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Biomedical subjects

M S Loughnan

Publications and source records attributed to M S Loughnan.

17 recordsLinked to original sources
PubMed2002

Phototherapeutic keratectomy re-treatment for recurrent corneal erosion syndrome.

AIMS: Phototherapeutic keratectomy with an excimer laser is commonly used to treat recurrent corneal erosion syndrome. The aim of this study was to determine the success of a repeat phototherapeutic keratectomy for patients with persistent macroerosions following initial treatment with phototherapeutic keratectomy. METHODS: Eight patients who failed primary phototherapeutic keratectomy for recurrent corneal erosion syndrome were treated with repeat phototherapeutic keratectomy. All patients were treated with a superficial therapeutic ablation profile with a Visx, Nidek, or Summit 193 nm excimer laser. All patients were treated for both their primary treatment and re-treatment by the same surgeon. Retrospective analysis of case records of all patients requiring re-treatment was supplemented with a telephone interview. RESULTS: Over a 5 year period (October 1995 to October 2000) 76 eyes were treated for recurrent erosion syndrome with phototherapeutic keratectomy. All patients had documented macroerosions and had failed previous treatment with a lubricant at night. Eight eyes (11%) continued to have macroerosions after this initial treatment; all opted for re-treatment with phototherapeutic keratectomy. Following re-treatment none reported symptoms consistent with a macroerosion. Six of eight patients (75%) are now symptom free; 2/8 (25%) have an occasional foreign body sensation relieved by lubricants. Follow up ranged from 9-60 months with a mean of 25.5 months. CONCLUSION: Re-treatment with phototherapeutic keratectomy appears to be successful for patients with macroerosions complicating recurrent corneal erosion syndrome who have failed conservative management with ocular lubricants and a primary phototherapeutic keratectomy.

Adult↗
PubMed2001

A comparison of different depth ablations in the treatment of painful bullous keratopathy with phototherapeutic keratectomy.

AIM: To study the efficacy of phototherapeutic keratectomy (PTK) for pain relief for patients with painful bullous keratopathy and poor visual potential. METHODS: Patients with painful bullous keratopathy and poor visual potential were treated with superficial PTK (8-25 microm), intermediate (50-100 microm) or deep PTK (25% stromal thickness) using the Nidek EC5000 excimer laser after manual epithelial debridement. Follow up ranged from 1 to 24 months (mean 6.5 months). Outcome measures included symptomatic relief and need for further treatment. RESULTS: In the superficial PTK group five of eight (62%) patients improved symptomatically after treatment. The three (38%) who did not improve went on to have penetrating keratoplasty for pain relief. In the intermediate depth group only two of five (40%) patients had symptom alleviation. The three others (60%) required further procedures. 20 of 24 (83%) patients treated with deep PTK had significant or total alleviation of symptoms. Of these, one developed acute anterior uveitis 9 months after PTK and two required botulinum ptosis for persistent corneal epithelial defects, one of whom had three consecutive episodes of microbial keratitis. Three of 24 suffered occasional discomfort and one patient required a penetrating keratoplasty for continued pain. CONCLUSION: PTK can be a useful therapeutic measure in painful bullous keratopathy with poor visual potential. Deep PTK appears to be more successful in pain management than superficial treatment.

Adult↗
PubMed1996

Mechanical methods in refractive corneal surgery.

The past year has seen considerable advances and debate with regard to several new and some established mechanical means of refractive surgery. Lamellar in situ keratomileusis is gaining increased interest, especially for the treatment of moderate and high myopia, although considerable questions still exist with regard to its safety, predictability, and the possibility of loss of lines of best corrected visual acuity. Mini-radial keratotomy may be of benefit in reducing the risk of traumatic rupture of radial keratotomy incisions, and a refinement of the nomograms for astigmatic keratotomy in the treatment of congenital astigmatism has been proposed. Another report on the use of hexagonal keratotomy for the treatment of hyperopia again raised concerns of its predictability. A blind eye study of intrastromal corneal rings has provided some reassurance with regard to its safety but has also raised doubts over its predictability. Meanwhile, several more reports of the use of both anterior and posterior chamber phakic intraocular lenses for the treatment of myopia have been presented.

Cornea↗
PubMed1994

Thalidomide is an inhibitor of angiogenesis.

Thalidomide is a potent teratogen causing dysmelia (stunted limb growth) in humans. We have demonstrated that orally administered thalidomide is an inhibitor of angiogenesis induced by basic fibroblast growth factor in a rabbit cornea micropocket assay. Experiments including the analysis of thalidomide analogs revealed that the antiangiogenic activity correlated with the teratogenicity but not with the sedative or the mild immunosuppressive properties of thalidomide. Electron microscopic examination of the corneal neovascularization of thalidomide-treated rabbits revealed specific ultrastructural changes similar to those seen in the deformed limb bud vasculature of thalidomide-treated embryos. These experiments shed light on the mechanism of thalidomide's teratogenicity and hold promise for the potential use of thalidomide as an orally administered drug for the treatment of many diverse diseases dependent on angiogenesis.

Animals↗
PubMed1993

A new codon 15 rhodopsin gene mutation in autosomal dominant retinitis pigmentosa is associated with sectorial disease.

OBJECTIVE: To ascertain and characterize rhodopsin gene mutations in autosomal dominant retinitis pigmentosa and to correlate these mutations with the clinical phenotypes. METHODS: DNA was extracted from leukocytes, and the rhodopsin gene was amplified and analyzed using molecular-biological methods. Clinical and electrophysiological data were collected from patient charts. RESULTS: We found a disease-causing mutation that was previously undescribed, to our knowledge, for autosomal dominant retinitis pigmentosa within codon 15 of exon 1 of the rhodopsin gene. It was a single base-pair transversion (AAT to AGT) leading to a serine-for-asparagine substitution. This altered a glycosylation site in the intradiscal portion of the rhodopsin molecule. The pedigree examined demonstrated an inferior distribution of retinal pigmentary changes and predominantly superior visual field loss with relative preservation of electroretinographic amplitudes and good vision, which is consistent with sectorial or sectorial-like retinitis pigmentosa. CONCLUSIONS: A codon 15 rhodopsin gene mutation caused retinitis pigmentosa in the pedigree studied. There may be an association between intradiscal rhodopsin gene mutations and sectorial forms of retinitis pigmentosa.

Adult↗
PubMed1992

Treatment of subfoveal choroidal neovascular membranes with systemic interferon-alpha 2a.

Systemic interferon-alpha has recently been reported to be useful in the treatment of choroidal neovascular membranes (CNVM) in age-related macular degeneration. To further investigate its effect we treated eight patients with subfoveal choroidal neovascular membranes of various aetiologies including idiopathic, age-related macular degeneration and myopic chorioretinal degeneration. Only one of the eight patients responded with an angiographically demonstrated decrease in the size of the CNVM; this was in a patient from the idiopathic group. Considerable side-effects were reported with marked lethargy and malaise limiting compliance with some patients. Although this is an initial report with limited patient numbers and follow-up, it does suggest a role for interferon-alpha in patients with idiopathic neovascular membranes where the retina is otherwise normal, but raises some doubt as to its efficacy in the treatment of age-related macular degeneration.

Adult↗
PubMed1991

Neovascularisation: has the angiogenic factor already been found?

Recently many soluble growth factors capable of influencing neovascularisation (angiogenesis) have been isolated and molecularly cloned. As such they are now available in a highly purified and active form. One or several of these already quite well known molecules may be of importance in the control of ocular neovascularisation. This article reviews what is presently known about growth factor control of neovascularisation with particular emphasis on both the eye and those factors that have already been molecularly cloned. In addition several recently reported inhibitors of neovascularisation are discussed. Such research is of particular interest to the ophthalmologist as knowledge gained in this area may allow for the use of both growth factors as well as growth factor inhibitors in the management of several ocular diseases involving neovascularisation.

Angiogenesis Inducing Agents↗
PubMed1990

Detection by immunofluorescence of surface molecules present in low copy numbers. High sensitivity staining and calibration of flow cytometer.

Receptors for lymphokines and growth factors are present on cell surfaces often at concentrations of 100-500 copies per cell. Although conventional immunofluorescence cannot detect such low levels, cell membrane antigens present at these concentrations can be detected using an optimally set up flow cytometer together with a three-layer immunofluorescence technique, consisting of monoclonal antibody reacted with selected batches of biotinylated horse anti-mouse immunoglobulin and phycoerythrin-streptavidin. In this study we purified and radiolabelled a number of monoclonal antibodies, determined the specific radioactivity by self-displacement analysis, and used the radiolabelled antibody in experiments where the number of molecules of antibody bound per cell and the fluorescence intensity were measured on the same sample. This permitted us to determine the sensitivity of the fluorescence procedure in molecules per cell, using several different antibody/target cell combinations. The method was consistently capable of detecting fewer than 100 molecules of antibody bound per cell.

Antibodies, Monoclonal↗
PubMed1990

A regulatory role for the soluble IL-2 receptor via competition with the p75 cell-surface form of the receptor for IL-2.

Murine T and B lymphocytes can be induced to release soluble interleukin 2 receptors (sIL2R). This receptor is believed to be a truncated form of the p55 chain of the cell membrane-associated receptor. It has been speculated that this receptor may play an immunoregulatory role via competition for IL-2 with the high-affinity (p55/75 heterodimer) IL-2 receptor. Of crucial importance to this hypothesis are both the concentration of the receptor and its affinity of binding for interleukin 2. We report the measurement of the affinity of sIL2R derived from stimulated normal murine splenocytes for IL-2. We also report the quantification of an enzyme linked immunosorbent assay (ELISA) for sIL2R via measurement of the sIL2R concentration in normal murine splenocyte conditioned medium using a radioimmunometric assay and Scatchard analysis. This method of sIL2R quantification is preferable to sIL2R purification and subsequent concentration estimation as used by previous investigators as any purification process risks destruction of some epitopes. Using the above conditioned medium as a standard we have tested supernatants from several cell lines and sera from several different mouse strains for sIL2R. As would be expected this method of quantification yielded a markedly different value for serum sIL2R levels in normal mice than that obtained by previous investigators. Our results indicate that it is very unlikely that sIL2R competes with the high-affinity form of the IL-2 receptor for IL-2. However, it is possible that it competes for IL-2 with the medium-affinity p75 form of the IL-2 receptor and as such is important in restricting unwanted non-specific (bystander) activation of p75 expressing cells. Evidence from both our previous work as well as from the literature is presented to support this hypothesis.

Animals↗
PubMed1989

Interleukins 4 and 5 control expression of IL-2 receptor on murine B cells through independent induction of its two chains.

Resting B cells express few, if any, receptors for interleukin-2 (IL-2), whereas activated B cells can express receptors for and respond to IL-2. IL-2 receptors can exist on the cell surface in three different forms; the complete high-affinity receptor, a heterodimer consisting of a chain of relative molecular mass (Mr) 70-75,000 (70-75K) and a chain of Mr 55K; the 70-75K chain alone, with intermediate affinity for IL-2; or the 55K chain alone, with low affinity for IL-2. We have previously reported that IL-5-stimulated B cells are induced to express the 55K chain. We report here evidence for the differential regulation of the expression of the two chains, namely that IL-4 and IL-5 can independently induce expression of the 70-75K and 55K chains respectively on murine B cells. As expected, cells stimulated to express the 55K chain alone are unresponsive to IL-2, whereas cells stimulated to express either the 70-75K chain or the 70-75/55K heterodimer respond to IL-2, at a high and low ligand concentration respectively, with a marked increase in proliferation. This orchestration of receptor expression and factor responsiveness may represent a novel activation pathway for B cells, where the two chains of a compound receptor are shown to be independently regulated.

Animals↗
PubMed1989

Anti-IL-2 receptor monoclonal antibody AMT-13 increases soluble IL-2 receptor levels in vivo.

A rat anti-interleukin-2 receptor (IL-2R) monoclonal antibody (mAb), AMT-13, has been shown to prolong cardiac allograft survival in mice. However, neither the mechanism of its immunosuppressive action, nor its other in vivo effects, have been studied extensively. We investigated the effect of AMT-13 on serum-soluble IL-2R levels by a quantitative ELISA technique. Following administration of multiple doses of AMT-13, sufficient to delay fetal pancreatic graft rejection, a rapid and lasting increase in soluble(s) IL-2R levels of up to 20-fold was observed. Levels returned to normal by Day 9 despite continued AMT-13 administration. A similar though less marked increase was observed following a single injection of AMT-13. Irradiation with 350 rads decreased sIL-2R levels, whilst rat Ig-treated control mice had sIL-2R levels within the normal range. In vivo administration of recombinant IL-2 also increased sIL-2R levels, but the effect was transient and slight. No effect on either the release of sIL-2R or expression of cell surface-associated IL-2 receptors was noted when splenocytes were cultured in the presence of AMT-13. We speculate that the increased concentration of sIL-2R in the serum of AMT-13-treated mice may play a role in the immunosuppressive action of this mAb.

Animals↗
PubMed1988

Soluble interleukin 2 receptors are released from the cell surface of normal murine B lymphocytes stimulated with interleukin 5.

Murine T and B lymphocytes can be induced to release soluble interleukin 2 receptors (IL2Rs). This receptor is believed to be a truncated form of the 55-kDa chain of the cell-membrane-associated receptor. It has been speculated that this receptor may play an important immunoregulatory role by binding to interleukin 2 (IL-2). We report here that interleukin 5 can induce normal murine B cells to release soluble IL2Rs. This extends our finding that interleukin 5 similarly can induce murine B cells to express functional cell-surface-associated IL2Rs. Two possible mechanisms of release of soluble IL2Rs have been suggested. Soluble IL2R could be synthesized as a secretory form of the receptor lacking the transmembrane domain or by cleavage of the extracellular domain of the cell-surface-associated IL2R at the cell surface. To investigate which mechanism was operative, we radioiodinated the cell surface of normal murine splenocytes that had been cultured for 1 day with Con A to stimulate the expression of cell-surface-associated IL2Rs and the release of soluble IL2Rs. Under the conditions used, radiolabeling of internal proteins was not apparent. Labeled cells were then recultured with Con A, conditioned medium was taken from replicate cultures at various times after radioiodination, and the specific radioactivity of released soluble IL2Rs was determined by ELISA and RIA. We demonstrate that the specific radioactivity and the kinetics of change of the specific radioactivity are consistent with the hypothesis that the soluble IL2Rs are derived from the cell-surface-associated IL2Rs rather than being released in a secretory form.

Animals↗
PubMed1988

Immunosuppressive effect of the anti-IL-2-receptor monoclonal antibody, AMT-13, on organ-cultured fetal pancreas allograft survival.

Recently, prolongation of cardiac allograft survival in mice was reported using a rat anti-IL-2R mAb (AMT-13). However, its immunosuppressive action in vivo, alone and in combination with other immunosuppressants, and its effect on other organ transplants has not been extensively studied. We grafted cultured fetal pancreas from CBA (H-2k) donors to Balb/c (H-2d) mice. Recipients were treated with 10 consecutive daily injections each of 20 micrograms AMT-13 only, or with an additional mild immunosuppression of 350 rads irradiation. Control groups received rat immunoglobulin or 350 rads irradiation. Graft survival and the phenotype of infiltrating cells were assessed histologically and immunocytochemically on days 12, 17, and 21, and soluble IL-2R levels were measured in the serum with a quantitative ELISA in all recipients. Two of five grafts in the AMT-13-treated group had islets on day 12 posttransplantation despite lymphocytic infiltration in all grafts, while at this time all grafts of rat Ig treated control mice were completely rejected with only scar tissue and a few lymphocytes remaining. Additional immunosuppression with 350 rads irradiation had a marked additive effect with AMT-13. Soluble IL-2R levels in the serum of untreated recipients were not elevated compared with normal serum levels, but recipients injected with AMT-13 had multifold increased soluble IL-2R levels. The percentage of IL-2R+ cells in the grafts of AMT-13-treated animals was either normal (less than 5%) or increased (20%) in the additionally irradiated mice, providing strong evidence that the immunosuppressive effect of AMT-13 is not due to a depletion of activated IL-2R+ lymphocytes.

Animals↗
PubMed1987

T-cell-replacing factor (interleukin 5) induces expression of interleukin 2 receptors on murine splenic B cells.

Small, resting B lymphocytes express few, if any, interleukin 2 (IL-2) receptors, but activated B cells may express such receptors. This paper examines the requirements for receptor expression. Normal murine splenocyte populations were enriched for B cells and cultured at relatively low density. IL-2 receptor expression was studied by measuring the binding of the anti-IL-2 receptor monoclonal antibody PC61. Lymphoblasts arising through stimulation by Escherichia coli lipopolysaccharide failed to express IL-2 receptors. B cells cultured with conditioned medium from concanavalin A-stimulated EL4 thymoma cells, with or without LPS, displayed IL-2 receptors. This bioactivity of EL4 conditioned medium could not be replaced by any concentration of B-cell-stimulatory factor 1 (IL-4), IL-1, IL-2, or IL-3 tested. However, the recently cloned lymphokine T-cell-replacing factor (IL-5) was a potent inducer of IL-2 receptor expression, as was the probably identical material known as eosinophil differentiation factor. The receptors so induced appeared to be functional, as receptor-expressing (but not control) lymphoblasts, responded to IL-2 by proliferation, indicative of high-affinity-receptor expression.

Animals↗