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Biomedical subjects

F A Billson

Publications and source records attributed to F A Billson.

At least 37 records · Page 2Linked to original sources

Human retinoblastoma: in vitro differentiation and immunoglobulin superfamily antigen modulation by retinoic acid.

Suspension and attachment cultures of Y79 human retinoblastoma cells were treated with all-trans retinoic acid (RA) for up to 10 days to assess its effect on growth and cell-surface expression of immunoglobulin superfamily antigens MHC class I and class II, ICAM-1, NCAM and Thy1. RA up to 10 microM induced growth inhibition, and marked morphological differentiation with extension of prominent processes resembling neurites was seen in attachment cultures. However, above 10 microM RA produced extensive cell death. We also observed increased cell-surface expression of MHC class I, ICAM-1, NCAM and Thy1 on Y79 cells treated with 10 microM over 10 days; constitutive MHC class II expression was not apparent, nor did RA treatment appear to induce Y79 cells to express MHC class immunoreactivity. The up-modulation of cell-adhesion molecules (NCAM, ICAM-1 and Thy1) and immune recognition molecules (NCAM, ICAM-1 and MHC class I), associated with reduced growth and tumour cell differentiation, suggests that RA may have a potential role in regulating the growth and development of retinoblastoma tumours.

Adjuvants, Immunologic↗

Choroidal melanoma: a review of the experience of the Sydney Eye Hospital Professorial Unit 1979-1995.

PURPOSE: This study examines 90 patients presenting with choroidal or ciliochoroidal melanoma to the Professorial Unit at the Sydney Eye Hospital. The indications for treatment, and the outcome for the eye and vision are presented together with an account of mortality and the incidence of metastases. METHODS: A retrospective analysis of 90 choroidal melanoma patients managed by one surgeon over a 16-year period was undertaken. Initial findings, investigations performed, incidence of metastatic disease, treatment received and complication rates and mortality, where applicable, were recorded. RESULTS: The group was followed for an average of 64 months (range, 5-172 months). Primary treatment was with either iodine125 (125I) brachytherapy, local excision or enucleation. Radiation retinopathy was prominent in 125I cases resulting in poor visual acuity when the tumour resided in the posterior pole. Local excision even of large tumours was effective particularly if peripheral. Overall metastatic disease was seen in 11% with 5-year survival rates for the metastatic group being 10%. Prognosis after diagnosis of metastases was poor. CONCLUSIONS: Specific therapy for choroidal melanoma must relate to the size and location of the tumour at the time of diagnosis. Visual outcome relates directly to the proximity of the tumour to the optic nerve and fovea. Metastatic disease latency can be prolonged; therefore caution about prognosis is required long after therapy is given. The 5-year survival is encouraging with all forms of therapy. However, as the natural history of ocular melanoma is variable and not fully delineated it is important to monitor the effects of conservative therapy. Further long-term survival data is required to distinguish whether one form of treatment is advantageous over the others, although case-control studies are difficult for ethical and practical reasons. In this regard the Collaborative Ocular Melanoma Study (COMS) will provide further evidence for the safety and efficacy of conservative therapy with brachytherapy compared to enucleation.

Adult↗

Effect of human vitreous and hyalocyte-derived factors on vascular endothelial cell growth.

PURPOSE: In the present study we have examined the effects of human vitreous and hyalocyte-conditioned medium on human umbilical vein endothelial cells (HUVEC). METHODS: Human umbilical vein endothelial cells were cultured and treated in quadruplicate with human vitreous and hyalocyte-conditioned medium at different concentrations. Cell numbers were counted on days 1, 3, 5 and 7. Morphological changes and the viability of cells after treatment were also monitored. RESULTS: The results indicate that both human vitreous and hyalocyte-conditioned medium inhibit proliferation and reduce the viability of HUVEC in vitro. These inhibitory effects were dose- and time-dependent. CONCLUSIONS: The observations suggest that human hyalocytes and vitreous contain anti-angiogenic factors that influence vascular endothelial cell-growth. These results, combined with those of previous studies, may yield important information about the functional role of vitreous and hyalocytes in intraocular vascular regression.

Adult↗

Development of microglial topography in human retina.

The development of microglial topography in wholemounts of human retina has been examined in the age range 10-25 weeks gestation (WG) using histochemistry and immunohistochemistry for CD45 and major histocompatibility complex class II antigens. Microglia were present in three planes corresponding to the developing nerve fibre layer/ganglion cell layer, the inner plexiform layer and the outer plexiform layer. Distribution patterns of cells through the retinal thickness and across the retinal surface area varied with gestational age. Microglia were elongated in superficial retina, large and ramified in the middle plane, and small, rounded and less ramified in deep retina. Intensely labeled, rounded profiles seen at the pars caeca of the ciliary processes, the retinal margin and at the optic disc may represent precursors of some retinal microglia. At 10 WG, the highest densities of microglia were present in middle and deep retina in the far periphery and at the retinal margin, with few superficial microglia evident centrally at the optic disc. At 14 WG, high densities of microglia were apparent superficially at the optic disc; microglia of middle and deep retina were distributed at more central locations although continuing to concentrate in the retinal periphery. Microglia appear to migrate into the developing human retina from two mains sources, the retinal margin and the optic disc, most likely originating from the blood vessels of the ciliary body and iris, and the retinal vasculature, respectively. The data suggest that the development of microglial topography occurs in two phases, an early phase occurring prior to vascularization, and a late phase associated with the development of the retinal vasculature.

Age Factors↗

Exudative macular degeneration and intravitreal triamcinolone. A pilot study.

PURPOSE: To study the efficacy of the anti-inflammatory agent triamcinolone (Kenacort A-40) in patients with exudative age-related macular degeneration and subfoveal and juxtafoveal choroidal new vessels, considered unsuitable for laser photocoagulation. METHOD: Thirty eyes of 28 patients were treated with intravitreal injection of triamcinolone. The subsequent visual acuity (VA) of treated eyes was compared with published VA outcomes of untreated eyes. Patients were classified into three types according to their responses to treatment. RESULTS: Within two weeks of receiving treatment, exudation decreased and vision improved in the majority of Types I and II patients (87%), the trend continuing in longer term follow-up. The overall VA outcome for treated eyes was significantly better than published VA data for untreated exudative macular lesions. CONCLUSIONS: The preliminary results are encouraging and no serious side effects of a single injection of triamcinolone have been detected in patients followed for up to 18 months. The treatment should, however, continue to be regarded as unproven and only administered in the context of a prospective, case-controlled clinical trial.

Aged↗

Induction of apoptosis by sodium butyrate in the human Y-79 retinoblastoma cell line.

The mode of cell death induced in the Y-79 human retinoblastoma cell line by sodium butyrate (SB), a short-chain fatty acid with potent inhibitory effects on the growth of many transformed cell lines, was investigated by fluorescence and transmission electron microscopy, agarose gel electrophoresis, and metabolic studies. While SB (< 1 mM) resulted in marked morphological differentiation, higher concentrations (1-4 mM) induced predominantly apoptotic involution in Y-79 in a concentration-dependent fashion after a latent period of 24 h. Dying cells displayed the characteristic morphology of apoptosis accompanied by DNA laddering with agarose gel electrophoresis. Extensive cell necrosis was apparent with 0.5 M SB. Induction of apoptosis and DNA laddering by SB was reduced by putative inhibitors of RNA and protein synthesis, but not putative endonuclease inhibitors. These results are important for understanding the mode of action of sodium butyrate as a potential cancer chemotherapeutic agent.

Apoptosis↗

Hydrolases of anterior segment tissues in the normal human, pig and rat eye: a comparative study.

The distributions of the hydrolases acid and alkaline phosphatase (AP and ALP), N-acetyl-beta-D-glucosaminidase (NAG), beta-glucuronidase (beta-Gluc), beta-galactosidase (beta-Gal), non-specific esterase (UE), dipeptidylpeptidases II and IV (DPPII and DPPIV), aminopeptidases M and A (APM and APA), and gamma-glutamyltransferase (GGT) were investigated in the human, pig and Lewis rat normal anterior segment by histochemical methods. The distribution of the above hydrolases, particularly that of proteases, varied between ocular tissues and between the three species. Lysosomal hydrolases together with GGT and ALP were consistently active in the corneal epithelium, stroma and endothelium in all three species; the corneal distribution and activity of beta-Gal, APM, APA and DPPIV, however, displayed interspecies variation. The angular tissues showed similarities for most hydrolases with the exceptions of beta-Gal, UE, APM, APA and DPPIV. In all eyes examined strong ciliary epithelial activity for AP, beta-Gal, UE, GGT and ALP was observed in the pars plicata; only the pig eye also displayed strong DPPIV activity in this area. Regional differences in hydrolase distribution in the iris were observed in all species. A post-mortem freezing delay of longer than 24 h resulted in a decrease in hydrolase activity.

Aged↗

Modulation of MHC class II expression in the absence of lymphocytic infiltrates in Alzheimer's retinae.

This study describes the expression of MHC class II antigens in retinal flat mounts from normal donors and patients with Alzheimer's disease (AD). We confirm previous observations of MHC class II immunoreactivity on microglia in normal retinae, while observing insignificant levels of reactivity on endothelial cells (EC). A significantly increased level of MHC class II expression was detected in AD retinae. This increased immunoreactivity was found to occur in the absence of lymphocytic infiltrates, suggesting that the pathogenesis of AD in the retina may be distinct from that reported to occur in some regions of the brain. MHC class II expression, measured using computerized optical densitometry, appeared to be increased principally as a result of induced MHC class II immunoreactivity on EC. Ramified microglia and perivascular macrophages, although hypertrophied, appeared to show unchanged levels of MHC class II expression. These findings are consistent with earlier suggestions that both aberrant MHC class II expression and suppressor activity of resident macrophages may restrict immune responses.

Adult↗

Suppurative corneal ulceration in Bangladesh. A study of 142 cases examining the microbiological diagnosis, clinical and epidemiological features of bacterial and fungal keratitis.

Suppurative keratitis is an important preventable cause of blindness, particularly in the developing world. This study analyses 142 cases of suppurative keratitis referred to Chittagong Eye Infirmary Bangladesh. Some 53.5% of cases were bacterial and 35.9% were fungal. The five most common pathogens were: Pseudomonas sp. 24%, Streptococcus pneumoniae 17%, Aspergillus sp. 13%, Fusarium sp. 7% and Curvularia sp. 6%. Gram stain and culture results were consistent in 62.6% of cases. Previous antibiotic treatment was a significant factor for failure of culture isolation and less so for Gram stain failure. On Gram stain, 55.9% of pseudomonal cases were missed, but only 2% of fungal cases were missed. Over all, Gram stain had a sensitivity of 62% and positive predictive value of 84% for bacterial cases, and 98% and 94% for fungal cases, respectively. Fungal ulcers were typically filamentous, but an antecedent history of trauma was not common. The most frequent injury was due to rice grains, but the inoculum appeared to be introduced during eye washing with contaminated water. Pseudomonal ulcers occurred most frequently in the monsoon season, and Fusarium cases were seen only in the hot, dry season.

Adolescent↗

Intermediate filament expression in human retinal macroglia. Histopathologic changes associated with age-related macular degeneration.

PURPOSE: Intermediate filament expression by retinal macroglia was studied in normal eyes, normal eyes of older subjects, and eyes of subjects with age-related macular degeneration (AMD), classified on the basis of histopathologic assessment of the retinal pigment epithelium (RPE), choroid, and donor age. METHODS: Adult human retinae (N = 43) were divided into three groups: normal (< 50 years of age, with normal RPE and choroid); normal eyes of older subjects (> 50 years with normal RPE and choroid); and eyes of subjects with AMD (> 50 years with histopathologic findings indicative of AMD), on the basis of histopathologic assessment of the RPE/choroid and donor age. Intermediate filament expression by retinal macroglia was studied in cryostat sections and in retinal flatmounts using avidin-biotin-peroxidase immunolabeling of antibodies to glial fibrillary acidic protein (GFAP) and vimentin. RESULTS. Analyses of immunohistochemically labeled retinal sections revealed similar distributions of vimentin reactivity in retinae of each group. Distributions of GFAP in normal and normal aged retinae were similar, but sections of AMD-affected retinae showed evidence of GFAP expression by Müller cells. In flatmounts, vimentin distribution was similar in the three groups, but GFAP labeling revealed hypertrophic astrocytes, which were absent from normal retinae, in 17% of aged retinae and 55% of AMD-affected retinae. Deeply penetrating, GFAP-positive processes were observed in 17%, 27%, and 55% of normal, normal aged, and AMD-affected retinae, respectively. CONCLUSIONS: Variation in GFAP and vimentin expression in retinal macroglia is affected by increasing age, and a distinctive variation of intermediate filament expression in retinal macroglia is associated with the pathogenesis of AMD.

Adolescent↗

Histochemical survey of the anterior segment of the normal human foetal and adult eye.

The distributions of the lysosomal enzymes [acid phosphatase (AP), N-acetyl-beta-D-glucosaminidase (NAG), beta-glucuronidase (beta-Gluc), beta-galactosidase (beta-Gal), dipeptidylpeptidase II (DPP II)] and of the membrane-bound proteases [aminopeptidase M (APM), aminopeptidase A (APA), gamma-glutamyltransferase (GGT), dipeptidylpeptidase IV (DPP IV)] were investigated in the normal human adult and foetal anterior segment by histochemical methods. The distribution of these hydrolases varied between ocular tissues. The most active enzymes in the adult corneal epithelium and endothelium were AP, beta-Gluc, NAG, beta-Gal and GGT; in the keratocytes, APM, APA, beta-Gluc and GGT predominated. The adult trabecular meshwork cells were stained by AP, beta-Gluc, NAG, APM, GGT, DPP II and DPP IV. The enzymes AP, beta-Gluc, APM and APA, however, displayed greater activity in the endothelium of Schlemm's canal. The adult ciliary epithelium stained strongly for all lysosomal hydrolases; GGT was the most active protease here. Differences in enzyme activity were noted in some tissues when foetal and adult anterior segments were compared. There appeared to be a decrease in the activity of some enzymes with age and post-mortem delay greater than 24 h. The function(s) of each enzyme and their possible roles in the respective tissues are discussed.

Aged↗

Long-term intraocular pressure control by trabeculectomy: a ten-year life table.

A retrospective study of 179 eyes in 127 patients who underwent trabeculectomy at Sydney Eye Hospital under the supervision of two surgeons between 1977 and 1982 was carried out. Survival analysis by life table method shows cumulative two, five, and 10 year success rates to be 78%, 70%, and 67% respectively, with mean duration of intraocular pressure control (IOP < 21 mmHg) being 88 months. Antiglaucoma medication improved the long-term survival significantly (Hazard Ratio of 0.49 and P = 0.01) so that when the definition for failure is taken as IOP > 20 mmHg while using medication, the two, five and 10 year success rates were 89%, 87% and 86% respectively. A rise in average intraocular pressure is seen between two weeks and three months after trabeculectomy. The improvement in long-term success rate with use of topical steroids was suggestive (Hazard Ratio of 0.69) but not conclusive (P = 0.21). No difference was found in survival comparing fornix versus limbal based flap technique.

Adolescent↗

Increased hydrolase activities in the human trabecular meshwork of glaucomatous eyes.

Alterations in the metabolic functions of trabecular meshwork (TM) cells are thought to be involved in the pathogenesis of primary open-angle glaucoma (POAG). In an investigation of this possibility, 30 trabeculectomy specimens from patients with POAG were examined histochemically for 11 lysosomal and membrane-bound enzymes. The patients ranged from 48 to 87 years in age. The degree of enzyme staining was compared with that of 15 age-matched controls obtained from an eye bank at less than 24 h after death. There was no history of eye disease in the controls. The enzymes examined were: dipeptidylpeptidases II and IV (DPPII and IV); beta-glucuronidase (beta-GLUC); acid-beta-galactosidase (s beta-GAL); N-acetyl-beta-D-glucosaminidase (NAG); nonspecific esterase (UE); acid phosphatase (SP); alkaline phosphatase (ALP); gamma-glutamyltransferase (GGT); and aminopeptidase A and M (APA and APM). Evaluation of the specimens was performed by two observers and by computer-aided optic densitometry. Results showed increased staining of SP, UE, GGT and APM in the pathological specimens as compared with the controls. SP and UE indicate phagocytic activity, APM is involved in collagen turnover and GGT participates in both drug detoxification and the breakdown of glutathione in the gamma-glutamyl cycle. Our observations show different hydrolase activities in the TM cells of human glaucomatous eyes as compared with normal values, suggesting that such metabolic differences may be related to the pathogenesis of POAG.

Aged↗

NADPH-diaphorase histochemistry reveals cone distributions in adult human retinae.

NADPH-diaphorase histochemistry was used to identify and analyse the topography of cones in adult human retinae (in the age range 44 to 68 years). Retinae were treated for NADPH-diaphorase reactivity, present in vascular walls, amacrine cells and cone and rod outer segments; a subpopulation of less intensely reactive profiles, morphologically resembling cones, possibly represents the blue cone population. Regularly spaced pairs of cones (one intensely labelled and one weakly labelled cone) were also apparent throughout the retina, and were most common along the horizontal meridian, particularly towards the periphery. The diameters and distributions of labelled cone outer segments were assessed using image analysis. Cone density in the adult retina ranged from 2000 per mm2 in the temporal periphery, to 82,000 to 120,000 per mm2 at the fovea centralis. Distribution patterns confirmed the presence of a cone streak, extending from the foveal region into nasal retina, but no evidence of superior-inferior asymmetry was detected.

Adult↗

Iodine-125 irradiation of choroidal melanoma: clinical experience from the Prince of Wales and Sydney Eye Hospitals.

We examined the records of 53 patients treated for choroidal melanoma between 1985 and 1989. The aim of this study was to assess the safety and short-term results of iodine-125 episcleral plaque therapy. There were 28 males and 25 females, aged 20 to 77 years (median 61 years), treated for single tumours with a median diameter of 9 mm (range 5 to 15 mm) and with a median thickness of 4 mm (range 2 to 10 mm). The plaques containing iodine-125 seeds were chosen according to tumour size: 10 mm (16 patients); 15 mm (36 patients); 20 mm (one patient). All patients are alive at last follow-up (median 1.3 years, range 4 months to 3.3 years). Four patients underwent enucleation for melanoma progression. Thirty patients have developed some type of complication (more than one complication occurred in the same eye in 12 patients): retinitis (19), optic neuropathy (7); cataract (4), rubeosis iridis (2). Overall, visual acuity deteriorated in 32 patients, remained stable in 12 patients and improved in 9 patients. Iodine-125 plaque therapy appears to offer patients good prospects of tumour control and preservation of useful vision.

Adult↗