Autofluorescence-Free Live-Cell Imaging Using Terbium Nanoparticles.

Fluorescent nanoparticles (NPs) have become irreplaceable tools for advanced cellular and subcellular imaging. While very bright NPs require excitation with UV or visible light, which can create strong autofluorescence of biological components, NIR-excitable NPs without autofluorescence issues exhibit much lower brightness. Here, we show the application of a new type of surface-photosensitized terbium NPs (Tb-NPs) for autofluorescence-free intracellular imaging in live HeLa cells. The combination of exceptionally high brightness, high photostability, and long photoluminecence (PL) lifetimes for highly efficient suppression of the short-lived autofluorescence allowed for time-gated PL imaging of intracellular vesicles over 72 h without toxicity and at extremely low Tb-NP concentrations down to 12 pM. Detection of highly resolved long-lifetime (ms) PL decay curves from small (∼10 µm2) areas within single cells within a few seconds emphasized the unprecedented photophysical properties of Tb-NPs for live-cell imaging that extend well beyond currently available nanometric imaging agents.

Correlation of hormone receptor status between circulating tumor cells, primary tumor, and metastasis in breast cancer patients

Purpose. Estrogen receptor (ER) and progesterone receptor (PR) status is prognostic and predictive in breast cancer. Because metastatic breast tumor biopsies are not routinely feasible, circulating tumor cells (CTCs) offer an alternative source of determining ER/PR tumor status. Methods/patients. Peripheral blood was collected prospectively from 36 patients with metastatic breast cancer. CTCs were isolated using the microfluidic OncoCEE™ platform. Detection was accomplished with an expanded anti-cytokeratin (CK) cocktail mixture and anti-CD45. ER/PR protein expression was assessed by immunocytochemistry (ICC) on the CK+ cells and compared to the primary and/or metastatic tumor by immunohistochemistry (IHC). Results. Among the 24 CK + CTC cases, a concordance of 68 % (15/22) in ER/PR status between primary breast tumor and CTCs and 83 % (10/12) between metastatic tumor and CTCs was observed. An overall concordance of 79 % (19/24) was achieved when assessing CTC and metastatic tumor (primary tumor substituted if metastatic breast biopsy not available). A test sensitivity of 72 % and specificity of 100 % was identified when comparing CTCs to tumor tissue. Of the 7 discordant cases between CTCs and primary tumor tissue, 2 were concordant with the metastatic biopsy. Conclusions. CTC ER/PR status using the OncoCEE™ platform is feasible, with high concordance in ER/PR status between tumor tissue (IHC) and CTCs (ICC). The prognostic and predictive significance of CTC ER/PR protein expression needs further evaluation in larger trials (AU)

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A strong two-photon induced phosphorescent Golgi-specific in vitro marker based on a heteroleptic iridium complex.

A new heteroleptic iridium complex demonstrated low cytotoxicity and near-infrared excitation (via two-photon absorption) for target-specific in vitro Golgi imaging in various cell lines (HeLa and A549 cells) with two-photon absorption cross section (~350 GM) in DMSO.

5-(Dimethylamino)-N-(4-ethynylphenyl)-1-naphthalenesulfonamide as a novel bifunctional antitumor agent and two-photon induced bio-imaging probe.

A novel compound, (5-(dimethylamino)-N-(4-ethynylphenyl)-1-naphthalenesulfonamide), was prepared and characterized; it shows dual functional roles as an effective antitumor and a two-photon induced bio-imaging agent.

The CD14(+/low)CD16(+) monocyte subset is more susceptible to spontaneous and oxidant-induced apoptosis than the CD14(+)CD16(-) subset.

Human monocytes can be classified into two subsets with distinctive characteristics. In this study, we report a difference in apoptotic potential between these two subsets with CD14(+/low)CD16(+) monocytes being more susceptible than CD14(+)CD16(-) monocytes to undergo spontaneous apoptosis and apoptosis induced by reactive oxygen species (ROS). By global transcriptomic and proteomic approaches, we observed that CD14(+/low)CD16(+) monocytes expressed higher levels of pro-apoptotic genes and proteins such as TNFα, caspase 3, Bax and cytochrome c and showed more caspases 3 and 7 activities. They also exhibited greater aerobic respiration resulting in a higher production of ROS from the mitochondria. CD14(+)CD16(-) monocytes, in contrast, showed higher expression of glutathione (GSH)-metabolizing genes such as GSH peroxidase and microsomal GSH S-transferase and were more resistant to oxidative stress than CD14(+/low)CD16(+) monocytes. The apoptosis of CD14(+/low)CD16(+) monocytes was ROS dependent as reducing ROS levels significantly reduced cell death. This is the first report of a differential apoptotic propensity of human monocyte subsets, and gaining a better understanding of this process may help to provide a better understanding of the roles of these subsets during homeostasis and under pathological conditions, particularly in situations in which high levels of oxidants are present.

Cardiac resynchronization: a novel therapy for heart failure.

Despite advances in medical therapy for patients with congestive heart failure, morbidity and mortality remain high. Conduction abnormalities, such as left bundle branch block, right bundle branch block, and nonspecific conduction delay, are observed commonly in patients with dilated cardiomyopathy. In patients with heart failure, the presence of intraventricular conduction delay is associated with more severe mitral regurgitation and worsened left ventricular systolic and diastolic function, and is an independent risk factor for increased mortality. Conventional dual-chamber (right atrial and right ventricular) pacing with a short atrioventricular delay was initially introduced as therapy for patients with advanced congestive heart failure to improve diastolic dysfunction and reduce mitral regurgitation. The acute beneficial hemodynamic effects observed in early, uncontrolled studies were not confirmed in subsequent randomized, controlled studies with longer follow-up. Cardiac resynchronization with novel biventricular (left and right ventricular) pacing systems has resulted in hemodynamic and functional benefits in patients with congestive heart failure and an underlying intraventricular conduction delay. Improvements in cardiac index, systolic blood pressure, and functional class have been reported with biventricular pacing, both acutely and at more than 1 year of follow-up. These encouraging preliminary results with biventricular pacing in patients with congestive heart failure will be validated in two prospective, randomized, controlled trials, Multicenter InSync Randomized Clinical Evaluation (MIRACLE) and Comparison of Medical Therapy, Pacing, and Defibrillation in Chronic Heart Failure (COMPANION). These studies are designed to evaluate the long-term efficacy of biventricular pacing in improving exercise capacity and in reducing morbidity and mortality in patients with advanced, symptomatic congestive heart failure. (c)2001 by CHF, Inc.

Ionization processes and charge-state distribution in a highly ionized high- Z laser-produced plasma

The charge-state distribution in a well-characterized highly ionized Au plasma was accurately determined using time-resolved x-ray spectroscopy. Simultaneous measurements of the electron temperature and density allow the first direct comparisons with nonlocal thermodynamic equilibrium model predictions for the charge-state distribution of a highly ionized high- Z plasma in a nonradiative environment. The importance of two-electron atomic processes is clearly demonstrated.

Internal kink instability during off-axis electron cyclotron current drive in the DIII-D tokamak

Experimental evidence is reported of an internal kink instability driven by a new mechanism: barely trapped suprathermal electrons produced by off-axis electron cyclotron heating on the DIII-D tokamak. It occurs in plasmas with an evolving safety factor profile q(r) when q(min) approaches 1. This instability is most active when ECCD is applied on the high field side of the flux surface. It has a bursting behavior with poloidal/toroidal mode number = m/n = 1/1. In positive magnetic shear plasmas, this mode becomes the fishbone instability. This observation can be qualitatively explained by the drift reversal of the barely trapped suprathermal electrons.