Cocaine interacts with the novelty-seeking trait to modulate FGFR1 gene expression in the rat

The present study sought to determine the interaction between the novelty-seeking trait and cocaine treatment on gene expression in the fibroblast growth factor (FGF) system. Specifically, we assessed the regulation of FGFR1 in response to cocaine in animals that were selectively bred on the basis of their locomotor response to a novel environment. High-responder (HR) rats are those that exhibit increased locomotor response and exploratory behavior in a novel environment and low-responder (LR) rats are those that exhibit lower levels of exploratory behavior and are less active. Both phenotypes received daily injections of either cocaine (15 mg/kg, i.p.) or saline for 7 consecutive days. Animals were sacrificed 45 min following their last injection and FGFR1 gene expression was assessed in the hippocampus and prefrontal cortex by mRNA in situ hybridization. HR-bred rats exhibited increased FGFR1 mRNA in the hippocampus compared to LR-bred rats. Furthermore, cocaine decreased FGFR1 mRNA in the hippocampus and increased FGFR1 mRNA in the prefrontal cortex. Finally, HR and LR rats differed in their response to cocaine between brain regions. In the hippocampus, cocaine decreased gene expression in HR-bred rats without affecting LR-bred rats, whereas in the prefrontal cortex cocaine increased gene expression in LR-bred rats without affecting HR-bred rats. These results suggest that cocaine interacts with the novelty-seeking trait to alter gene expression. Thus, the FGF system may contribute to individual differences in the response to drugs of abuse.     

Microarray technology: a review of new strategies to discover candidate vulnerability genes in psychiatric disorders

OBJECTIVE: An international effort is in progress to discover candidate genes and pathways associated with psychiatric disorders, including two of the most serious diseases, schizophrenia and mood disorders, through the use of new technology-microarrays. Instead of studying one gene at a time, microarrays provide the opportunity to analyze thousands of genes at once. METHOD: This article reviews the steps in this discovery process, including the acquisition and characterization of high-quality postmortem brain tissue, RNA extraction, and preparation and use of microarray technology. Two alternative microarray methods and factors affecting the quality of array data are reviewed. RESULTS: New analytical strategies are being developed to process the massive data sets generated by microarray studies and to define the significance of implicated genes. Array results must be validated by other methods, including in situ hybridization and real-time polymerase chain reaction. Identified genes can also be evaluated in terms of their chromosomal locations and possible overlap with regions of suggestive linkage or association identified with genome-wide linkage analysis in psychiatry and in terms of overlap with genes identified by microarray studies in animals administered psychoactive drugs. Microarray studies are only the first major step in the process. Further efforts in the investigation involve multiple strategies for studying function and gene structure, including transgenic and knockout animal studies. CONCLUSIONS: Microarrays present a methodology that can identify genes or pathways for new and unique potential drug targets, determine premorbid diagnosis, predict drug responsiveness for individual patients, and, eventually, initiate gene therapy and prevention strategies.     

Correlation of estrogen beta-receptor messenger RNA with endogenous levels of plasma estradiol and progesterone in the female rat hypothalamus,the bed nucleus of stria terminalis and the medial amygdala

Estrogen receptor beta (ERbeta) has been previously mapped in the rat central nervous system. This study aims to explore the regulation of ERbeta mRNA as it is expressed in the intact and cycling female rat brain. Young adult female rats (90+ day, N=20) were screened for estrous phases via vaginal cytology and sacrificed. Brains and blood were collected and processed for in situ hybridization and estradiol (E2) and progesterone (P4) hormone assays, respectively. ERbeta mRNA levels exhibited significant correlations with ovarian steroid ratios (E2/P4) in various brain regions, including the bed nucleus of stria terminalis, the medial nucleus of amygdala, and the anteroventral periventricular nuclei but not the paraventricular and the supraoptic nuclei or the preoptic area of the hypothalamus. No regulatory changes were detected in the cortex. Specifically, in the affected regions, higher P4 levels were significantly correlated with higher ERbeta mRNA expression. In contrast, there was a tendency for higher E2 levels to be correlated with lower ERbeta mRNA expression, but this tendency reached significance only in the bed nucleus of stria terminalis. These results suggest that ERbeta mRNA is regulated in the intact and cycling female rat hypothalamic as well as extrahypothalamic brain regions, and the circulating ovarian hormones play a critical role.     

How good is the ACR accreditation phantom for assessing image quality in digital mammography?

RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate the American College of Radiology (ACR) accreditation phantom for assessing image quality in digital mammography. MATERIALS AND METHODS: Digital images were obtained of an ACR accreditation phantom at varying mAs (constant kVp) and varying kVp (constant mAs). The average glandular dose for a breast with 50% glandularity was determined for each technique factor. Images were displayed on a 5 mega-pixel monitor, with the window width and level settings individually optimized for viewing the fibers, specks, and masses in the ACR phantom. Digital images of the ACR phantom were presented in a random manner to eight observers, each of whom indicated the number of objects visible in each image. RESULTS: Intraobserver variability was greater than interobserver variability for the detection of fibers and specks, but the reverse was true for the detection of masses. As the mAs increased, the number of fibers visible increased from less than one at 5 mAs to all six being visible at 80 mAs. The corresponding number of visible specks increased from 12 to 24, and the number of visible masses increased from 1.25 to about four. Above 26 kVp, object visibility was constant with increasing x-ray tube voltage. Reducing the x-ray tube voltage to 24 kVp, however, reduced the number of visible fibers from six to five, the number of visible specks from 24 to 21.1, and the number of visible masses from four to 3.1. Observer performance was approximately constant for average glandular doses greater than 1.6 mGy, so that the range of lesion detectability in the ACR phantom occurs at doses lower than those normally encountered in clinical practice. CONCLUSION: The current design of the ACR phantom is unsatisfactory for assessing image quality in digital mammography.     

Technique factors and image quality as functions of patient weight at abdominal CT

PURPOSE: To investigate how changes in kilovolt peak and milliampere second settings, and patient weight affect transmitted x-ray energy fluence and the image contrast-to-noise ratio (CNR) at abdominal computed tomography (CT). MATERIALS AND METHODS: Cylinders of water were used as patient models, and x-ray spectra, including x-ray tube potentials of 80-140 kVp, were investigated. The mean photon energy and energy fluence transmitted through water cylinders with varying diameters and the image contrast for fat, muscle, bone, and iodine relative to water were determined. The effect of changing the x-ray tube potential on CNR also was investigated. RESULTS: At a constant kVp, increasing patient weight from 10 kg to 120 kg reduced the transmitted energy fluence by two orders of magnitude. Changing the x-ray tube potential from 80 kVp to 140 kVp increased the mean photon energy from approximately 52 keV to approximately 72 keV and thus reduced the image contrast relative to water by 12% for muscle, 21% for fat, 39% for bone, and 50% for iodine (approximate reduction values). Increasing the x-ray tube potential from 80 kVp to 140 kVp increased the CNR by a factor of 2.6 for muscle and by a factor of 1. 4 for iodine. CONCLUSION: With changes in patient weight at abdominal CT, x-ray tube potentials must be varied to maintain a constant detector energy fluence. Increasing the x-ray tube potential generally improves CNR.     

Mammographic image processing using wavelet processing techniques

Mammograms with masses corresponding to biopsy-proven cancer were processed using algorithms based on the wavelet transform. Five radiologists assessed the visibility of malignant masses in ten processed mammograms as compared with the original film images. Mammograms processed using these algorithms demonstrated some improvement in feature visualization. Wavelet-based methods of image enhancement could prove to be useful in mammography and merit further study. Correspondence to: W. Huda