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Biomedical subjects

W S Foulds

Publications and source records attributed to W S Foulds.

At least 19 recordsLinked to original sources

Flash and pattern reversal visual evoked responses in normal and demented elderly.

P1 and P2 components of visual evoked responses (VERs) to flash stimuli were compared between patients diagnosed as suffering from Senile Dementia of the Alzheimer Type (AD) and elderly controls. Additionally the P100 component of the VER to pattern reversal stimuli at high and low contrast and using large and small check patterns was compared. Significant differences between moderate AD patients and the normal elderly were found for the P2 component of the flash stimulus and for the P100 component of the high spatial frequency pattern reversal stimuli at low contrast. These findings suggest a deficit in primary visual processing and a selective deficit in secondary visual processing in moderate cases of dementia. This indicates that visual processing capacities of AD patients decline as the disease progresses in line with the continual degeneration of neuronal populations involved with vision.

Aged

The uses and limitations of intraocular biopsy.

Based upon the author's considerable experience of trans-scleral resection of malignant melanoma of the choroid, a technique has been developed for the biopsy of tissues of the posterior segment of the eye. Its use in the management of atypical malignancy posing diagnostic difficulty and in the investigation of selected case of acute retinal necrosis, uveitis and retinal pigment epitheliopathy is described. In 34 trans-scleral biopsies of choroid, RPE and in some cases, retina, an adverse result occurred in only one case, this it was thought being due to not including pars plana vitrectomy as part of the biopsy technique. Pars plana vitrectomy is now regarded as an integral part of this form of biopsy.

Biopsy

Analysis of mitochondrial DNA in Leber's hereditary optic neuropathy.

Twenty-eight patients from 25 maternal lineages with Leber's hereditary optic neuropathy (LHON) were investigated by restriction enzyme analysis for the presence or absence of the point mutation described by Wallace et al. The mutation was identified in 18 of 25 (72%) families with LHON. This provides further evidence that this mutation is present in the majority of patients with LHON. In 19 of these families with LHON, additional analysis using sequencing, oligonucleotide probing, and competitive oligonucleotide priming of PCR products was performed. In 14 cases with the site loss the point mutation was present, and five without the site loss had the wild type sequence in this region.

DNA, Mitochondrial

Specific radioimmunoassay to investigate rod outer segment phagocytosis by retinal pigment epithelium in vitro.

A sensitive radioimmunoassay has been developed which allows rapid quantitation of rod outer segment (ROS) phagocytosis by retinal pigment epithelial (RPE) explants in vitro. It involves the use of an antiopsin antiserum, in conjunction with 125I-protein A as a second antibody, and utilizes permeabilization with ethanol to distinguish between the binding and ingestion phases of phagocytosis. This procedure will be used in the future to investigate potential regulatory factors of ROS phagocytosis by retinal pigment epithelium and to evaluate animal models of retinal degeneration.

Animals

D-[3H]galactose incorporation into glycogen in retinal cone cells.

Previous studies have shown that bovine retinas incubated with [3H]galactose incorporated it, unmodified, into large molecules. Light and electron microscope autoradiography showed a significant proportion of the label to be in cone inner segments, and pulse-chase studies showed it was subsequently transported to the synaptic pedicles. In this report, evidence is presented to show that the galactose-labelled macromolecules are resistant to hydrolysis by proteolytic enzymes, testicular hyaluronidase, chondroitinase ABC, beta-glucosidase and beta-glucuronidase, but are readily degraded by alpha-amylase and beta-galactosidase, and to a lesser extent by beta-amylase. Treatment with alpha-amylase also leads to specific removal of radioactivity from cone inner segments and pedicles, as judged by light-microscopic autoradiography. These studies appear to indicate that the cone-specific galactose label is in glycogen or glycogen-like molecules.

Animals

Tumour-associated retinal pigment epitheliopathy.

Choroidal tumours are associated with several degenerative changes in the overlying tissues, which can be called 'Tumour-Associated Retinal Pigment Epitheliopathy (TARPE)'. These changes include (i) proliferation, detachment, atrophy, and metaplasia of the retinal pigment epithelium, (ii) the accumulation of hard and soft drusen and basal laminar deposits in Bruch's membrane, (iii) disorganisation of the choriocapillaris, (iv) atrophy, cystic degeneration and detachment of the retina. The changes at the chorio-retinal interface are clinically relevant because they can exacerbate visual loss. In addition, they can be misinterpreted on ophthalmoscopy and fluorescein angiography. An amelanotic choroidal tumour may appear to be pigmented on ophthalmoscopy because of lipofuscin and melanin accumulation overlying the tumour. The hyperfluorescence associated with pigmented choroidal melanomas is more likely to be related to degenerative changes in the retinal pigment epithelium than to dye leakage from abnormal tumour vessels.

Choroid

Brightness discrimination and contrast sensitivity in chronic glaucoma--a clinical study.

The visual acuity, the difference in sensitivity of the two eyes to light (brightness ratio), and contrast sensitivity were assessed in 28 patients with chronic open angle glaucoma and compared with those of 41 normal controls of similar ages and visual acuity. The results obtained were related to the results of Tübingen visual field analysis in patients with glaucoma. Twenty-four of the 28 glaucoma patients (86%) had a significant disparity in brightness ratio between the two eyes. This was found to match the frequency of visual field loss. Moreover, there was a significant relationship between the interocular differences in brightness sense and the difference in the degree of visual field loss between the two eyes. Of the glaucoma patients 39% had sum contrast sensitivities outside the normal range for age-matched normal controls. No significant correlation was found between the interocular difference in brightness sense and the visual acuity or the interocular difference in sum contrast sensitivity. It is concluded that, in the presence of a normal visual acuity, the brightness ratio test warrants evaluation as a potential screening test for chronic open angle glaucoma.

Adult

Herpes simplex virus 1 infection upregulates stress protein expression in cultured retinal neurons.

The production of a 57K stress protein (StrP) after herpes simplex virus type 1 (HSV-1) infection was examined in cultured neonatal rat retinal cells. StrP expression in individual cells was identified using a monoclonal antibody, TI56. Indirect immunofluorescence of uninfected retinal cultures showed that approximately 40% of cells expressed neurofilament (NF+) and 5% expressed a low level of StrP. Following HSV infection the proportion of NF+ cells decreased while the proportion of StrP positive cells became greater and the intensity of staining increased. The number of cells labelled with a polyclonal anti-HSV antibody increased with time after infection. Retinal neurons in culture can be infected with HSV, after which StrP expression is significantly upregulated.

Animals

Effect of glycoconjugates on rod outer segment phagocytosis by retinal pigment epithelial explants in vitro assessed by a specific double radioimmunoassay procedure.

Rod outer segment (ROS) phagocytosis by explanted bovine retinal pigment epithelium (RPE) was evaluated by a procedure using an indirect double radioimmunoassay which distinguished between ROS attached to the RPE cell surface and those which had been ingested. This approach has been used to investigate the effect of a variety of glycoconjugates on the phagocytic process. Inclusion of the glycosaminoglycans (GAGs) chondroitin sulphate type-A (CS-A) and type-C (CS-C), hyaluronic acid (HA) or dermatan sulphate (DS) in the incubation medium significantly inhibited the ingestion phase of ROS phagocytosis, whereas the binding phase was inhibited to a lesser extent. The interphotoreceptor matrix (IPM), containing these GAGs as part of proteoglycans, also had an inhibitory effect on phagocytosis. The free monosaccharides mannose, fucose and galactose all stimulated the ingestion of ROS by RPE cells. These findings support the suggestion that glycoconjugates may have a physiological role in the photoreceptor renewal process.

Animals

Response of cultured Müller cells to heat shock--an immunocytochemical study of heat shock and intermediate filament proteins in response to temperature elevation.

Müller cells from adult rabbit retina were cultured at normal (37 degrees C) temperature and under heat shock conditions (42-43 degrees C) for either 1.5 hr or 4 hr. The presence of heat shock proteins of three different molecular weights, and of vimentin, was identified by the use of monoclonal antibodies and of GFAP by a suitable polyclonal antibody coupled in each instance with immunofluorescence microscopy or immuno-electron microscopy. Heat shock conditions resulted in the expression of HSP of molecular weights in the ranges 57-61 kD, 68 kD and 90 kD. The high level of expression of GFAP in unshocked Müller cell cultures (80-90% of cells) was reduced after 1.5 hr of heat shock to 20-30% of cells, and after 4 hr to only 5%. Although the expression of vimentin (90% of untreated cells) was only slightly reduced by heat shock (60-80% of cells) the intracellular staining pattern of vimentin was greatly altered by heat shock. Changes in the expression of HSP, GFAP and vimentin can all be regarded as part of the Müller cell response to heat shock conditions.

Animals

Abetalipoproteinaemia in adults: role of vitamin therapy.

The retinal and neurological complications of abetalipoproteinaemia may be preventable by replacing vitamins A and E from an early age, but their role in adult presentations is less clear. Two adult females with abetalipoproteinaemia have received 8 and 10 years respectively of replacement therapy with vitamins A, E and linoleic acid. In Case 1, visual function improved objectively on commencing therapy but has subsequently deteriorated and her neuropathy has slowly progressed. The rate of progression of neurological impairment in Case 2 was slowed but not halted by therapy, and her severe visual disturbance was unaffected. Replacement by fat soluble vitamins has only a limited role in the management of abetalipoproteinaemia once irreversible neurological/retinal damage has occurred.

Abetalipoproteinemia

Detection of haematoporphyrin derivative and haematoporphyrin excited states in cell environments.

The photosensitiser currently used in the photodynamic therapy of cancer is haematoporphyrin derivative. Pulsed laser studies of this material and also of the "parent" molecule haematoporphyrin in polyoma-transformed fibroblast cells have now been studied. We report, for the first time, the observation of the triplet absorption of these sensitisers in cells. The corresponding triplet-triplet spectra are red shifted compared to aqueous buffer, lambda(max) 420 nm shifts to 460 nm. We also report our failure to observe singlet oxygen from the cells even though the triplet state can be seen to interact with the oxygen and even though singlet oxygen can be readily detected with the same sensitisers bound to serum albumin.

Cell Line

B-lymphocytes from melanoma patients and normal individuals react with melanoma cells but also with irrelevant antigens.

Peripheral B-lymphocytes of 13 patients with uveal melanoma and of 5 healthy individuals were transformed with Epstein-Barr virus (EBV). The reactivity of these transformed cells with autologous or allogeneic melanoma cells and lymphocytes was measured by the enzyme-linked immunosorbent assay (ELISA). Antigens which are neither self nor common environmental antigens (i.e., plant protoplasts, schistosome antigen and keyhole limpet haemocyanin) were used for controls. Lymphocyte reactivity with all types of antigen was apparent both in patients with uveal melanoma and in normal controls. The response detected by the techniques available is likely to reflect antibody multispecificity leading to mis-identification of irrelevant antigens.

Animals

Comparative ultrastructural study of rabbit Müller cells in vitro and in situ.

The ultrastructural appearance of cultured rabbit glial cells (putative Müller cells) has been compared with that of rabbit Müller cells in situ. Electron microscopy disclosed that the cultured cells had a basement membrane comparable to the inner limiting membrane of the retina and that villous processes adjacent to zonulae adherentes were reminiscent of fibre baskets and the outer limiting membrane. Cultured cells showed apico-basal polarisation in specimens from early passages. It was noted however that cultured cells showed a number of features which were different from normal Müller cells in situ. These included prominent rough endoplasmic reticulum, sparse smooth endoplasmic reticulum and relatively electron lucent cytoplasmic matrices. These findings resembled the appearances found in proliferating Müller cells in the human eye. The ultrastructural differences noted in the cultured Müller cells suggest that the cultured cells are in an active form.

Actin Cytoskeleton