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Biomedical subjects

D R Edwards

Publications and source records attributed to D R Edwards.

111 records · Page 7Linked to original sources

Differential effects of transforming growth factor-beta 1 on the expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in young and old human fibroblasts.

The balance between the activities of matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs) is an important control point in tissue remodeling. Previous studies have demonstrated elevated expression of the MMPs collagenase and stromelysin-1 by aged human diploid fibroblasts compared to early-passage cultures. We show here that aging cells display an altered response to transforming growth factor-beta 1 (TGF beta 1) that selectively affects MMP mRNA expression. In both young and old cells, phorbol myristoyl-13 acetate (PMA) induced the expression of transcripts of collagenase, stromelysin-1, gelatinase-B, TIMP-1, and TIMP-3. In young cells, TGF beta 1 reciprocally modulated PMA-induced MMP and TIMP gene expression leading to reduced levels of transcripts for the MMPs and augmented accumulation of TIMP-1 and TIMP-3 mRNAs. However, repressing effects of TGF beta 1 on collagenase, stromelysin-1, and gelatinase-B RNA expression were not apparent in old cells, though induction of the TIMP genes was unimpaired. By electrophoretic mobility shift analysis the nuclear transcription factors AP1 and serum response factor (SRF) showed reduced levels of DNA binding activities in old fibroblasts compared to young cells. A probe for the TGF beta-inhibitory element (TIE) gave equivalent levels of complexes with nuclear extracts from both types of cells, though of different mobilities. We conclude that the effects of TGF beta 1 on MMP and TIMP gene expression involve different cellular intermediaries, and suggest that altered composition or modification of TIE binding factors in aging cells may underlie the failure of TGF beta 1-mediated transcription repression. This mechanism may contribute to elevated constitutive expression of MMPs in old cells and to the connective tissue deterioration that accompanies the aging process.

Cells, Cultured↗

Effects of alum and aluminum chloride on phosphorus runoff from swine manure.

Phosphorus (P) runoff from fields fertilized with swine (Sus scrofa domesticus) manure may contribute to eutrophication. The objective of this study was to evaluate the effect of aluminum sulfate (alum) and aluminum chloride applications to swine manure on P runoff from small plots cropped to tall fescue (Festuca arundinacea Shreb.). There were six treatments in this study: (i) unfertilized control plots, (ii) untreated manure, (iii) manure with alum at 215 mg Al L(-1), (iv) manure with aluminum chloride at 215 mg Al L(-1), (v) manure with alum at 430 mg Al L(-1), and (vi) manure with aluminum chloride at 430 mg Al L(-1). Manure application rates were equivalent to approximately 125 kg N ha(-1). Alum and aluminum chloride additions lowered soluble reactive phosphorus (SRP) levels from about 130 mg P L(-1) to approximately 30 mg P L(-1) at low rates. At high rates, SRP levels in swine manure were around 1 mg P L(-1). Soluble reactive P concentrations in runoff were 5.50, 3.66, 3.00, 0.87, 0.87, and 0.55 mg P L(-1), for normal manure, low alum, low aluminum chloride, high alum, high aluminum chloride, and unfertilized control plots, respectively. Hence, high alum and aluminum chloride reduced SRP concentrations in runoff by 84% and were not statistically different from SRP concentrations in runoff from unfertilized control plots. These data indicate that treating swine manure with alum or aluminum chloride could result in significant reductions in nonpoint-source P runoff.

Alum Compounds↗

Lymph node metastases from glioblastoma multiforme.

Extraneural metastases from glioblastoma multiforme are rare. Spread to the extracranial head and neck may be evident on routine follow-up images of the original lesion. We present two cases, one with documented metastatic adenopathy in the head and neck from glioblastoma and the other with probable metastatic disease in a lymph node in which biopsy was not performed, and discuss probable mechanisms of extraneural extension of this tumor.

Adult↗