Resonant magnetotunneling through individual self-assembled InAs quantum dots.
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Biomedical subjects
Publications and source records attributed to P Moriarty.
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PURPOSE: To characterise changes in intravitreal growth factor profiles following retinal photocoagulation in the miniature pig. METHODS: Miniature pig eyes underwent scatter photocoagulation by either diode infrared or emerald green laser. Animals were sacrificed at various times (up to 42 days) post-laser. The eyes were than removed and vitreous samples analysed for basic fibroblast growth factor, insulin-like growth factor-I and epidermal growth factor by radioimmunoassay, transforming growth factor-beta 2 by ELISA and insulin-like growth factor binding proteins using Western ligand blotting. RESULTS: Vitreous transforming growth factor-beta 2 levels were decreased at 1 h post diode laser and at 4 and 7 days post emerald laser but returned to normal by 21 and 42 days respectively. Vitreous insulin-like growth factor-I levels increased at 4 and 7 days post diode and emerald laser respectively but returned to normal by 21 days. Insulin-like growth factor Western ligand blotting demonstrated that a 34 kDa insulin-like growth factor binding protein was predominant in the pig vitreous; the levels of this binding protein followed an identical trend to those observed for insulin-like growth factor-I. No changes in vitreous levels of either basic fibroblast growth factor or epidermal growth factor were observed following laser treatment. CONCLUSIONS: Our results demonstrate a significant shift in the balance of intravitreal growth factors following retinal laser photocoagulation. Such changes may be pertinent to the regression of preretinal new vessels after laser photocoagulation.
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Vasoproliferative retinopathies result from retinal capillary non-perfusion and consequent inner retinal hypoxia. However, it is not known whether oxygen mediates vasoproliferation directly (at the nuclear level) or indirectly by regulating the production of growth factors. We have investigated the effect of oxygen on the production of basic fibroblast growth factor and transforming-growth-factor-beta by a variety of retinal cell types in culture. Confluent cultures were maintained for 48 hr under varying oxygen tensions ranging from 135 to 18 mmHg. A reduction in basic fibroblast growth factor levels was observed in the cell lysates and extracellular matrix from retinal microvascular endothelial cell, retinal microvascular pericyte and retinal pigment epithelial cell cultures when the oxygen tension of the medium was reduced from 135 to 18 mmHg. Levels of basic fibroblast growth factor in conditioned media from microvascular endothelial and retinal pigment epithelial cell cultures also decreased when the oxygen tension of the medium was reduced from 135 to 18 mmHg. Total transforming-growth-factor-beta (and specifically isoforms 1 and 2) in the conditioned media from all three cell types was similarly modulated by oxygen i.e. it decreased as the oxygen tension of the medium was reduced from 135 to 18 mmHg. In contrast, the steady state messenger RNA levels for both basic fibroblast growth factor and transforming-growth-factor-beta 1 genes in RPE cells increased significantly when the oxygen tension of the medium was reduced from 135 to 18 mmHg. These results support the putative role of oxygen in influencing the balance of growth factors during the development of preretinal new vessels.
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In this study the activities of two lysosomal enzymes in retinal pigment epithelial (RPE) cells isolated from three regions of the human fundus were examined: the macula, the nasal midzone, and the periphery. The results obtained showed that the activities of acid phosphatase and cathepsin D were significantly higher in the RPE cells derived from the macular region when compared with those in the periphery. The values for the midzone appeared to be intermediate between the other two regions. Furthermore, the overall activity of both enzymes increased as a function of age.
Insulin-like growth factor I (IGF-I) and its associated binding proteins (IGFBPs) have been identified in retinal tissues but their precise cellular origin remains unclear. The aim of this study was to examine the ability of three retinal cell types (microvascular endothelial cells, pericytes, and pigment epithelial cells) and a non-retinal cell type (Tenon's fibroblasts) to produce IGF-I and cell specific IGFBPs in vitro. Using a radioimmunoassay we demonstrated that all four cell types produce IGF-I and that this production continued over a 72 hour period. In addition, western ligand blotting revealed that each cell type produced at least one IGFBP and that each cell type produced a different IGFBP profile. Endothelial cells produced a 24 kDa band only, pericytes produced both a 24 kDa and a 34 kDa band, retinal pigment epithelial cells produced a 38-41 kDa band, while fibroblasts produced both a 24 kDa and a 30 kDa band. Laser scanning densitometry demonstrated that in the majority of experiments the IGFBPs accumulated in the culture medium over a 72 hour period. Neither IGF-I nor IGFBPs were observed in cell lysates indicating de novo synthesis and secretion in vitro. These results suggest an autocrine/paracrine function for IGF-I and its associated binding proteins which may play a significant role in both retinal physiology and disease.
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This study compared the effects of vitreous gel, retrohyaloid fluid and subretinal fluid from diabetic and non-diabetic eyes on the proliferation and migration of retinal microvascular cells in vitro. Intraocular fluids were obtained from eyes undergoing repair of retinal detachment, due either to proliferative diabetic retinopathy or rhegmatogenous retinal detachment associated with a degree of proliferative vitreoretinopathy. The results demonstrated that the intraocular stimulatory activity for the proliferation of retinal microvascular endothelial cells varied between the different ocular compartments. The mitogenic and migrational activity in vitreous gel was greater than that of either the subretinal or retrohyaloid fluids of the same eye, and the activity of subretinal fluid was intermediate between that of the vitreous gel and the retrohyaloid fluid. There was no significant difference between the activities of the samples from diabetic and non-diabetic eyes.
The purpose of the present study was to examine whether impaired milk folate secretion during maternal iron deficiency is due to an altered flux of folates within the mammary secretory cell. Specifically we sought to determine whether the folate substrates of methionine synthase and the products of folylpolyglutamate synthetase are altered during iron deficiency in vivo. Rats were fed diets containing 0.5, 2.0 or 7.0 mg/kg folate and 8(Fe-) or 250(Fe+)mg/kg Fe throughout gestation and lactation. On day 17 of lactation dams were milked and killed. The concentration of reduced, methylated (5-CH3-H4), nonmethylated short and long chain forms of folate in milk were determined using a differential microbiological technique. Total mean milk folate concentrations among Fe- dams fed 2.0 and 7.0 mg/kg folate were half that of Fe+ dams fed 2.0 and 7.0 mg/kg folate. Despite this, the relative proportion of reduced, 5-CH3-H4, short and long chain folates did not differ in milk from Fe+ or Fe- dams. Approximately 75% of milk folates were methylated. Only Fe+ dams fed 7.0 mg/kg folate produced milk containing significant quantities of incompletely reduced folates. In conclusion, activity of the mammary epithelial cell enzymes methionine synthase and folylpolyglutamate synthetase in vivo, are unaffected by iron deficiency and therefore are not responsible for the dramatic reduction in milk folate secretion.
Microvascular fragments and pure cultures of either retinal microvascular endothelial cells, retinal pericytes or Tenon's capsule fibroblasts were grown on a gas permeable substrate while exposed to varying oxygen concentrations (5, 10, 20, 40 and 95% oxygen). For all three cell types cell proliferation was greatest under the lowest oxygen concentration and decreased as the oxygen concentration increased. The decrease in the proliferative ability of cells exposed to the higher oxygen concentrations could be reversed if the cells were returned to a normoxic environment. Endothelial cells were the most sensitive to changes in oxygen tensions showing a proliferative response after 24 hr exposure as opposed to 48 hr for pericytes and fibroblasts. These results suggest a direct mechanism by which the intra-vitreal and intra-retinal oxygen tension may influence both the development of preretinal new vessels (in response to retinal ischaemia) and also the regression of neovascularization following scatter photocoagulation or vitrectomy.
Allergic bronchopulmonary aspergillosis has been recognized in association with cystic fibrosis in children since 1965. Since then, however, there have been a paucity of reports of pediatric cystic fibrosis complicated by allergic bronchopulmonary aspergillosis, and, in most cases, these have been diagnosed retrospectively. A cluster of five acute cases seen during a 4-month period in a single cystic fibrosis center with a systemic illness and deterioration in respiratory status are described. In all five patients, reversible bronchoconstriction and infiltrative changes on x-ray films suggested the diagnosis. This was confirmed by the presence of (1) peripheral blood eosinophilia, (2) elevated total IgE and Aspergillus fumigatus-specific IgE, and (3) circulating serum precipitins against A fumigatus in all cases. All children tested had positive type 1 immediate hypersensitivity to skin tests for A fumigatus, in sputum eosinophilia, and Aspergillus cultured from sputum. Only three of five children were previously noted to be atopic and none had severe advanced suppurative lung disease. All children had previously received bronchodilator therapy and appropriate antibiotics. Following treatment with corticosteroids, acute symptoms and radiologic changes resolved for 1 to 5 months. To date, no children have had recurrence of their allergic bronchopulmonary aspergillosis while receiving alternate-day steroid treatment for 6 months.
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