Heme oxygenase-1 gene induction as an intrinsic regulation against delayed cerebral vasospasm in rats.
(9/1051)
Delayed cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) causes cerebral ischemia and infarction. To date, the pathogenesis and gene expression associated with vasospasm remain poorly understood. The present study used fluorescent differential display to identify differentially expressed genes in a rat model of SAH. By using quantitative RT-PCR, we found that heme oxygenase-1 (HO-1) mRNA was prominently induced in the basilar artery and modestly in brain tissue in a rat vasospasm model. A significant correlation was observed between the degree of vasospasm and HO-1 mRNA levels in the basilar arteries exhibiting vasospasm. Intracisternal injection of antisense HO-1 oligodeoxynucleotide (ODN) significantly delayed the clearance of oxyhemoglobin and deoxyhemoglobin from the subarachnoid space and aggravated angiographic vasospasm. Antisense HO-1 ODN inhibited HO-1 induction in the basilar arteries but not in the whole brain tissue. This phenomenon was not observed in the nontreated, sense HO-1 ODN-treated, or scrambled ODN-treated arteries. We report the protective effects of HO-1 gene induction in cerebral vasospasm after SAH, a finding that should provide a novel therapeutic approach for cerebral vasospasm. (+info)
Pro-B-cell-specific transcription and proapoptotic function of protein kinase Ceta.
(10/1051)
Using a subtractive cloning scheme on cDNA prepared from primary pro-B and pre-B cells, we identified several genes whose products regulate apoptosis. We further characterized one of these genes, encoding protein kinase Ceta (PKCeta). PKCeta transcripts were readily detected in pro-B cells but were absent in pre-B cells. Although both a full-length and a truncated form of PKCeta were detectable in bone marrow pro-B cells, transition to the pre-B-cell stage was associated with increased relative levels of truncated PKCeta. We found that PKCeta is proteolyzed in apoptotic lymphocytes, generating a kinase-active fragment identical to the truncated form which is capable of inducing apoptosis when expressed in a pro-B cell line. Caspase-3 can generate an identical PKCeta cleavage product in vitro, and caspase inhibitors prevent the generation of this product during apoptosis in transfected cell lines. Inducible overexpression of either the full-length or truncated form of PKCeta results in cell cycle arrest at the G(1)/S transition. These results suggest that the expression and proteolytic activation of PKCeta play an important role in the regulation of cell division and cell death during early B-cell development. (+info)
Expression scanning of an array of growth control genes in human tumor cell lines.
(11/1051)
Analysis of gene expression on a medium- or large-scale is an increasingly recognized method for functional and clinical investigations based on the now extensive catalog of known or partially sequenced genes. The accessibility of this approach can be enhanced by using readily available technology (macroarrays on Nylon, radioactive detection) and the IMAGE resource to assemble sets of targets. We have set up such a medium-scale, flexible system and validated it by the study of quantitative expression levels for 120 genes in six cell lines, including three mammary carcinoma cell lines. A number of important parameters are identified as necessary for the assembly of a valid set and the obtention of good-quality quantitative data. The extensive data assembled in this survey identified potential targets of carcinogenesis, for example the CRABP2 and GATA3 transcription factor genes. We also demonstrate the feasibility of this procedure for relatively small tumor samples, without recourse to probe amplification methods. (+info)
Effects of scatter substraction on detection and quantitation in hepatic SPECT.
(12/1051)
The purpose of this investigation was to examine the effects of subtractive scatter compensation methods on lesion detection and quantitation. METHODS: Receiver operating characteristic (ROC) methodology was used to measure human observer detection accuracy for tumors in the liver using synthetic images. Furthermore, ROC results were compared with mathematical models for detection and activity quantitation to examine (a) the potential for predicting human performance and (b) the relationship between the detection and quantitation tasks. Images with both low and high amounts of scatter were compared with the ideal case of images of primary photons only (i.e., perfect scatter rejection) and with images corrected by subtracting a scatter image estimated by the dual photopeak window method. RESULTS: With low contrast tumors in a low count background, the results showed that scatter subtraction improved quantitation but did not produce statistically significant increases in detection accuracy. However, primary images did produce some statistically significant improvements in detection accuracy when compared with uncorrected images, particularly for high levels of scatter. CONCLUSION: Although scatter subtraction methods may provide improved activity quantitation, they may not significantly improve detection for liver SPECT. The results imply that significant improvement in detection accuracy for the conditions tested may depend on the development of gamma cameras with better scatter rejection. (+info)
Racial differences in the significance of coronary calcium in asymptomatic black and white subjects with coronary risk factors.
(13/1051)
OBJECTIVES: To compare the significance of a specific feature of coronary atherosclerosis--coronary calcium--in asymptomatic black and white subjects with coronary risk factors. BACKGROUND: The natural history and clinical evolution of coronary atherosclerosis differs between blacks and whites. Differences in the underlying pathobiology of atherosclerosis may be one determinant of the ethnic variability in the clinical manifestation of coronary atherosclerosis. METHODS: In 1,375 high-risk but asymptomatic subjects (93 blacks [6.8%] and 1,282 whites [93.2%]) with at least one risk factor but no prior evidence of coronary disease, we assessed coronary risk factors, calculated Framingham risk of a coronary event and evaluated coronary calcium with digital subtraction fluoroscopy. We then followed these subjects clinically for 70 +/- 13 months, noting the occurrence of the following coronary events: death due to coronary heart disease (CHD); myocardial infarction (MI); angina pectoris; and performance of coronary bypass or angioplasty. RESULTS: Risk factor profiles were similar in black and white subjects (6-year Framingham risk 15 +/- 7% in blacks, 14 +/- 8% in whites [NS]). Coronary calcium was present in 59.9% of white subjects but only 35.5% of black subjects (p = 0.0001). Nevertheless, after 70 months of follow-up, more blacks than whites (22 blacks [23.7%] vs. 190 whites [14.8%]; p = 0.04) suffered one of the following end points: CHD death, MI, angina or revascularization. The age, gender and coronary risk-adjusted odds ratio of black race for at least one event was 2.16 (95% CI 1.34 to 3.48). CONCLUSIONS: Despite having a lowered prevalence of coronary calcium than high risk whites, high risk blacks suffer more CHD events. Coronary calcium therefore does not carry the same pathobiologic significance in blacks that it does in whites, consistent with the concept that there are specific racial differences in the natural history of CHD and its evolution into clinically manifest events. (+info)
Profound misregulation of muscle-specific gene expression in facioscapulohumeral muscular dystrophy.
(14/1051)
Facioscapulohumeral muscular dystrophy (FSHD) is a neuromuscular disorder characterized by an insidious onset and progressive course. The disease has a frequency of about 1 in 20,000 and is transmitted in an autosomal dominant fashion with almost complete penetrance. Deletion of an integral number of tandemly arrayed 3.3-kb repeat units (D4Z4) on chromosome 4q35 is associated with FSHD but otherwise the molecular basis of the disease and its pathophysiology remain obscure. Comparison of mRNA populations between appropriate cell types can facilitate identification of genes relevant to a particular biological or pathological process. In this report, we have compared mRNA populations of FSHD and normal muscle. Unexpectedly, the dystrophic muscle displayed profound alterations in gene expression characterized by severe underexpression or overexpression of specific mRNAs. Intriguingly, many of the deregulated mRNAs are muscle specific. Our results suggest that a global misregulation of gene expression is the underlying basis for FSHD, distinguishing it from other forms of muscular dystrophy. The experimental approach used here is applicable to any genetic disorder whose pathogenic mechanism is incompletely understood. (+info)
B7h, a novel costimulatory homolog of B7.1 and B7.2, is induced by TNFalpha.
(15/1051)
In a screen to identify genes induced by NF-kappaB/Rel transcription factors, we cloned a novel gene, b7h, that is a close homolog of B7 costimulatory ligands expressed on antigen-presenting cells. B7h can costimulate proliferation of purified T cells through a receptor on T cells distinct from CD28 or CTLA-4. Surprisingly, although B7h is expressed in unstimulated B cells, its expression is induced in both 3T3 cells and embryonic fibroblasts treated with TNFalpha, and it is upregulated in nonlymphoid tissues of mice treated with LPS, a potent activator of TNFalpha. These data define a novel costimulatory ligand for T cells and suggest that induction of B7h by TNFalpha may function as a mechanism to directly augment recognition of self during inflammation. (+info)
Comparison of the quality of temporal subtraction images obtained with manual and automated methods of digital chest radiography.
(16/1051)
The authors have been developing a fully automated temporal subtraction scheme to assist radiologists in the detection of interval changes in digital chest radiographs. The temporal subtraction image is obtained by subtraction of a previous image from a current image. The authors' automated method includes not only image shift and rotation techniques but also a nonlinear geometric warping technique for reduction of misregistration artifacts in the subtraction image. However, a manual subtraction method that can be carried out only with image shift and rotation has been employed as a common clinical technique in angiography, and it might be clinically acceptable for detection of interval changes on chest radiographs as well. Therefore, the authors applied both the manual and automated temporal subtraction techniques to 181 digital chest radiographs, and compared the quality of the subtraction images obtained with the two methods. The numbers of clinically acceptable subtraction images were 147 (81.2%) and 176 (97.2%) for the manual and automated subtraction methods, respectively. The image quality of 148 (81.8%) subtraction images was improved by use of the automated method in comparison with the subtraction images obtained with the manual method. These results indicate that the automated method with the nonlinear warping technique can significantly reduce misregistration artifacts in comparison with the manual method. Therefore, the authors believe that the automated subtraction method is more useful for the detection of interval changes in digital chest radiographs. (+info)