PubMed · 8938490
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
R Carter. 1996. Tour de force.. https://pubmed.ncbi.nlm.nih.gov/8938490/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
Membrane overcultures of Rhizopus oligosporus were shifted from 37 to 50 degrees C for 10 h and then returned to 37 degrees C, mimicking the temporal temperature profiles which typically occur in SSF due to heat transfer limitations. Analysis with a modified two-phase growth model suggests that the temperature upshift causes a 48% decrease in the number of actively extending hyphal tips, and that the first order death rate constant of tips increases from 0. 059 to 0.073 h(-1). The fungus did not immediately recover when the temperature was returned to 37 degrees C. The model assumed that the specific growth rate constant microgram(g) was not affected by the increase of temperature, although contradictory data was obtained from radial growth rate experiments.
A common event in the development of human neoplasia is the loss of growth regulatory tumor suppressor functions. Methylation of 5' CpG islands of tumor suppressor genes and elevated levels of the DNA-(cytosine-5)-methyltransferase enzyme (DNA MeTase) are also prevalent features of human neoplasia. However, direct evidence that elevated DNA MeTase levels alter gene expression and influence oncogenesis has been difficult to obtain, in part due to the lack of specific DNA MeTase inhibitors. Here we show that specific reduction of cellular DNA MeTase levels in human cancer cells with potent antisense inhibitors: 1) causes demethylation of the p16(ink4A) gene promoter; 2) causes re-expression of the p16(ink4A) protein; 3) leads to accumulation of the hypophosphorylated form of the retinoblastoma protein (pRb); and 4) inhibits cell proliferation. Stepwise reduction of cellular DNA MeTase protein levels also induced a corresponding rapid increase in the cell cycle regulator p21(WAF/Cip1) protein demonstrating a regulatory link between DNA MeTase and the growth regulator p21(WAF/Cip1) that is independent of methylation of DNA. These results suggest that the elevated levels of DNA MeTase seen in cancer cells can inhibit tumor suppressors by distinct mechanisms involving either transcriptional inactivation through DNA methylation or by a methylation independent regulation.
Eosinophils have been associated with fibrosis. To investigate their direct role in fibrosis, human peripheral blood eosinophil sonicate was added to human lung or dermal fibroblasts, and proliferation ([(3)H]thymidine) and collagen synthesis ([(3)H]proline) were evaluated. Proliferation was enhanced significantly in the monolayers in a dose-dependent manner. The activity of the eosinophil fibrogenic factor(s) remained unaltered when heated (56 degrees C, 30 min). Supernatants of cultured eosinophils (20 min or 18 hr) also enhanced lung fibroblast proliferation, indicating that the preformed mitogenic factor(s) can be released both promptly and with a long kinetic. Eosinophils significantly decreased collagen production in lung fibroblasts while increasing it in dermal fibroblasts. However, eosinophils containing matrix metalloproteinase 9 (zymography) in latent form and tissue inhibitors of metalloproteinases 1 and 2 (reverse zymography) did not influence either fibroblast matrix metalloproteinases or tissue inhibitors of metalloproteinases. Eosinophil sonicate added to skin and lung fibroblasts in tridimensional collagen lattices significantly enhanced lattice contraction. Transforming growth factor beta (TGF-beta) is a major fibrogenic cytokine produced by eosinophils. Therefore, to assess its role, eosinophil sonicate was preincubated with anti-TGF-beta neutralizing antibodies. This treatment partially inhibited proliferation of lung and collagen synthesis of dermal fibroblasts and suppressed the stimulation of lattice contraction, indicating the fibrogenic role of eosinophil-associated TGF-beta. In conclusion, we have shown that eosinophils act as direct modulatory cells in fibroblast proliferation, collagen synthesis, and lattice contraction, in part, through TGF-beta. These data corroborate the importance of eosinophils in skin and lung fibrosis.