A key goal of biology is to relate the expression of specific genes to a particular cellular phenotype. However, current assays for gene expression destroy the structural context. By combining advances in computational fluorescence microscopy with multiplex probe design, we devised technology in which the expression of many genes can be visualized simultaneously inside single cells with high spatial and temporal resolution. Analysis of 11 genes in serum-stimulated cultured cells revealed unique patterns of gene expression within individual cells. Using the nucleus as the substrate for parallel gene analysis, we provide a platform for the fusion of genomics and cell biology: "cellular genomics."

Early yearsThe broader historical setting for the development of cytochemical techniques in general is extensively and excellently reviewed elsewhere (van der Ploeg, 2000). We present a much-abridged history to describe the introduction, development and maturation of fluorescence in situ hybridization (FISH) specifically. In brief, the earliest histochemistry techniques consisted of the use of different sorts of natural and synthetic dyes to stain cellular structures and sub-cellular accumulations. These compounds were generally non-specific because they had affinities for certain general categories of molecules, be they basic proteins, nucleic acids, lipids or carbohydrates. Even the more specific stains for cellular accumulations and macromolecular complexes such as hemosiderin, amyloid, elastin and reticular fibers were not generally applicable to investigation of all the biomolecules of interest. The ability to detect specific molecular identities was first demonstrated using antigen-antibody interactions. Early in the 1940s, antibodies were conjugated to fluorochromes without loss of their epitope-binding specificity. Decades later, the first antibody-dependent fluorescent detection of nucleic acid hybrids was achieved (Rudkin and Stollar, 1977); however, this technology was soon replaced by the advent of fluorescent nucleic acid probes. The earliest in situ hybridizations, performed in the late 1960s, were not fluorescent at all, but rather utilized probes labeled with radioisotopes. Techniques not employing fluorescence, such as enzyme-based chromogenic reporters (reviewed by Hougaard et al., 1997) and gold-based probe systems used in electron microscopy (reviewed by Puvion-Dutilleul and Puvion, 1996) are each fields in their own right. Owing to space limitations,

Myocardial perfusion imaging and MSCT provide different and complementary information on CAD, namely, detection of atherosclerosis versus detection of ischemia. As compared to invasive angiography, MSCT has a high accuracy for detecting CAD in patients with an intermediate likelihood of CAD.

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Sigmoid volvulus has a spectrum of imaging findings. A classic appearance is absent on approximately one half of scanograms and one fourth of CT scans. Use of new signs that model the pathophysiologic characteristics of volvulus (X-marks-the-spot sign for more complete twisting and split-wall sign for less severe twisting) may improve diagnostic confidence.