Usefulness of quantitative echocardiographic techniques to predict recovery of regional and global left ventricular function after acute myocardial infarction

The left ventricular response to dobutamine may be quantified using tissue Doppler measurement of myocardial velocity or displacement or 3-dimensional echocardiography to measure ventricular volume and ejection fraction. This study sought to explore the accuracy of these methods for predicting segmental and global responses to therapy. Standard dobutamine and 3-dimensional echocardiography were performed in 92 consecutive patients with abnormal left ventricular function at rest. Recovery of function was defined by comparison with follow-up echocardiography at rest 5 months later. Segments that showed improved regional function at follow-up showed a higher increment in peak tissue Doppler velocity with dobutamine therapy than in nonviable segments (1.2 +/- 0.4 vs 0.3 +/- 0.2 cm/s, p = 0.001). Similarly, patients who showed a > 5% improvement of ejection fraction at follow-up showed a greater displacement response to dobutamine (6.9 +/- 3.2 vs 2.1 +/- 2.3 mm, p = 0.001), as well as a higher rate of ejection fraction, response to dobutamine (9 +/- 3% vs 2 +/- 2%, p = 0.001). The optimal cutoff values for predicting subsequent recovery of function at rest were an increment of peak velocity > 1 cm/s, >5 mm of displacement, and a >5% improvement of ejection fraction with low-dose dobutamine. (C) 2003 by Excerpta Medica, Inc.

The AF-1 Domain of the Orphan Nuclear Receptor NOR-1 Mediates Trans-activation, Coactivator Recruitment, and Activation by the Purine Anti-metabolite 6-Mercaptopurine

NOR-1/NR4A3 is an orphan member of the nuclear hormone receptor superfamily. NOR-1 and its close relatives Nurr1 and Nur77 are members of the NR4A subgroup of nuclear receptors. Members of the NR4A subgroup are induced through multiple signal transduction pathways. They have been implicated in cell proliferation, differentiation, T-cell apoptosis, chondrosarcomas, neurological disorders, inflammation, and atherogenesis. However, the mechanism of transcriptional activation, coactivator recruitment, and agonist-mediated activation remain obscure. Hence, we examined the molecular basis of NOR-1-mediated activation. We observed that NOR-1 trans-activates gene expression in a cell- and target-specific manner; moreover, it operates in an activation function (AF)-1-dependent manner. The N-terminal AF-1 domain delimited to between amino acids 1 and 112, preferentially recruits the steroid receptor coactivator (SRC). Furthermore, SRC-2 modulates the activity of the AF-1 domain but not the C-terminal ligand binding domain (LBD). Homology modeling indicated that the NOR-1 LBD was substantially different from that of hRORbeta, a closely related AF-2-dependent receptor. In particular, the hydrophobic cleft characteristic of nuclear receptors was replaced with a very hydrophilic surface with a distinct topology. This observation may account for the inability of this nuclear receptor LBD to efficiently mediate cofactor recruitment and transcriptional activation. In contrast, the N-terminal AF-1 is necessary for cofactor recruitment and can independently conscript coactivators. Finally, we demonstrate that the purine anti-metabolite 6-mercaptopurine, a widely used antineoplastic and anti-inflammatory drug, activates NOR-1 in an AF-1-dependent manner. Additional 6-mercaptopurine analogs all efficiently activated NOR-1, suggesting that the signaling pathways that modulate proliferation via inhibition of de novo purine and/or nucleic acid biosynthesis are involved in the regulation NR4A activity. We hypothesize that the NR4A subgroup mediates the genotoxic stress response and suggest that this subgroup may function as sensors that respond to genotoxicity.

Resolution enhancement by subtraction of confocal signals taken at different pinhole sizes

Subtractive imaging in confocal fluorescence light microscopy is based on the subtraction of a suitably weighted widefield image from a confocal image. An approximation to a widefield image can be obtained by detection with an opened confocal pinhole. The subtraction of images enhances the resolution in-plane as well as along the optic axis. Due to the linearity of the approach, the effect of subtractive imaging in Fourier-space corresponds to a reduction of low spatial frequency contributions leading to a relative enhancement of the high frequencies. Along the direction of the optic axis this also results in an improved sectioning. Image processing can achieve a similar effect. However, a 3D volume dataset must be acquired and processed, yielding a result essentially identical to subtractive imaging but superior in signal-to-noise ratio. The latter can be increased further with the technique of weighted averaging in Fourier-space. A comparison of 2D and 3D experimental data analysed with subtractive imaging, the equivalent Fourier-space processing of the confocal data only, and Fourier-space weighted averaging is presented. (C) 2003 Elsevier Ltd. All rights reserved.

Simultaneous observations of ionospheric quasiperiodic scintillations from short and long meridional baselines using VHF transmissions from transit satellites

For the first time it was possible to observe regular quasiperiodic scintillations (QPS) in VHF radio-satellite transmissions from orbiting satellites simultaneously at short (2.1 km) and long (121 km) meridional baselines in the vicinity of a typical mid-latitude station (Brisbane; 27.5degreesS and 152.9degreesE geog. and 35.6degrees invar.lat.), using three sites (St. Lucia-S, Taringa-T in Brisbane and Boreen Pt.-B, north of Brisbane). A few pronounced quasiperiodic (QP) events were recorded showing unambiguous regular structures at the sites which made it possible to deduce a time displacement of the regular fading minimum at S, T and B. The QP structure is highly dependent on the geometry of the ray-path from a satellite to the observer which is manifested as a change of a QP event from symmetrical to non-symmetrical for stations separated by 2.1 km, and to a radical change in the structure of the event over a distance of 121 km. It is suggested the short-duration intense QP events are due to a Fresnel diffraction (or a reflection mechanism) of radio-satellite signals by a single ionospheric irregularity in a form of an ellipsoid with a large ionization gradient along the major axis. The structure of a QP event depends on the angle of viewing of the irregular blob from a radio-satellite. In view of this it is suggested that the reported variety of the ionization formation, responsible for different types of QPS, is only apparent but not real. (C) 2003 Elsevier Science Ltd. All rights reserved.