Positron emission tomography was used to measure cerebral activity and to evaluate regional interrelationships within visual cortices and their projections during rapid eye movement (REM) sleep in human subjects. REM sleep was associated with selective activation of extrastriate visual cortices, particularly within the ventral processing stream, and an unexpected attenuation of activity in the primary visual cortex; increases in regional cerebral blood flow in extrastriate areas were significantly correlated with decreases in the striate cortex. Extrastriate activity was also associated with concomitant activation of limbic and paralimbic regions, but with a marked reduction of activity in frontal association areas including lateral orbital and dorsolateral prefrontal cortices. This pattern suggests a model for brain mechanisms subserving REM sleep where visual association cortices and their paralimbic projections may operate as a closed system dissociated from the regions at either end of the visual hierarchy that mediate interactions with the external world.

These data suggest a role for SSAT, the rate-limiting enzyme in the catabolism of polyamines, in suicide and depression and a role for the SSAT342 locus in the regulation of SSAT gene expression.

Chromosome rearrangement, a hallmark of cancer, has profound effects on carcinogenesis and tumor phenotype. We used a panel of 60 human cancer cell lines (the NCI-60) as a model system to identify relationships among DNA copy number, mRNA expression level, and drug sensitivity. For each of 64 cancer-relevant genes, we calculated all 4,096 possible Pearson's correlation coefficients relating DNA copy number (assessed by comparative genomic hybridization using bacterial artificial chromosome microarrays) and mRNA expression level (determined using both cDNA and Affymetrix oligonucleotide microarrays). The analysis identified an association of ERBB2 overexpression with 3p copy number, a finding supported by data from human tumors and a mouse model of ERBB2-induced carcinogenesis. When we examined the correlation between DNA copy number for all 353 unique loci on the bacterial artificial chromosome microarray and drug sensitivity for 118 drugs with putatively known mechanisms of action, we found a striking negative correlation (À0.983; 95% bootstrap confidence interval, À0.999 to À0.899) between activity of the enzyme drug L-asparaginase and DNA copy number of genes near asparagine synthetase in the ovarian cancer cells. Previous analysis of drug sensitivity and mRNA expression had suggested an inverse relationship between mRNA levels of asparagine synthetase and L-asparaginase sensitivity in the NCI-60. The concordance of pharmacogenomic findings at the DNA and mRNA levels strongly suggests further study of L-asparaginase for possible treatment of a low-synthetase subset of clinical ovarian cancers. The DNA copy number database presented here will enable other investigators to explore DNA transcript-drug relationships in their own domains of research focus. [Mol Cancer Ther 2006;5(4):853 -67]

No abstract

The Coping Strategies Questionnaire (CSQ) (Rosenstiel and Keefe 1983) is the most widely used measure of pain coping strategies. To date, with one exception (Tuttle et al. 1991), studies examining the factor structure of the CSQ have used the composite scores of its 8 a-priori theoretically derived scales rather than the 48 individual items. An examination of the match between the 8 theoretically derived scales and scales empirically extracted from an item analysis is lacking. Accordingly, the CSQ was administered to 126 chronic pain (whiplash) patients. Factor analyses of the individual items revealed an 8-factor structure to be uninterpretable. Of the 2-9-factor solutions tested, the 5-factor structure was the most interpretable: Factor 1, Distraction; Factor 2, Ignoring Pain Sensations; Factor 3, Reinterpreting Pain Sensations; Factor 4, Catastrophizing; Factor 5, Praying and Hoping. Eighteen Ph.D. or M.D. level clinicians classified items into their corresponding category with a high degree of accuracy (on average, 90.2%), attesting to the face and construct validity of the subscales. Four subscales, Catastrophizing, Reinterpreting Pain Sensations, Praying and Hoping and (to a lesser degree) Ignoring Pain Sensations, correspond with parallel subscales proposed by Rosensteil and Keefe (1983). The fifth subscale, Distraction, is comprised of items from their Diverting Attention and Increasing Activity Level subscales, suggesting that cognitive and behavioural distraction comprise 1 rather than 2 coping strategies. That CSQ items on the original Coping Self-Statements and the Increasing Pain Behaviour subscales failed to load consistently on any factor suggests that they do not reliably measure distinct coping strategies.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparing cDNA and oligonucleotide array data: concordance of gene expression across platforms for the NCI-60 cancer cells Microarray gene-expression profiles are generally validated one gene at a time by real-time RT-PCR. We describe here a different approach based on simultaneous mutual validation of large numbers of genes using two different expression-profiling platforms. The result described here for the NCI-60 cancer cell lines is a consensus set of genes that give similar profiles on spotted cDNA arrays and Affymetrix oligonucleotide chips. Global concordance is parameterized by a 'correlation of correlations' coefficient. AbstractMicroarray gene-expression profiles are generally validated one gene at a time by real-time RT-PCR. We describe here a different approach based on simultaneous mutual validation of large numbers of genes using two different expression-profiling platforms. The result described here for the NCI-60 cancer cell lines is a consensus set of genes that give similar profiles on spotted cDNA arrays and Affymetrix oligonucleotide chips. Global concordance is parameterized by a 'correlation of correlations' coefficient.

No abstract

Several lines of evidence support the idea that individuals who commit suicide have a certain biological predisposition, part of which is given by genes. Studies investigating genetic factors increasing suicide predisposition have been limited by current knowledge of the suicide neurobiology and have typically investigated one or a few genes at a time, whereas it is anticipated that several genes account for the total genetic variance mediating suicide. This review focuses on the advantages and the interest of using the microarray technology to investigate the neurobiology of suicide and discusses, by means of a data analysis example, the possible methodological problems and bioinformatic strategies that should be employed in order to separate the signal from the large amount of background noise, which is usually generated in such studies. Microarray expression studies and related platforms are promising tools to gain better insight into the neurobiology of suicide.