Search PubMed⌕ Search

Biomedical subjects

C Sheridan

Publications and source records attributed to C Sheridan.

At least 19 recordsLinked to original sources
PubMed2005

Polyurethanes as potential substrates for sub-retinal retinal pigment epithelial cell transplantation.

Transplantation of cultured retinal pigment epithelial (RPE) cells under the failing macular is a potential treatment for age related macular degeneration. An important step in the development of this procedure is the identification of a suitable membrane on which to grow and transplant the cells. This paper evaluates the potential of using polyurethanes in this application since they possess several of the required properties, such as, flexibility, robustness, biostability and good biocompatiblilty although their hydrophobicity can limit cell adhesion. Three commercially available polyether urethanes (Pellethane, Tecoflex and Zytar) were evaluated in terms of their wettability using dynamic contact angle analysis and their ability to support a monolayer of functioning RPE cells (ARPE-19) . Furthermore Pellethane and Tecoflex were treated with a simple air plasma treatment and analysed as above. In the "as received condition" only a few RPE cells attached to the Pellethane and Tecoflex and remained clumped. RPE cells grew to confluence on the Zytar substrate by 7 days without further surface modification. Air gas plasma treatment of both Pellethane and Tecoflex increased the wettability of the surfaces and this resulted in the growth of a monolayer of well-spread RPE cells on both materials. Morphologically these cells grew with a normal 'cobblestone' phenotype. These results demonstrate the potential of these polyurethanes for this application.

Cell Line↗
PubMed2003

Edible mushroom (Agaricus bisporus) lectin modulates human retinal pigment epithelial cell behaviour in vitro.

The retinal pigment epithelium (RPE) plays a major role in the development of proliferative vitreoretinopathy (PVR). In particular, RPE cells are implicated in generating the contraction forces seen. The present study was undertaken to investigate whether human RPE binds a lectin from the common edible mushroom, Agaricus bisporus, and to evaluate the effect of any binding on RPE-mediated matrix contraction in an in vitro model of PVR. Fluorescein isothiocyanate (FITC)-labelled Agaricus bisporus lectin (ABL) was used to study binding of lectin to normal retina, PVR scar tissue specimens and cultured human RPE. The effect of a 3-day exposure of ABL on human RPE-mediated contraction was evaluated using 2- and 3D RPE-populated collagen matrices. Effect of ABL on cell adhesion was measured using a collagen type I adhesion assay and determining the relative cellular attachment using absorbance readings. The normal RPE monolayer did not stain with FITC-ABL while PVR scar tissue stained intensely. Staining of in vitro RPE was characteristic but time-dependent. ABL caused a dose-dependent inhibition of RPE-mediated contraction of both 2D (one-way ANOVA, F = 7.94, p < 0.008) and 3D collagen matrices (one-way ANOVA, F = 164.955, p < 0.001). Pre-incubation of ABL with RPE in the 2D model caused a dramatic arrest of contraction (one-way ANOVA, F = 20.1, p < 0.001) that was due to a dose-dependent inhibition of adhesion (one-way ANOVA, F = 15.603, p < 0.001). Recovery of contraction was partially reversible on removal of ABL and was dependent on initial concentration of the lectin. ABL inhibits contraction and adhesion of human RPE cells in vitro without apparent cytotoxicity. It therefore deserves consideration as a potential therapeutic agent in the prevention and treatment of PVR and other non-ocular anomalous wound-healing processes.

Agaricus↗
PubMed2001

Do you need an ASP ASAP?

Is your organization looking at the possibility of using an application service provider (ASP)? If so, here are some things you should know about making that decision, selecting a provider, and negotiating a contract.

Cost Control↗
PubMed2000

Predictive value of proton magnetic resonance spectroscopy in pediatric closed head injury.

We studied 26 infants (1-18 months old) and 27 children (18 months or older) with acute nonaccidental (n = 21) or other forms (n = 32) of traumatic brain injury using clinical rating scales, a 15-point MRI scoring system, and occipital gray matter short-echo proton MRS. We compared the differences between the acutely determined variables (metabolite ratios and the presence of lactate) and 6- to 12-month outcomes. The metabolite ratios were abnormal (lower NAA/Cre or NAA/Cho; higher Cho/Cre) in patients with a poor outcome. Lactate was evident in 91% of infants and 80% of children with poor outcomes; none of the patients with a good outcome had lactate. At best, the clinical variables alone predicted the outcome in 77% of infants and 86% of children, and lactate alone predicted the outcome in 96% of infants and 96% of children. No further improvement in outcome prediction was observed when the lactate variable was combined with MRI ratios or clinical variables. The findings of spectral sampling in areas of brain not directly injured reflected the effects of global metabolic changes. Proton MRS provides objective data early after traumatic brain injury that can improve the ability to predict long-term neurologic outcome.

Aspartic Acid↗
PubMed2000

Influence of pigment content, intracellular calcium and cyclic AMP on the ability of human retinal pigment epithelial cells to contract collagen gels.

PURPOSE: The aim of the study was to determine to what extent collagen gel contraction could be reduced by calcium and calmodulin antagonists and agents that elevate cyclic AMP in order to develop a pharmacological approach to prevent/arrest RPE contraction of epiretinal membranes in proliferative vitreoretinopathy. We also explored a possible role of pigment in collagen gel contraction. METHOD: We measured RPE mediated contraction of 3D collagen gels in the presence and absence of the calcium and calmodulin antagonists TMB8, Verapamil and Tamoxifen and the cAMP elevating agents IBMX and Forskolin. The effect of pigment on collagen gel contraction was assessed by comparing gel contraction mediated by RPE cells re-pigmented with melanin with that mediated by unpigmented RPE. The effect of IBMX on RPE proliferation was assessed using a BrdU ELISA and the effects of IBMX on RPE cytoskeleton and cell shape were assessed using Actin and Cytokeratin immunocytochemistry. RESULTS: We report that both cAMP elevating agents and calcium and calmodulin antagonists reduce RPE mediated collagen gel contraction. Cyclic AMP elevation was more effective than a reduction in calcium in reducing contraction. There were no significant advantages in combining both approaches. The presence of melanin had no effect on gel contraction. Calcium antagonists and particularly agents which elevate cAMP caused RPE cells in collagen gels to extend fewer and shorter processes. cAMP elevation in particular caused RPE cells to become more rounded and develop arborized cell processes. Immunostaining for actin and cytokeratin revealed changes in cytoskeletal organisation in response to IBMX in that cells contained less actin than untreated cells and concentrated cytokeratins more centrally. CONCLUSION: We have identified two possible pharmacological approaches which may provide a new direction for preventing or slowing down the development of PVR.

1-Methyl-3-isobutylxanthine↗
PubMed1999

A video-based performance in noise test for measuring audio-visual disability in young school children: test development, with validation by trained teachers, parents and audiometry as relative standards for disability.

BACKGROUND: impaired ability to detect target sounds in noisy surroundings is a particular feature of children with a history of otitis media with effusion (OME). Children with current OME are also likely to experience difficulty in speech reception in classrooms where a high level of background noise has been recorded. No tests are currently available which are feasible in primary care and which objectively measure school-related disabilities. The effects of speech in noise and the extent to which this is offset by speech reading contribute important dimensions to disability. METHODS: a video-based speech reception test has been developed using the same principles in 227 English and 182 Danish 4-8 year-old children. Distribution data was collected for both language versions of the test. The test has been compared with audiometry and teacher and parents assessments to establish its validity. INTERPRETATION: there are no gold standards for audio-visual disability in current clinical use. The poor positive predictive value of audiometry for likely classroom functioning is a cause for concern, particularly in relation to inappropriate referral of children by primary care physicians.

Audiometry↗
PubMed1999

Matrix and the retinal pigment epithelium in proliferative retinal disease.

In their normal state, RPE cell are strongly adherent to Bruch's membrane. Certain pathological conditions such as retinal detachment cause an injury-type response (probably augmented or induced by the local accumulation of a variety of substances which modulate cell behaviour) in which RPE begin to dissociate from the membrane. This RPE-Bruch's membrane separation may be mediated by proteins with counter-adhesive properties and proteolytic enzymes, partly derived from the RPE themselves. Concomitant with the RPE disassociation, the cells begin to lose tertiary differentiation characteristics and gain macrophage-like features. When the "free" RPE arrive at the surface of the neuroretina, they may attach to or create a provisional matrix. Some of the cells adopt a fibroblast-like phenotype. This phenotype is similar to that of the dermal fibroblast during cutaneous wound repair and the fibroblastic RPE synthesise the types of matrix components found in healing skin wounds. Many of these molecules in turn further modulate the activities of the cells via several families of cell surface receptors, while the RPE continue to remodel the new matrix with a range of proteolytic enzymes. The resulting tissue (or membrane) has many of the features of a contractile scar and is the hallmark of the condition known as proliferative vitreoretinopathy (PVR). Thus the development of PVR, and the resulting tractional distortion of the neuroretina, appears to be dependent on RPE-matrix interactions. The interactions present a number of potential therapeutic targets for the management of the disorder.

Animals↗
PubMed1998

A stage-specific enhancer of immunoglobulin J chain gene is induced by interleukin-2 in a presecretor B cell stage.

Interleukin-2 (IL-2)-induced transcription of the J chain gene was used as a model for analyzing cytokine regulation during B cell development. To determine whether IL-2 signals are targeted to a J chain gene enhancer as well as to its promoter, the sequences flanking the J chain gene were first examined for DNase I hypersensitivity. Of six sites identified, two strong ones, 7.5 kb upstream of the J chain gene, were found to be associated with an enhancer that is active only during the antigen-driven stages of B cell development. Further analyses of the enhancer in the IL-2-responsive presecretor BCL1 cells showed that the enhancer is activated at this stage by an IL-2 signal that functions by opening the enhancer chromatin and stimulating STAT5 to bind to a STAT5 element critical for the enhancer induction. Moreover, after this early induction stage, the enhancer was shown to be constitutively open and active in terminally differentiated plasma cells.

Base Sequence↗
PubMed1998

Using the Unger system to classify 386 long bone fractures in dogs.

A system already described by Unger and others was used to classify long bone fractures in dogs. The present paper reports experiences using the fracture classification system regarding its ease of use and the ability to analyse the data generated. Three hundred and eighty-six canine long bone fractures were classified from radiographs. Results were assessed by reviewing the medical records or by sending questionnaires to referring veterinarians. There were a few inconsistencies, particularly in classifying proximal ulnar fractures, but the system was easy to use and data retrieval was readily accomplished. Data from the system were used to compare the results of repairs of diaphyseal fractures of the radius/ulna, femur and tibia/fibula. A chi square analysis was used to determine significant differences between the outcome scores of the three fracture types. Fractures of the femoral diaphysis had a statistically poorer outcome than did diaphyseal fractures of the radius/ulna or tibia/fibula.

Animals↗
PubMed1998

Effects of single, short-term exposures of human retinal pigment epithelial cells to thiotepa or 5-fluorouracil: implications for the treatment of proliferative vitreoretinopathy.

AIM: To investigate the effects of single, short-term (5 or 30 minutes) exposures to thiotepa or 5-fluorouracil (5-FU) on collagen lattice contraction and retinal pigment epithelial (RPE) cell proliferation. METHODS: For collagen contraction studies, RPE cells seeded into free floating type I collagen lattices were exposed to single 5 or 30 minute treatments with thiotepa (0.06-4 mg/ml), or 5-FU (0.25-25 mg/ml), or phosphate buffered saline alone as a control. For proliferation studies, RPE cell monolayers were similarly exposed to these agents. The degree of contraction, effects on cell number, and viability were determined up to 14 days after treatment. RESULTS: Contraction of collagen lattices containing RPE cells and proliferation of RPE cells were significantly inhibited (p < 0.05) by thiotepa and 5-FU at concentrations above 0.06 mg/ml and 0.25 mg/ml respectively (for both 5 and 30 minute treatments), compared with controls. Cell death did not occur except for exposure of the RPE cells in collagen lattices to the highest concentration of thiotepa (4 mg/ml). CONCLUSION: It was concluded that single 5 or 30 minute exposures to thiotepa or 5-FU significantly inhibited collagen contraction and the proliferation of RPE cells. These findings suggest that short, single, non-toxic exposures to thiotepa or 5-FU which can be reproduced clinically may be useful in the modulation of proliferative vitreoretinopathy.

Alkylating Agents↗
PubMed1996

Non-vascular vitreoretinopathy: the cells and the cellular basis of contraction.

BACKGROUND: We consider epiretinal membrane in terms of the two repair processes of gliosis and fibrosis and look at the cellular basis of contraction. METHODS: Pathological material removed at surgery was examined by a range of morphological procedures. Cultures of fibroblasts, retinal pigment epithelium cells and retinal glia were subjected to bioassays which relate to behavioural activities in scar formation. RESULTS AND CONCLUSIONS: Our findings highlight the importance of activities such as migration and adhesion in the formation of epiretinal membranes, and also show that these activities are central to our understanding of contraction.

Animals↗
PubMed1996

'En bloc' dissection of epimacular membranes using aspiration delamination.

'En bloc' dissection is a technique in which epiretinal membranes (ERM) are separated from the retina as a single lamina with a 20-gauge blunt flute needle. We used this technique to remove epimacular membranes of various aetiologies in a consecutive series of 25 eyes, with a minimum follow-up of 5 months (mean 10.4 months). Small residual epicentres of ERM away from the fovea remained in 7 (29.1%) eyes only; 3 were inside and 4 outside the temporal vascular arcades. Postoperatively 64% (16/25) of patients achieved a final visual acuity of 6/12 or better and 76% (19/25) achieved a final visual acuity of 6/18 or better. Progressive lens opacities were the most important postoperative complication in phakic eyes that significantly affected the visual results. This technique successfully removed epimacular membranes over a wide area, without the need to find a starting edge or the use of sharp instruments near the retina. Diaphanous ERMs with ill-defined borders and tenaciously adherent membranes could be removed with minimal trauma to the underlying retina. Histopathological and immunohistochemical examination of 10 ERMs demonstrated the absence of internal limiting lamina in 6 (60%).

Adolescent↗
PubMed1995

Comparison of two cochlear implant speech processors in better versus poorer performers.

The performance and subjective preferences for two different speech-processing strategies, the Speak strategy in the Cochlear Spectra 22 speech processor and the Multipeak (Mpeak) strategy in the Mini Speech Processor (MSP), are compared within two adult patient groups. Ten experienced cochlear implant (CI) users were selected for this study. One group of 5 CI users have significant open-set speech recognition, and the second group consisted of experienced CI users who have little or no open-set speech recognition on standardized tests (< 30% on sentence tests; < 10% on monosyllabic word tests). While only 4 of the 5 users in each group were available to complete this evaluation, suitable comparisons on the Speak and Mpeak strategies on test performance were possible within each patient group. The performance tests were necessarily different to suit each patient group; however, general trends of test scores and subjective evaluations of each speech processor are compared between these two groups. While the performance scores and subjective ratings consistently favored the Speak strategy in the first group of users, with good open-set speech recognition, the results within the second group were more variable. These findings have significant implications for individual patient and processor selection.

Cochlear Implants↗
PubMed1994

Phase I trial of intravenous and intraperitoneal administration of granulocyte-macrophage colony-stimulating factor.

To assess the toxicity, pharmacokinetics, and local and systemic effects of the intraperitoneal (i.p.) administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) at various dosages, 13 patients with predominantly i.p. malignancies refractory to standard chemotherapy were studied. GM-CSF was administered intravenously (i.v.) for 5 consecutive days; 21 days later the same dosage of GM-CSF was administered i.p. for 5 consecutive days. Four dosage levels were studied: 1, 2, 4, and 8 micrograms/kg/day. GM-CSF was well tolerated after i.v. and i.p. administration at doses up to 8 micrograms/kg/day. A transient fall followed by an elevation of circulating white cells was observed over a 24-h period after both i.v. and i.p. GM-CSF administration (mean minimum +/- SE as % baseline): 38 +/- 8% at 30 min after i.v. administration, 21 +/- 5% at 60 min after i.p. administration; mean maximum: 220 +/- 41% at 6 h after i.v. administration, 202 +/- 39% at 12 h after i.p. administration). The magnitude and time course of these changes were very similar for the two routes despite an up to 400-fold difference in serum GM-CSF levels at the same time points. Changes in leukocyte count and differential and neutrophil function were also similar over the 3-week period after both i.v. and i.p. administration. In the only patient who had i.p. GM-CSF levels assayed, i.p. administration achieved high levels of GM-CSF in peritoneal fluid (Cmax 343 ng/ml) with maintenance of high concentrations over 24 h (C24h 128 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

The development of a test of speech reception disability for use in 5- to 8-year-old children with otitis media with effusion.

The study aims to develop a test of speech reception disability under simulated classroom conditions for use in young (5-8 year old) schoolchildren, to manage children with otitis media with effusion more effectively. A new video test, TADAST (Two Alternative Auditory Disability and Speech Reception Test), has been constructed in stages by extensively modifying the FADAST (Four Alternative) currently used to assess auditory disability in adults. Minimal word pair lists which were easily identifiable in picture form were developed and refined, and then formulated as a two alternative forced choice picture test. The distribution characteristics of the new test were defined in 89 schoolchildren with and without otitis media with effusion (OME) and compared with pure-tone audiometry performed at the same time. The test correlated highly with audiometry in older children. The distribution characteristics revealed a considerable proportion of children with bilateral OME with little functional disability who might otherwise be at risk of surgery. The test appeared to be sensitive to a 'history of OME' effect. Further refinements are needed to develop a final version which could also be used to evaluate hearing disability in 4-year-old children.

Audiometry, Pure-Tone↗