MALDI imaging mass spectrometry reveals COX7A2, TAGLN2 and S100-A10 as novel prognostic markers in Barrett's adenocarcinoma

To characterize proteomic changes found in Barrett's adenocarcinoma and its premalignant stages, the proteomic profiles of histologically defined precursor and invasive carcinoma lesions were analyzed by MALDI imaging MS. For a primary proteomic screening, a discovery cohort of 38 fresh frozen Barrett's adenocarcinoma patient tissue samples was used. The goal was to find proteins that might be used as markers for monitoring cancer development as well as for predicting regional lymph node metastasis and disease outcome. Using mass spectrometry for protein identification and validating the results by immunohistochemistry on an independent validation set, we could identify two of 60 differentially expressed m/z species between Barrett's adenocarcinoma and the precursor lesion: COX7A2 and S100-A10. Furthermore, among 22 m/z species that are differentially expressed in Barrett's adenocarcinoma cases with and without regional lymph node metastasis, one was identified as TAGLN2. In the validation set, we found a correlation of the expression levels of COX7A2 and TAGLN2 with a poor prognosis while S100-A10 was confirmed by multivariate analysis as a novel independent prognostic factor in Barrett's adenocarcinoma. Our results underscore the high potential of MALDI imaging for revealing new biologically significant molecular details from cancer tissues which might have potential for clinical application. This article is part of a Special Issue entitled: Translational Proteomics.

MR motility imaging in Crohn's disease improves lesion detection compared with standard MR imaging

To evaluate retrospectively in patients with Crohn's disease (CD) if magnetic resonance (MR) motility alterations correlate with CD typical lesions leading to an increased detection rate.

Focal cystic high-attenuation lesions: characterization in renal phantom by using photon-counting spectral CT--improved differentiation of lesion composition

To evaluate the capability of spectral computed tomography (CT) to improve the characterization of cystic high-attenuation lesions in a renal phantom and to test the hypothesis that spectral CT will improve the differentiation of cystic renal lesions with high protein content and those that have undergone hemorrhage or malignant contrast-enhancing transformation.

The outcome of bifurcation lesion stenting using a biolimus-eluting stent with a bio-degradable polymer compared to a sirolimus-eluting stent with a durable polymer

This study investigated the differences in clinical outcomes between patients with bifurcation lesions (BL) treated with a biolimus-eluting stent (BES) with a biodegradable polymer, and a sirolimus-eluting stent (SES) with a durable polymer.

Distribution of amyloid precursor protein and amyloid-beta in ocular hypertensive C57BL/6 mouse eyes

Amyloid precursor protein (APP) and amyloid-beta (Abeta) appear to participate in the pathophysiology of retinal ganglion cell (RGC) death in glaucoma. We, therefore, determined the distribution of APP and Abeta in the retinas of C57BL/6 mice after induction of chronic ocular hypertension.

Evaluation of perpendicular reflection intensity for assessment of caries lesion activity/inactivity

The aim of this study was to evaluate, using visual assessment, an experimental optical sensor measuring perpendicular reflection intensity (PRI) as an indicator of enamel caries lesion activity/inactivity. Forty teeth with either an active or an inactive enamel lesion were selected from a pool of extracted teeth. Each tooth was cut into halves, with a clinically sound half and a half with a non-cavitated enamel lesion. After gentle plaque removal, the teeth were kept moistened. The lesions were then photographed and a defined measuring site per lesion was chosen and indicated with an arrow on a printout. Independently, the chosen site was visually assessed for lesion activity, and its glossiness was measured with PRI assessment. Surface roughness (SR) was assessed with optical profilometry using a confocal microscope. Visual assessment and PRI were repeated after several weeks and a reliability analysis was performed. For enamel lesions visually scored as active versus inactive, significantly different values were obtained with both PRI and SR. PRI values of the clinically sound control surfaces were significantly different only from active lesions. Generally, inactive lesions had the same glossiness and the same roughness as the sound control surfaces. The reliabilities for visual assessment (? = 0.89) and for PRI (ICC = 0.86) were high. It is concluded that, within the limits of this study, PRI can be regarded as a promising tool for quantitative enamel lesion activity assessment. There is scope and potential for the PRI device to be considerably improved for in vivo use.

Blue Light versus Green Light Autofluorescence: Lesion Size of Areas with Geographic Atrophy

Blue-light fundus autofluorescence (FAF) imaging is currently widely used for assessing dry age-related macular degeneration (ARMD). However, at this wavelength, the fovea appears as circular zone of marked hypofluorescence, due to the absorption of macular pigment (MP). This dark spot could be misinterpreted as an atrophic area and could lead to difficulties in identifying small, central changes. The purpose of the study was to analyze differences in image quality, FAF patterns, and lesion size, when using conventional blue-light (Λ(1) = 488 nm) and green-light (Λ(2) = 514 nm) FAF.

Gender is an independent risk factor for distribution pattern and lesion morphology in chronic critical limb ischemia

The aim of this study was to determine gender differences in atherosclerotic lesion morphology and distribution pattern of patients with critical limb ischemia (CLI).

Segmentation of brain tumor images based on atlas-registration combined with a Markov-Random-Field lesion growth model

We present an automatic method to segment brain tissues from volumetric MRI brain tumor images. The method is based on non-rigid registration of an average atlas in combination with a biomechanically justified tumor growth model to simulate soft-tissue deformations caused by the tumor mass-effect. The tumor growth model, which is formulated as a mesh-free Markov Random Field energy minimization problem, ensures correspondence between the atlas and the patient image, prior to the registration step. The method is non-parametric, simple and fast compared to other approaches while maintaining similar accuracy. It has been evaluated qualitatively and quantitatively with promising results on eight datasets comprising simulated images and real patient data.

Expression of the nociceptin precursor and nociceptin receptor is modulated in cancer and septic patients

A role of nociceptin and its receptor (NOP) in pain and immune function has been suggested. The hypothesis was that mRNA expression of NOP and the nociceptin precursor pre-pronociceptin (pN/OFQ) in peripheral blood cells differs in end-stage cancer patients suffering from chronic pain and septic intensive care unit (ICU) patients compared with healthy controls.

Neuronal precursor cell-expressed developmentally down-regulated 4-1 (NEDD4-1) controls the sorting of newly synthesized Ca(V)1.2 calcium channels

Neuronal precursor cell-expressed developmentally down-regulated 4 (Nedd4) proteins are ubiquitin ligases, which attach ubiquitin moieties to their target proteins, a post-translational modification that is most commonly associated with protein degradation. Nedd4 ubiquitin ligases have been shown to down-regulate both potassium and sodium channels. In this study, we investigated whether Nedd4 ubiquitin ligases also regulate Ca(v) calcium channels. We expressed three Nedd4 family members, Nedd4-1, Nedd4-2, and WWP2, together with Ca(v)1.2 channels in tsA-201 cells. We found that Nedd4-1 dramatically decreased Ca(v) whole-cell currents, whereas Nedd4-2 and WWP2 failed to regulate the current. Surface biotinylation assays revealed that Nedd4-1 decreased the number of channels inserted at the plasma membrane. Western blots also showed a concomitant decrease in the total expression of the channels. Surprisingly, however, neither the Ca(v) pore-forming α1 subunit nor the associated Ca(v)β and Ca(v)α(2)δ subunits were ubiquitylated by Nedd4-1. The proteasome inhibitor MG132 prevented the degradation of Ca(v) channels, whereas monodansylcadaverine and chloroquine partially antagonized the Nedd4-1-induced regulation of Ca(v) currents. Remarkably, the effect of Nedd4-1 was fully prevented by brefeldin A. These data suggest that Nedd4-1 promotes the sorting of newly synthesized Ca(v) channels for degradation by both the proteasome and the lysosome. Most importantly, Nedd4-1-induced regulation required the co-expression of Ca(v)β subunits, known to antagonize the retention of the channels in the endoplasmic reticulum. Altogether, our results suggest that Nedd4-1 interferes with the chaperon role of Ca(v)β at the endoplasmic reticulum/Golgi level to prevent the delivery of Ca(v) channels at the plasma membrane.

Risk of target lesion failure in relationship to vessel angiographic geometry and stent conformability using the second generation of drug-eluting stents

Vessel angulation and large changes in vessel geometry after stent implantation have been associated with an increased risk of target lesion failure (TLF) using bare-metal stents. Second-generation drug-eluting stents (DES)offer superior conformability and inhibition of neointima. The aim of the study is to investigate the relationship between pre and post-implant vessel geometry and the occurrence of TLF at 1 year after treatment with second-generation DES; and to compare the conformability of Resolute and Xience stents.