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Biomedical subjects

P R Nelson

Publications and source records attributed to P R Nelson.

24 records · Page 2Linked to original sources
PubMed1996

Differential effects of platelet-derived growth factor isotypes on human smooth muscle cell proliferation and migration are mediated by distinct signaling pathways.

BACKGROUND: Platelet-derived growth factor (PDGF) is a potent mitogen and chemoattractant for vascular smooth muscle cells (SMCs). Three isotypes of PDGF (BB, AB, and AA) have been identified; each of these isotypes may have differing effects on the behaviour of vascular SMCs. In this study we evaluated the influence of PDGF isotypes on proliferation and migration of human venous SMCs and explored the signaling pathways through which these effects are mediated. METHODS: Proliferation was measured by a 72-hour assay of cell number, and migration was evaluated by a 4-hour microchemotaxis assay. The effects of PDGF isotypes on the activities of the signaling proteins mitogen-activated protein kinase (MAP-K), p 125 focal adhesion kinase (p125FAK), and tensin were measured by immunoprecipitation of these proteins and subsequent phosphorylation on myelin basic protein (in MAP-K) and Western blotting with antiphosphotyrosine (in tensin and p125FAK). RESULTS: All three isotypes stimulated SMC proliferation (PDGF-BB > AB > AA). PDGF-BB and -AB, but not -AA, stimulated chemotaxis. All three isotypes activated MAP-K with an intensity that corresponded to their proliferative effects. PDGF-BB and -AB tyrosine phosphorylated tensin and p125FAK, whereas PDGF-AA had no effect on either of these proteins. CONCLUSIONS: For human vascular SMCs the physiologic effects and the signaling pathways that mediate these effects are specific for each of the three PDGF isotypes. These data also suggest an association between MAP-K and SMC proliferation and between the proteins, p125FAK and tensin, and migration.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1996

Extracellular matrix proteins are potent agonists of human smooth muscle cell migration.

PURPOSE: Extracellular matrix proteins can stimulate smooth muscle cell (SMC) migration by three distinct mechanisms: chemokinesis (nondirected migration in the presence of soluble protein), chemotaxis (directed migration toward soluble protein), and haptotaxis (directed migration toward insoluble, substrate-bound protein). This study investigates the effects of four prevalent extracellular matrix proteins (collagen types I and IV, fibronectin, and laminin), and platelet-derived growth factor (PDGF) on haptotaxis, chemotaxis, and chemokinesis of human SMCs. The role of large guanosine triphosphate-binding proteins (G-proteins) in the signaling mediating these effects is also evaluated. METHODS: Human saphenous vein SMCs were used in all migration studies. Chemokinesis, chemotaxis, and haptotaxis to each of the matrix proteins were measured and compared with PDGF through the use of a 48-well microchemotaxis chamber. The role of G-proteins in matrix-induced SMC migration was studied with the modulators of G-protein function, cholera and pertussis toxins. RESULTS: For all matrix proteins the relative strength of the various stimuli for migration was haptotaxis > chemotaxis > chemokinesis (p < 0.05). For all three stimuli collagen I and IV produced the most significant migration followed by fibronectin > PDGF-AB > laminin (p < 0.05). Pertussis toxin completely inhibited chemotaxis and partially inhibited haptotaxis by laminin but did not affect migration by other matrix proteins, whereas cholera toxin abolished migration in response to all four matrix proteins. CONCLUSION: Matrix proteins, with the exception of laminin, provide a more significant stimulus for SMC locomotion than does the prototypical agonist, PDGF-AB. Of the three mechanisms by which migration can be stimulated, haptotaxis elicits the most profound effect. The importance of G-proteins as second messengers for migration varies with each matrix protein and with the mechanism of stimulation.

Cell Movement↗
PubMed1994

Cutaneous zygomycosis caused by Saksenaea vasiformis in a diabetic patient.

A 49-year-old woman with diabetes mellitus rapidly developed necrotizing cellulitis with fat necrosis and vasculitis after minor trauma to the right arm. Zygomycosis was diagnosed histologically. The lesion responded to aggressive debridement, amphotericin B, and normalization of blood glucose. Cultures yielded structures characteristic of Saksenaea vasiformis only after transfer to saline agar.

Dermatomycoses↗
PubMed1992

Healing of full-thickness cartilage compared with full-thickness cartilage and subchondral bone defects in the equine third carpal bone.

The effect of lesion depth on the quality of third carpal bone cartilage repair was examined. A 1-cm diameter articular defect penetrating the calcified cartilage in one limb and the subchondral bone plate in the opposite limb was created in the radial facet of the third carpal bones. Clinical and xeroradiographic examinations were performed every 4 weeks until 4 months (3 horses) and 6 months (3 horses) after surgery. The synovial membrane, non-opposing articular surfaces and articular defects were examined grossly, histologically and histochemically. Grossly, deeper defects contained thicker, whiter tissue, but both joints contained generalised degenerative changes. Defects extending through calcified cartilage were filled deeply by fibrocartilage and superficially by fibrous connective tissue. Defects extending through subchondral bone were consistently filled with hyaline-like cartilage in the depths of the lesion, fibrocartilage in the intermediate layer and fibrous connective tissue superficially. The results indicate that subchondral bone is the source of hyaline-like cartilage repair tissue and suggest that quality of healing of cartilage defects may be improved by penetrating the subchondral bone plate. It also appears that the synovitis associated with the procedure must be controlled before the procedure can be advocated for treatment of clinical cases.

Animals↗
PubMed1992

Comparison of two grafting methods in 4.0-mm drill defects in the third metacarpal bone of horses.

In 6 horses, bilateral metacarpal vertical series of three 4.0-mm unicortical drill holes were made. At random, one of each series of 3 holes was filled using a sternal 4.0-mm cancellous bone cylinder or a slurry of cancellous bone injected into the hole or left as an empty control. All horses had lateral metacarpal xeroradiographs at monthly intervals. Three horses (6 metacarpi) were examined post mortem after 4 months and 3 others after 6 months. Immediate through 4-month post-operative xeroradiographs demonstrated increased density in the holes with cancellous cylinders and no difference could be seen between the untreated controls and holes injected with slurry. From 5 months, no radiographic difference could be seen between the treatment groups. No consistent histological difference between treatment groups could be detected. In conclusion, no justification for clinical grafting of 4.0-mm unicortical dorsal metacarpal drill holes could be found.

Animals↗