ABSTRACT
Basic fibroblast growth factor (bFGF) is a major mitogen and chemoattractant for many cell types. The synergistic role of fetal bovine serum (FBS) and heparin on the modulation of tissue-cultured bovine corneal endothelial cells by bFGF was studied. Cell modulation was assessed by DNA synthesis ([3H]thymidine incorporation), mitochondrial activity (MTT assay), mitochondrial volume (transmission electron microscope study), and cell shape in mitotically competent cells and cells mitotically inhibited by 5-fluorouracil, mitomycin C, and irradiation. The dose-dependent stimulation of bFGF was found to be different for DNA synthesis and mitochondrial activity, the maximal effective dose being 1 and 10 ng/ml, respectively. Supplementation of bFGF with FBS enhanced both DNA synthesis and mitochondrial activity and caused a shift in the dose response to lower bFGF concentrations for the DAN synthesis, but not for the mitochondrial activity. Supplementation of bFGF with heparin resulted in an additional response for the mitochondrial activity, but not for the DNA synthesis. In addition, bFGF increased mitochondrial volume and induced elongation of the cells. These processes were further enhanced by the addition of heparin to bFGF. These results suggest that serum and heparin have a differential effect on mitogenic and non-mitogenic cells processes modulated by bFGF.
Subject(s)
Blood , DNA/biosynthesis , Endothelium, Corneal/drug effects , Fibroblast Growth Factor 2/pharmacology , Heparin/pharmacology , Mitochondria/drug effects , Animals , Cattle , Cell Size/drug effects , Cells, Cultured , Dose-Response Relationship, Drug , Drug Synergism , Endothelium, Corneal/cytology , Endothelium, Corneal/ultrastructure , Microscopy, Electron , Mitochondria/physiologyABSTRACT
We evaluated the histopathologic findings in seven patients who underwent surgical revision of the filtration site after trabeculectomy with mitomycin C because of persistent hypotonous maculopathy. Light microscopic examination of subconjunctival tissue and sclera demonstrated hypocellularity of fibroblasts and disruption of the normal architecture. Tissue fragments at the margin of the bleb wall demonstrated scarring and contained multiple fibroblasts. Additionally, we investigated the histopathologic changes in an eye obtained from a patient who died one week after a trabeculectomy with mitomycin C. Transmission electron microscopy showed myelin figures, increased melanolipofuscin granules, vacuolated cytoplasm, and disrupted mitochondria of the ciliary body epithelium underlying the site of mitomycin C application. On the basis of these findings, both overfiltration because of tissue disorganization of the filtering bleb and aqueous hyposecretion because of ciliary body toxicity might be involved in the causes of persistent hypotony after mitomycin C trabeculectomy.
Subject(s)
Glaucoma/pathology , Mitomycin/pharmacology , Ocular Hypotension/pathology , Trabeculectomy , Adult , Aged , Ciliary Body/drug effects , Ciliary Body/ultrastructure , Combined Modality Therapy , Conjunctiva/drug effects , Conjunctiva/ultrastructure , Female , Fluorouracil/administration & dosage , Glaucoma/therapy , Humans , Male , Middle Aged , Ocular Hypotension/etiology , Ocular Hypotension/therapy , Reoperation , Sclera/drug effects , Sclera/ultrastructure , Surgical Flaps/pathology , Suture Techniques/adverse effectsABSTRACT
PURPOSE: Platelet-derived growth factor (PDGF), a major mitogen and chemoattractant, is a dimeric molecule of disulfide-bonded A and/or B polypeptide chains (PDGF-AA/AB/BB). Two PDGF receptors (PDGFR) exist, alpha and beta, which dimerize after ligand exposure. The alpha-receptor binds both A- and B-chains, whereas the beta-receptor preferentially binds the B-chain. Whether PDGFR are present on, and whether PDGF is mitogenic for, corneal cells was investigated. METHODS: For receptor determination, a two-step immunoperoxidase technique with monoclonal antibodies against both alpha- and beta-receptors was applied on frozen sections of human and bovine corneas. To test the mitogenic activity of PDGF-BB, two proliferation assays, the DNA synthesis assay (3H-thymidine incorporation) and the colorimetric MTT assay, were used for cultured bovine corneal endothelial cells (BCEC) and human corneal fibroblast (HCF). RESULTS: Both receptors were present on epithelial cells, stromal fibroblasts, and endothelial cells, the beta-receptor being most abundant. In BCEC, minimal and maximal effects on DNA synthesis occurred at 10 ng/ml and 50-100 ng/ml PDGF, respectively. For HCF, the minimal and maximal effective doses were 1 ng/ml and 25-100 ng/ml of PDGF, respectively. The MTT assay, carried out in BCEC only, showed a minimal and maximal cell activity at 1 ng/ml and 10-100 ng/ml of PDGF, respectively. CONCLUSIONS: The presence of PDGFR in human corneal epithelium, fibroblasts, and endothelium and the mitogenic effects of PDGF on corneal cells indicate that PDGF may play a role in corneal wound healing.
Subject(s)
Cornea/chemistry , Platelet-Derived Growth Factor/pharmacology , Receptors, Platelet-Derived Growth Factor/analysis , Aged , Animals , Cattle , Cell Division , Cells, Cultured , DNA/biosynthesis , Endothelium, Corneal/chemistry , Fibroblasts/chemistry , Humans , Immunoenzyme Techniques , Middle AgedABSTRACT
A possibly new type of T cell pseudolymphoma is described in three cases. It presented as a small, solitary lesion on the trunk of 3 to 5 months' duration. It was slightly elevated, round, and erythematous, with a diameter of 1 to 2 cm. It showed a tendency to regress spontaneously. In sharp contrast to its benign clinical appearance and biologic behavior, a distinct malignant histopathologic picture was observed, however. It was characterized by a nonepidermotropic bandlike subepidermal infiltrate dominated by large T lymphocytes with cerebriform nuclei identical in morphologic and immunologic characteristics to the abnormal cellular component of cutaneous T-cell lymphomas.
