardiac function. The aim of the study was to assess the feasibility of hemodynamic monitoring using mTEE in critically ill patients after a brief operator training period. METHODS In the context of the introduction of mTEE in a large ICU, 14 ICU staff specialists with no previous TEE experience received six hours of training as mTEE operators. The feasibility of mTEE and the quality of the obtained hemodynamic information were assessed. Three standard views were acquired in hemodynamically unstable patients: 1) for assessment of left ventricular function (LV) fractional area change (FAC) was obtained from a trans-gastric mid-esophageal short axis view, 2) right ventricular (RV) size was obtained from mid-esophageal four chamber view, and 3) superior vena cava collapsibility for detection of hypovolemia was assessed from mid-esophageal ascending aortic short axis view. Off-line blinded assessment by an expert cardiologist was considered as a reference. Inter-rater agreement was assessed using Chi-square tests or correlation analysis as appropriate. RESULTS In 55 patients, 148 mTEE examinations were performed. Acquisition of loops in sufficient quality was possible in 110 examinations for trans-gastric mid-esophageal short axis, 118 examinations for mid-esophageal four chamber and 125 examinations for mid-esophageal ascending aortic short axis view. Inter-rater agreement (Kappa) between ICU mTEE operators and the reference was 0.62 for estimates of LV function, 0.65 for RV dilatation, 0.76 for hypovolemia and 0.77 for occurrence of pericardial effusion (all P < 0.0001). There was a significant correlation between the FAC measured by ICU operators and the reference (r = 0.794, P (one-tailed) < 0.0001). CONCLUSIONS Echocardiographic examinations using mTEE after brief bed-side training were feasible and of sufficient quality in a majority of examined ICU patients with good inter-rater reliability between mTEE operators and an expert cardiologist. Further studies are required to assess the impact of hemodynamic monitoring by mTEE on relevant patient outcomes.
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A measurement of angular correlations in Drell-Yan lepton pairs via the phi(eta)* observable is presented. This variable probes the same physics as the Z/gamma* boson transverse momentum with a better experimental resolution. The Z/gamma* -> e(+)e(-) and Z/gamma* -> mu(+)mu(-) decays produced in proton-proton collisions at a centre-of-mass energy of root s = 7 TeV are used. The data were collected with the ATLAS detector at the LHC and correspond to an integrated luminosity of 4.6 fb(-1). Normalised differential cross sections as a function of phi(eta)* are measured separately for electron and muon decay channels. These channels are then combined for improved accuracy. The cross section is also measured double differentially as a function of phi(eta)* for three independent bins of the Z boson rapidity. The results are compared to QCD calculations and to predictions from different Monte Carlo event generators. The data are reasonably well described, in all measured Z boson rapidity regions, by resummed QCD predictions combined with fixed-order perturbative QCD calculations or by some Monte Carlo event generators. The measurement precision is typically better by one order of magnitude than present theoretical uncertainties.
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STUDY OBJECTIVE To determine the effectiveness of an esophageal doppler device to non-invasively detect experimental pseudo-electromechanical dissociation (pseudo-EMD). DESIGN Prospective, controlled, laboratory investigation using an asphyxial canine cardiac arrest model and a newly-developed esophageal flat-flow probe doppler unit. INTERVENTIONS Mongrel dogs (20) were instrumented for hemodynamic monitoring. The esophageal doppler probe was placed in the distal esophagus of each animal. Electromechanical dissociation (EMD) was induced by clamping the endotracheal tube. MEASUREMENTS AND MAIN RESULTS A period of pseudo-EMD was defined as the time where cardiac contractility was present, measured by a micromanometer tipped thoracic aortic catheter, without concurrent femoral pulses by palpation. The pseudo-EMD period could be produced consistently in all 20 animals. The characteristic doppler flow sounds were easily heard using the esophageal device in all animals. The time from endotracheal tube clamping until loss of femoral pulses was 622 +/- 96 s; until loss of radial artery doppler signals was 616 +/- 92 s; until loss of esophageal doppler signals was 728 +/- 88 s; and until loss of aortic fluctuations by thoracic aortic catheter was 728 +/- 82 s. The times to loss of esophageal doppler sounds and loss of aortic fluctuations were not significantly different. However, they were significantly longer than the time to loss of femoral pulses (P < 0.02). CONCLUSIONS The canine asphyxial EMD model can be used for short experimental studies of pseudo-EMD. Pseudo-EMD can be consistently and non-invasively detected with this esophageal doppler device. The device is as reliable as a micromanometer tipped aortic arch catheter in detecting pseudo-EMD. The doppler device could potentially be useful in improving recognition of near cardiac arrest in pre-hospital and emergency department settings. Further research on the utility of this device in other models of low-flow states should be performed.
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The pharmacological characterization of ligands depends upon the ability to accurately measure their binding properties. Fluorescence provides an alternative to more traditional approaches such as radioligand binding. Here we describe the binding and spectroscopic properties of eight fluorescent 5-HT3 receptor ligands. These were tested on purified receptors, expressed receptors on live cells, or in vivo. All compounds had nanomolar affinities with fluorescent properties extending from blue to near infra-red emission. A fluorescein-derivative had the highest affinity as measured by fluorescence polarization (FP; 1.14 nM), flow cytometry (FC; 3.23 nM) and radioligand binding (RB; 1.90 nM). Competition binding with unlabeled 5-HT3 receptor agonists (5-HT, mCPBG, quipazine) and antagonists (granisetron, palonosetron, tropisetron) yielded similar affinities in all three assays. When cysteine substitutions were introduced into the 5-HT3 receptor binding site the same changes in binding affinity were seen for both granisetron and the fluorescein-derivative, suggesting that they both adopt orientations that are consistent with co-crystal structures of granisetron with a homologous protein (5HTBP). As expected, in vivo live imaging in anaesthetized mice revealed staining in the abdominal cavity in intestines, but also in salivary glands. The unexpected presence of 5-HT3 receptors in mouse salivary glands was confirmed by Western blots. Overall, these results demonstrate the wide utility of our new high-affinity fluorescently-labeled 5-HT3 receptor probes, ranging from in vitro receptor pharmacology, including FC and FP ligand competition, to live imaging of 5-HT3 expressing tissues.
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We report the contrast formation in the local contact potential difference (LCPD) measured by Kelvin probe force microscopy (KPFM) on single charge-transfer complexes (CTCs) on a NaCl bilayer on Cu(111). At different tip heights, we found quantitatively different LCPD contrasts that characterize different properties of the molecule. In the small distance regime, the tip penetrates the electron density of the molecule, and the contrast is related to the size and topography of the electron shell of the molecule. For larger distances, the LCPD contrast corresponds to the electrostatic field above the molecule. However, in the medium-distance regime, that is, for tip heights similar to the size of the molecule, the nonspherical distribution of π- and σ-electrons often conceals the effect of the partial charges within the molecule. Only for large distances does the LCPD map converge toward the simple field of a dipole for a polar molecule.
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A tetrathiafulvalene (TTF)-fused piazselenole as a novel redox-active probe for highly sensitive determination of physiological thiols by electrochemical detection has been synthesised and successfully tested in intracellular non-protein thiol detection, reaching a detection limit of 10−10 M.
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The use of fluorescence is a valuable and increasingly accessible means of probing the pharmacology and physiology of cells and their receptors. To date, the use of fluorescence-based methods for 5-HT3 receptor research has been quite limited and, although a variety of approaches have been described, these are broadly distributed throughout the literature. In this review we condense these findings into a single, accessible source of reference with the hope of promoting the use of these valuable molecular probes.
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The adenosine receptors are members of the G-protein coupled receptor (GPCR) family which represents the largest class of cell-surface proteins mediating cellular communication. As a result, GPCRs are formidable drug targets and it is estimated that approximately 30% of the marketed drugs act through members of this receptor class. There are four known subtypes of adenosine receptors: A1, A2A, A2B and A3. The adenosine A1 receptor, which is the subject of this presentation, mediates the physiological effects of adenosine in various tissues including the brain, heart, kidney and adipocytes. In the brain for instance, its role in epilepsy and ischemia has been the focus of many studies. Previous attempts to study the biosynthesis, trafficking and agonist-induced internalisation of the adenosine A1 receptor in neurons using fluorescent protein-receptor fusion constructs have been hampered by the sheer size of the fluorescent protein (GFP) that ultimately affected the function of the receptor. We have therefore initiated a research programme to develop small molecule fluorescent agonists that selectively activate the adenosine A1 receptor. Our probe design is based on the endogenous ligand adenosine and the known unselective adenosine receptor agonist NECA. We have synthesised a small library of non-fluorescent adenosine derivatives that have different cyclic and bicyclic moieties at the 6 position of the purine ring and have evaluated the pharmacology of these compounds using a yeast-based assay. This analysis revealed compounds with interesting behaviour, i.e. exhibiting subtype-selectivity and biased signalling, that can be potentially used as tool compounds in their own right for cellular studies of the adenosine A1 receptor. Furthermore, we have also linked fluorescent dyes to the purine ring and discovered fluorescent compounds that can activate the adenosine A1 receptor.
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Neuropharmacology (Elsevier) Special Issue entitled "Fluorescent Tools in Neuropharmacology" includes ten contributions from key researchers in this field. These contributions comprise reviews and orginial research articles.
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We describe the main scientific goals to be addressed by future in situ exploration of Saturn.