Mechanisms of reovirus-induced cell death and tissue injury: role of apoptosis and virus-induced perturbation of host-cell signaling and transcription factor activation.

Reoviruses have provided insight into the roles played by specific viral genes and the proteins they encode in virus-induced cell death and tissue injury. Apoptosis is a major mechanism of cell death induced by reoviruses. Reovirus-induced apoptosis involves both death-receptor and mitochondrial cell death pathways. Reovirus infection is associated with selective activation of mitogen activated protein kinase (MAPK) cascades including JNK/SAPK. Infection also perturbs transcription factor signaling resulting in the activation of c-Jun and initial activation followed by strain-specific inhibition of NF-kappaB. Infection results in changes in the expression of genes encoding proteins involved in cell cycle regulation, apoptosis, and DNA damage and repair processes. Apoptosis is a major mechanism of reovirus-induced injury to key target organs including the CNS and heart. Inhibition of apoptosis through the use of caspase or calpain inhibitors, minocycline, or in caspase 3(-/-) mice all reduce virus-associated tissue injury and enhance survival of infected animals. Reoviruses induce apoptotic cell death (oncolysis) in a wide variety of cancer cells and tumors. The capacity of reoviruses to grow efficiently in transformed cells is enhanced by the presence of an activated Ras signaling pathway likely through mechanisms involving inhibition of antiviral PKR signaling and activation of Ras/RalGEF/p38 pathways. The potential of reovirus-induced oncolysis in therapy of human cancers is currently being investigated in phase I/II clinical trials.

Characterization of an absolute cryogenic radiometer as a standard detector for radiant-power measurements.

An active cavity radiometer of the electrical substitution type with a cone receiver that operates at 2-4 K has been developed for measuring radiant fluxes in the dynamic range of 20 nW to 100 microW within an uncertainty of +/-1% (2sigmalevel). It is a broadband absolute detector with a flat overall absorption efficiency that is >99% for radiation from the visible to long-wavelength IR. The system is designed based on thermal modeling and experimental measurements of concepts. It has been installed in the cryogenic chamber for low-background infrared radiation calibrations at the National Institute of Standards and Technology (NIST) for testing cryogenic blackbody sources, detectors, and optical components. Its time constant, responsivity, and nonequivalence error have been measured. They are in agreement with design predictions. Radiant power measurements of an amplitude-stabilized He-Ne laser beam with the radiometer and an industry standard photodiode detector, QED-200, have been intercompared and found to be in agreement. The intercomparison ratio of the measurements with the absolute cryogenic radiometer and QED-200 was 1.004 in the 75-100-microW range with an uncertainty of 0.5% (the 3sigma level).

Remote biomedical spectroscopic imaging of human artery wall.

We discuss a general technique, laser spectroscopic imaging (LSI), remote acquisition of spectroscopic images of biological tissues and tissue conditions. The technique employs laser-induced spectroscopic signals, collected and transmitted via an array of optical fibers, to produce discrete pixels of information from which a map or image of a desired tissue characteristic is constructed. We describe a prototype LSI catheter that produces spectral images of the interior of human arteries for diagnosis of atherosclerosis. The diagnostic is based on the fact that normal artery wall and atherosclerotic plaque exhibit distinct fluorescence spectra in the 500-650 nm range when excited by 476-nm laser light; the fluorescence from blood is minimal. The catheter is composed of 19 optical fibers enclosed in a transparent, protective shield. Argon ion laser radiation is used for excitation, and an optical multichannel spectral analyzer is used for detection. Sequential sampling is used to minimize crosstalk among fibers and reduce blurring of the image. Computer-processed 19-pixel spectroscopic images are produced of fresh cadaver artery in vitro. Regions of normal tissue, plaque, and blood are identified, and the diagnoses are confirmed histologically and by direct spatial correlation. The results demonstrate the concept of using this laser catheter system for real-time imaging.