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Exposure to ambient particulate matter (PM) significantly increases cardiovascular morbidity and mortality in the general population. We hypothesized that some components of PM can affect the gene expression patterns in the hearts of rats exposed for 3 months to filtered air (FA), coarse (CP; 2.5 < d < 10 μm), fine (FP; d ≤ 2.5 μm) or ultrafine (UFP; d ≤ 0.18 μm) components of PM. The median diameters of CP, FP, and UFP were 3 μm, 0.7 μm and 0.07 μm, respectively. Exposures ( n = 8 per group) were performed using a particle concentrator system in Riverside, California, an area with high ambient levels of photochemically derived gaseous and particulate pollutants. At the end of the exposure, hearts were subjected to gene expression profiling by using Illumina RatRef-12 bead chips and levels of malonaldehyde (MDA), a biomarker of oxidative stress, were measured. Applying fold ratio >1.5 (for both up- and down-regulated genes), we found three genes in the CP and nine genes in the UFP groups with significantly changed expression, compared with FA. No significant changes in gene expression patterns were observed in the FP group. In the UFP group thioredoxin interacting protein (Txnip), a negative regulator of an antioxidant enzyme thioredoxin, and cytochrome P450 (Cyp2e1), an enzyme involved in the metabolism of foreign substances demonstrated significant up-regulation (fold ratios 1.79 and 1.57, respectively, with false discovery rate, FDR < 0.05). In the CP group there was also a trend towards increased Txnip expression (fold ratio 1.43, FDR > 0.05) and significant increase in the Cyp2e1 expression (fold ratio 1.79, FDR < 0.05). Changes in the Txnip and Cyp2e1 expression showed statistically significant positive correlation to each other ( p < 0.0009) and were confirmed by real-time PCR. In addition Txnip and Cyp2e1 expression demonstrated statistically significant moderate correlation with the levels of MDA in the heart. Up-regulation of both Cyp2e1 and Txnip are observed in hearts of patients with certain cardiac diseases. Therefore, chronic exposure to CP and UFP directly affects expression of disease-relevant genes in the myocardium. [ABSTRACT FROM AUTHOR]

Amelogenesis imperfecta (AI) is a collective term used to describe phenotypically diverse forms of defective tooth enamel development. AI has been reported to exhibit a variety of inheritance patterns, and several loci have been identified that are associated with AI. We have performed a genome-wide scan in a large Brazilian family segregating an autosomal dominant form of AI and mapped a novel locus to 8q24.3. A maximum multipoint LOD score of 7.5 was obtained at marker D8S2334 (146,101,309 bp). The disease locus lies in a 1.9 cM (2.1 Mb) region according to the Rutgers Combined Linkage-Physical map, between a VNTR marker (at 143,988,705 bp) and the telomere (146,274,826 bp). Ten candidate genes were identified based on gene ontology and microarray-facilitated gene selection using the expression of murine orthologues in dental tissue, and examined for the presence of a mutation. However, no causative mutation was identified. [ABSTRACT FROM AUTHOR]

Identification of distinct molecular subtypes is a critical challenge for cancer biology. In this study, we used Affymetrix high-density oligonucleotide arrays to identify the global gene expression signatures associated with gliomas of different types and grades. Here, we show that the global transcriptional profiles of gliomas of different types and grades are distinct from each other and from the normal brain. To determine whether our data could be used to uncover molecular subtypes without prior knowledge of pathologic type and grade, we performed K-means clustering analysis and found evidence for three clusters with the aid of multidimensional scaling plots. These clusters corresponded to glioblastomas, lower grade astrocytomas and oligodendrogliomas (P<0.00001). A predictor constructed from the 170 genes that are most differentially expressed between the subsets correctly identified the type and grade of all samples, indicating that a relatively small number of genes can be used to distinguish between these molecular subtypes. These results further define molecular subsets of gliomas which may potentially be used for patient stratification, and suggest potential targets for treatment.Oncogene (2003) 22, 4918-4923. doi:10.1038/sj.onc.1206753 [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR) overexpression occurs in nearly 50% of cases of glioblastoma (GBM), but its clinical and biological implications are not well understood. We have used Affymetrix high-density oligonucleotide arrays to demonstrate that EGFR-overexpressing GBMs (EGFR+) have a distinct global gene transcriptional profile. We show that the expression of 90 genes can distinguish EGFR+ from EGFR nonexpressing (EGFR-) GBMs, including a number of genes known to act as growth/survival factors for GBMs. We have also uncovered two additional novel molecular subtypes of GBMs, one of which is characterized by coordinate upregulation of contiguous genes on chromosome 12q13-15 and expression of both astrocytic and oligodendroglial genes. These results define distinct molecular subtypes of GBMs that may be important in disease stratification, and in the discovery and assessment of GBM treatment strategies.Oncogene (2003) 22, 2361-2373. doi:10.1038/sj.onc.1206344 [ABSTRACT FROM AUTHOR]