Biomedical subjects

Paul Hiscott

Publications and source records attributed to Paul Hiscott.

24 records · Page 2Linked to original sources

PubMed2003

Monosomy 3 in uveal melanoma: correlation with clinical and histologic predictors of survival.

PURPOSE: To correlate monosomy 3 in uveal melanoma with clinical and histologic prognostic variables and death caused by metastatic disease. METHODS: Loss of heterozygosity (LOH) on chromosome 3 was investigated by PCR-based microsatellite analysis in 105 tumors and related to large basal tumor diameter (LBD), ciliary body (CB) involvement, tumor cell type, periodic acid-Schiff (PAS)-positive loops, and death related to metastatic disease. A model relating monosomy 3 to these was created with forward-stepwise logistic regression and used to derive a prognostic index. RESULTS: Monosomy 3 occurred in 54 (51%) tumors and regional chromosome 3 LOH in another six (6%) tumors. Monosomy 3 was associated with epithelioid cells (chi(2) test, P < 0.001), PAS-positive loops (chi(2), P = 0.001), LBD (Mann-Whitney test, P = 0.002), CB involvement (chi(2) test, P = 0.008), and metastasis-related death (log rank analysis, P = 0.0003). The regression coefficients indicated that epithelioid histology was 15 times as influential with each millimeter of increase in LBD. A prognostic score was derived: one point for each LBD category (<7.4, 7.5-12.4, 12.5-17.4, and >17.4 mm) and three points for epithelioid histology. The prevalence of monosomy 3 increased with score, from 0% in 18 tumors scoring less than 4 to 95% in 21 tumors scoring 7. CONCLUSIONS: Monosomy 3 correlates with survival but can be predicted only in patients with large epithelioid tumors. The absence of monosomy 3 is predictable only in patients who have small, spindle-cell tumors. In most patients, prediction of monosomy 3 according to tumor size and histology is unreliable.

Adult↗

PubMed2002

Protein localization in the human eye and genetic screen of opticin.

The opticin (OPTC) gene encodes a protein that is a member of the small leucine-rich repeat protein (SLRP) family. OPTC is located on chromosome 1q31-q32 within an age-related macular degeneration (AMD) susceptibility locus. We have developed an affinity-purified N-terminal anti-opticin antibody and used it to examine opticin expression in human eye tissues. The antibody was also used for opticin protein localization in human eye sections. Immunoblots of human eye tissues detected a predominant band of approximately 62 kDa in size in iris, trabecular meshwork/ciliary body, retina, vitreous, and optic nerve. Immunohistochemical experiments revealed that opticin is specifically localized in human cornea, iris, ciliary body, vitreous, choroid and retina. Due to opticin's protein profile in the eye, we have also screened OPTC for mutations in individuals with primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG) or AMD. We identified four sequence variations, all of which were observed in normal controls except for the Arg229Cys change. Three amino acid substitutions (Ile182Thr, Arg229Cys and Arg325Trp) were in residues conserved in dog, mouse, pig and human. The Arg229Cys alteration was present in a homozygous state in one individual with neovascular AMD. Examination of the other AMD afflicted family members showed that the OPTC Arg229Cys variant did not segregate with the disorder within the family. The protein localization pattern of opticin and our preliminary screen of AMD patients suggest that a larger AMD patient screen may be warranted.

Aged↗

PubMed2002

Noncontiguous tumor recurrence of posterior uveal melanoma after transscleral local resection.

OBJECTIVE: To describe the clinical and histopathologic features of noncontiguous tumor recurrence after transscleral local resection of posterior uveal melanoma. METHODS: Chart review was performed to identify patients with noncontiguous tumor recurrences from a series of 494 consecutive patients treated with transscleral local resection for uveal melanoma. The clinical and histopathologic features of noncontiguous tumor recurrences were studied. RESULTS: Nine cases were identified, for an estimated incidence of 1.8%. The average diameter of the primary tumors was 16.1 mm (range, 9-22 mm) and the average thickness was 9.8 mm (range, 6-14 mm). Noncontiguous tumor recurrences were solitary in 7 cases and multiple in 2 cases, with an average diameter of 5.8 mm (range, 3.0-9.5 mm). Eight of the 9 patients developed tumor recurrences at multiple intraocular sites. With a mean follow-up of 82.1 months (range, 22-171 months), 7 patients had a final visual acuity of counting fingers or worse, and there were 3 deaths from metastatic disease. CONCLUSIONS: Noncontiguous tumor recurrence after local resection appears to be related to intraocular dissemination from the primary tumor, either through the natural course of the disease or secondary to surgical manipulation. Eyes with large primary uveal melanomas developing noncontiguous tumor recurrence have a high risk of developing tumor spread to multiple intraocular sites, and aggressive treatment is warranted.

Adult↗

PubMed2002

Corneal stromal cells (keratocytes) express thrombospondins 2 and 3 in wound repair phenotype.

Members of the thrombospondin (TSP) family of proteins have been implicated in wound healing. The cells of the corneal stroma (keratocytes) are capable of synthesising TSP-1 in a wound repair phenotype, but do not appear to produce the protein in the normal human adult cornea. We employed reverse-transcriptase polymerase chain reaction (RT-PCR) to determine whether human corneal stromal cells can express TSPs other than TSP-1. Cultured keratocytes contained messenger RNA (mRNA) for TSP-2 and TSP-3 (in addition to TSP-1), but not for TSP-4 or cartilage oligomeric matrix protein (COMP; TSP-5). Keratocytes in the normal cornea contained mRNA for TSP-1 but not for other TSPs. The distribution of keratocyte TSP-2 and TSP-3 immunoreactivity had some similarities to that of TSP-1 and, like TSP-1, neither protein could be detected in the cells of the normal corneal stroma. The observations suggest that keratocytes in wound repair phenotype produce TSP-2 and TSP-3 in addition to TSP-1. TSPs may play a pivotal role in corneal stromal repair and, since TSP-1 and TSP-2 have anti-angiogenic properties, may also have a function in regulating the avascularity of the central cornea.

Cells, Cultured↗

PubMed2002

Direct comparison of the migration of three cell types involved in epiretinal membrane formation.

PURPOSE: The purpose of the present study was to develop an accurate and sensitive migration assay to compare the migratory capabilities of retinal pigment epithelial (RPE) cells, retinal glial (RG) cells, and fibroblasts (the cell types crucial in epiretinal membrane [ERM] formation) under identical microenvironmental conditions and thus to identify potential target areas in ERM management. METHODS: Cultured bovine RPE and RG cells and scleral fibroblasts (SFs) in both single and mixed cell type populations were induced to migrate in modified 48-well Boyden chambers. The labels used to distinguish between the cell types were latex microspheres and carmine particles. The chemoattractants used were fibronectin and PDGF, both of which are associated with epiretinal membrane development. RESULTS: When migrating independently, all three cell types showed a positive response to fibronectin at an optimal concentration of 10 microg/mL. The RG cells migrated in a significantly greater number than the RPE cells (P < 0.05), but the differences in number of migrating cells between RG cells and SFs and RPE cells and SFs were not significant. When the cells were labeled and migrating together, it became clear that the RG cells consistently migrated in a higher number than the SFs (P <or= 0.001) and both the SFs and RG cells showed a greater migratory response than the RPE cells (P <or= 0.01). CONCLUSIONS: The mixed cell migration (MCM) test system is a simple and useful assay to distinguish between the migratory responses of different cell types in the same microenvironment. It has highlighted the pronounced migratory response of RG cells to standard chemoattractants and has cast some level of doubt that, in comparative migratory terms, RPE cells are particularly good responders.

Animals↗

PubMedDate not supplied

Edible mushroom (Agaricus bisporus) lectin inhibits human retinal pigment epithelial cell proliferation in vitro.

The retinal pigment epithelium (RPE) plays a major role in the development of the anomalous retinal scarring response termed proliferative vitreoretinopathy. The present study was undertaken to investigate whether agaricus bisporus lectin inhibited human RPE proliferation in vitro. Fluorescein isothiocyanate-labeled agaricus bisporus lectin was used to study binding of lectin to cultured human RPE. The effect of a 24-hour exposure of agaricus bisporus lectin on RPE proliferation was measured using (methyl-3H)-thymidine incorporation into DNA. Toxicity studies were assessed using morphologic evaluation, trypan blue exclusion, and a cell viability assay. Agaricus bisporus lectin bound to RPE cells and was inhibited by preincubation of lectin with asialomucin. Agaricus bisporus lectin caused a dose-dependent inhibition of RPE proliferation (one-way ANOVA, F = 94.470, p < 0.001) that was partially reversible on removal of the lectin. Compared with controls, cells remained viable and no morphological changes or trypan blue staining was noted in RPE exposed to agaricus bisporus lectin. Human RPE binds agaricus bisporus lectin and inhibits proliferation without apparent cytotoxicity. It therefore merits consideration as a potential antiproliferative agent in the prevention and treatment of proliferative vitreoretinopathy and other nonocular anomalous wound healing processes.

Cell Division↗