Many genes and signalling pathways controlling cell proliferation, death and differentiation, as well as genomic integrity, are involved in cancer development. New techniques, such as serial analysis of gene expression and cDNA microarrays, have enabled measurement of the expression of thousands of genes in a single experiment, revealing many new, potentially important cancer genes. These genome screening tools can comprehensively survey one tumor at a time; however, analysis of hundreds of specimens from patients in different stages of disease is needed to establish the diagnostic, prognostic and therapeutic importance of each of the emerging cancer gene candidates. Here we have developed an array-based high-throughput technique that facilitates gene expression and copy number surveys of very large numbers of tumors. As many as 1000 cylindrical tissue biopsies from individual tumors can be distributed in a single tumor tissue microarray. Sections of the microarray provide targets for parallel in situ detection of DNA, RNA and protein targets in each specimen on the array, and consecutive sections allow the rapid analysis of hundreds of molecular markers in the same set of specimens. Our detection of six gene amplifications as well as p53 and estrogen receptor expression in breast cancer demonstrates the power of this technique for defining new subgroups of tumors.

A real-time ultrasonic imaging system has been developed to visualize dynamic motions of the tongue during continuous speech. Lingual motion configurations are displayed and recorded synchronously with the speech signal, time in milliseconds, and frontal and lateral views of the face during articulation. All data are videotaped and stored permanently for analysis. Data on the vertical movement of the tongue surface was obtained on 30 normal adult speakers. This technique seems to provide a useful, noninvasive technique for quantifying tongue position during speech utterances and possibly has potential as a clinical tool.

The implementation of muscle ergometry during magnetic resonance spectroscopy and imaging is complicated by the restrictive dimensions of the magnet bore and the presence of a strong static magnetic field. We have developed a dynamometer that is compatible with these constraints. This device can provide resistance to voluntary muscle contraction during isometric, isokinetic concentric, and isokinetic eccentric muscle contractions. While controlling muscle contraction speed, the dynamometer simultaneously records muscle torque production at a 10-Hz sampling frequency to allow assessment of compliance and retrospective normalization of power output for the mass of active muscle. All parameters relevant to muscle contraction are selectable, including percentage of maximal voluntary contraction, velocity of muscle contraction, duty cycle, and range of motion for the contraction. This paper provides examples of 31P-magnetic resonance spectroscopic measurements during isokinetic concentric contractions of the ankle dorsiflexors, isokinetic eccentric contractions of the soleus, and isometric contractions of the soleus. Operation of the dynamometer has no adverse effects on the integrity of the 31P-magnetic resonance spectra at 4 T, permitting temporal resolution of the phosphocreatine resynthesis rate of approximately 1 spectrum/s. The unique capabilities of this dynamometer will facilitate studies into the metabolic response of working muscle in healthy and diseased populations.

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