In severe or chronic asthma, there is an increase in airway smooth muscle cell (ASMC) mass as well as an increase in connective tissue proteins in the smooth muscle layer of airways. Transforming growth factor-beta (TGF-beta) exists in three isoforms in mammals and is a potent regulator of connective tissue protein synthesis. Using immunohistochemistry, we had previously demonstrated that ASMCs contain large quantities of TGF-beta1-3. In this study, we demonstrate that bovine ASMC-derived TGF-beta associates with the TGF-beta latency binding protein-1 (LTBP-1) expressed by the same cells. The TGF-beta associated with LTBP-1 localizes TGF-beta extracellularly. Furthermore, plasmin, a serine protease, regulates the secretion of a biologically active form of TGF-beta by ASMCs as well as the release of extracellular TGF-beta. The biologically active TGF-beta released by plasmin induces ASMCs to synthesize collagen I in an autocrine manner. The autocrine induction of collagen expression by ASMCs may contribute to the irreversible fibrosis and remodeling seen in the airways of some asthmatics.

The role of diet and fat consumption in the pathogenesis of breast cancer is an important subject. We report on a method for non-invasive determination of lipid composition in human breast by proton MRS at 7T. Two respiratory-triggered TE-averaged STEAMs were performed on the adipose tissue of ten healthy volunteers where the second acquisition had all gradients inverted. This acquisition protocol allows for suppression of modulation side bands that complicate spectral analysis at the short TEavg = 24.5 ms used. The entire acquisition takes approximately 10 minutes. Ten lipid peaks were typically resolved. T1 and T2 were also measured and used to correct the peak intensities. The average lipid composition calculated was saturated 28.7 ± 8.4%, monounsaturated 48.5 ± 7.9 %, and polyunsaturated 22.7 ± 3.1%, in close agreement with reported values from subcutaneous adipose measurements. Intra-subject variability was 2.0, 1.6, and 3.6% for the saturated, monounsaturated, and polyunsaturated fractions, respectively. In conclusion, we have shown that a chemical analysis of lipids in breast tissue can be determined quite simply, quickly, and non-invasively by proton MRS at 7T.