Global correlation of genome and transcriptome changes in classical Hodgkin lymphoma

To identify genes involved in the pathogenesis of classical Hodgkin lymphoma (cHL), we performed serial analysis of gene expression (SAGE) and array-based comparative genomic hybridization (aCGH). Comparison of SAGE libraries of cHL cell lines L428 and L1236 with that of germinal centre B cells revealed consistent overexpression of only 14 genes. In contrast, 141 genes were downregulated in both cHL cell lines, including many B cell and HLA genes. aCGH revealed gain of 2p, 7p, 9p, 11q and Xq and loss of 4q and 11q. Eighteen percent of the differentially expressed genes mapped to regions with loss or gain and a good correlation was observed between underexpression and loss or overexpression and gain of DNA. Remarkably, gain of 2p and 9p did not correlate with increased expression of the proposed target genes c-REL and JAK2. Downregulation of many genes within the HLA region also did not correlate with loss of DNA. FSCN1 and IRAK1 mapping at genomic loci (7p and Xq) that frequently showed gain were overexpressed in cHL cell lines and might be involved in the pathogenesis of cHL.     

Johanson–Blizzard syndrome—A case study of oral and systemic manifestations

Johanson–Blizzard syndrome is a hereditary disorder extremely rare. The characteristic features include aplastic alae nasi, midline ectodermal scalp defects, deafness, dental abnormalities and malabsorption related to pancreatic exocrine deficiency. This paper presents a case of an 18-year-old patient with Johanson–Blizzard syndrome and emphasizes the importance of knowledge of the potential anaesthetic concerns of this syndrome for providing appropriate treatment for these patients.     

Bone marrow-derived mononuclear cells vs. mesenchymal stromal cells in experimental allergic asthma

We compared the effects of bone marrow-derived mononuclear cells (BMMCs) and mesenchymal stromal cells (MSCs) on airway inflammation and remodeling and lung mechanics in experimental allergic asthma. C57BL/6 mice were sensitized and challenged with ovalbumin (OVA group). A control group received saline using the same protocol. Twenty-four hours after the last challenge, groups were further randomized into subgroups to receive saline, BMMCs (2 × 10⁶) or MSCs (1 × 10⁵) intratracheally. BMMC and MSC administration decreased cell infiltration, bronchoconstriction index, alveolar collapse, collagen fiber content in the alveolar septa, and interleukin (IL)-4, IL-13, transforming growth factor (TGF)-β and vascular endothelial growth factor (VEGF) levels compared to OVA-SAL. Lung function, alveolar collapse, collagen fiber deposition in alveolar septa, and levels of TGF-β and VEGF improved more after BMMC than MSC therapy. In conclusion, intratracheal BMMC and MSC administration effectively modulated inflammation and fibrogenesis in an experimental model of asthma, but BMMCs was associated with greater benefit in terms of reducing levels of fibrogenesis-related growth factors.     

Cellular sources of transforming growth factor-alpha in human oral cancer

Aberrant expression of TGF-alpha is associated with human malignant oral epithelium. Experiments were initiated to determine the cellular sources of transforming growth factor-alpha (TGF-alpha) in human oral cancer. Ten freshly resected human oral cancers and four specimens of normal human oral epithelium were studied by in situ hybridization and immunohistochemistry. Tissues were probed with 35S-labeled sense and antisense riboprobes to (i) human TGF-alpha (hTGF-alpha), (ii) human epidermal growth factor receptor (EGFR) to determine the distribution of TGF-alpha responsive cells, and (iii) histone H3 to examine TGF-alpha and/or EGFR's possible contribution to altered proliferation in transformed epithelium. Results of our experiments showed that TGF-alpha mRNA could be detected in normal and transformed human oral epithelium. More surprising, we have identified the major source of TGF-alpha mRNA to be the infiltrating eosinophils. A monoclonal antibody to the mature human TGF-alpha peptide stained similar areas in normal and malignant specimens. Eosinophils associated with tumors exhibited positive cytoplasmic immunostaining for TGF-alpha protein. Labeling of EGFR mRNA in human oral epithelium demonstrated uniform labeling of basal layers in normal, hyperplastic, and mildly dysplastic epithelium. In severely dysplastic epithelium and carcinomas (particularly moderate to poorly differentiated types), cellular levels of EGFR mRNA were significantly higher. The profile of altered cellular levels of EGFR mRNA correlated well with the profile of altered proliferation as indicated by H3 mRNA labeling. We hypothesize that the overproduction of EGFR mRNA in tumor epithelium--together with the localized delivery of high amounts of TGF-alpha by eosinophils at tumor-developing sites--is responsible for the increased proliferation of the tumor epithelium.     

Production of Transforming Growth Factor Alpha by Hamster Eosinophils

Previously it was demonstrated that malignant transformation of the Syrian hamster cheek pouch mucosa is associated with the expression of TGF-alpha. Therefore in situ hybridization and immunohistochemistry was used to investigate the cellular sources of TGF-alpha production in this model system. Surprisingly one cell type in the inflammatory infiltrate present in the connective tissue adjacent to the transformed epithelium represented a major source of TGF-alpha mRNA. Detailed analysis of these cells revealed that they were eosinophils. In addition to TGF-alpha mRNA, about 40% of the eosinophils associated with the oral tumors exhibited TGF-alpha product reactive with a monoclonal antibody against the C terminus of the mature TGF-alpha peptide. Normal hamster bone marrow eosinophils also exhibited TGF-alpha mRNA and product by in situ hybridization and immunohistochemistry. These results suggest that the eosinophil represents a biologically significant source of TGF-alpha.     

Effect of “This Side Up” T-shirts on Infant Sleep Position

Objectives: To assess the impact of “This Side Up” T-shirts on parental practices in Nebraska. Methods: A random sample of 3,210 Nebraska women who gave birth in 2004, stratified by race/ethnicity, was mailed a brief questionnaire on their receipt of a T-shirt and SIDS risk reduction materials at their birthing hospital, and on infant sleep position. Results: Response rates were low (25.9%), ranging from 10.6% for Native American mothers to 46.4% for White mothers. Half (52.0%) had received a T-shirt and 71.6% had received SIDS information. Two-thirds (64.0%) reported that their infants slept on their backs; African-American and Hispanic infants were significantly less likely to back sleep. In univariate logistic regression models, African-American race, Hispanic ethnicity and maternal age 30–39 were significant negative predictors of back sleeping; White race and having received a SIDS brochure were positive predictors. In the fully controlled model African American and Asian race and Hispanic ethnicity were negative predictors of back sleeping; neither receiving SIDS information nor the infant T-shirt was significant. Effects of maternal age and a SIDS informational brochure appeared in models stratified by race/ethnicity. Conclusions: In these data, receiving an infant T-shirt was not related to how mothers placed their infants to sleep. Additional research is needed on effective methods of delivering targeted counseling and promoting safe sleep practices among families, particularly among racial and ethnic subgroups.