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Biomedical subjects

L N Walker

Publications and source records attributed to L N Walker.

13 recordsLinked to original sources
PubMed2004

Late relapse of myelodysplasia after allogeneic transplantation concomitant with new presentation of invasive liposarcoma as a secondary neoplasm.

Second malignancies are uncommon events in the survivors of allogeneic transplant procedures, although they are increased compared to normal control populations. Among these malignancies, sarcomas are exceedingly rare. In addition, relapse of primary myelodysplasia rarely occurs after 5 years from the time of allogeneic transplantation. This report describes an unusual presentation of liposarcoma with concomitant relapse of underlying myelodysplasia developing in a patient 9 years after the first of two allogeneic transplantations.

Hematopoietic Stem Cell Transplantation↗
PubMed1992

Developmental study of chondroitin-6-sulphate in normal and dystrophic rat retina.

The RCS rat is a widely studied model of human retinal dystrophies including retinitis pigmentosa. Chondroitin-6-sulphate (C6S) in the interphotoreceptor matrix was localised immunocytochemically in both the normal congenic and dystrophic strains of the RCS rat up to 65 days postnatally. From postnatal days 5 to 15 the distribution of C6S in both strains was similar, being localised in the interstices of developing inner and outer segments and adjacent to the RPE surface. In the normal rats, the distribution of C6S did not change with age. In the RCS rats, however, at postnatal days 20 to 35 staining was observed as a dense band at the junction of inner and outer segments and no staining was observed adjacent to the surface of the RPE. At postnatal day 45 onwards there was a decrease and a complete absence of C6S staining in these rats. This change in the pattern of staining correlated with the morphological observation of the progressive degeneration of photoreceptor cells suggesting that C6S may be important in photoreceptor degeneration in the RCS rat.

Aging↗
PubMed1991

Cytotoxic effects of residual chemicals from polymeric biomaterials for artificial soft intraocular lenses.

Development of improved hydrogels for soft intraocular lenses, based on 2-hydroxyethyl methacrylate monomer, requires the use of various other monomers and polymerization additives which have potential ocular toxicity. Three monomers, 2-hydroxyethyl methacrylate, methyl methacrylate, and 2-ethoxyethyl methacrylate, as well as two common inhibitors, hydroquinone and 4-methoxyphenol, were subjected to in vitro cytotoxicity assays as aqueous solutions at different concentrations. A new polymerization initiator, 2,2'-azo-bis-(2,4-dimethyl valeronitrile), was thermally decomposed in water at different concentrations and the products were also assayed for cytotoxicity. Assays were based on incubation with human choroidal fibroblasts. Cell death was evaluated by trypan blue dye exclusion, DNA synthesis inhibition, and lactate dehydrogenase tests. While methyl methacrylate and 2-ethoxyethyl methacrylate were found nontoxic, the other chemicals displayed high cytotoxicity. However, when extracts of synthesized poly(2-hydroxyethyl methacrylate) specimens, differentially treated after polymerization, were subjected to the same assays it was found that toxicity from residual 2-hydroxyethyl methacrylate monomer was lost during steam sterilization and storage in water because of the removal of the monomer through aqueous washing. The lack of toxicity in these specimens suggests that residual contents of inhibitor and initiator are too low to cause toxic effects on choroidal fibroblasts. It is concluded that hydrogels have low cytotoxic effects in vitro.

Anisoles↗
PubMed1991

A novel dialysing seton: short-term biocompatibility.

A novel dialysing seton made from haemodialysis tubes was implanted into eleven rabbit eyes to establish its biocompatibility. The animals were observed for up to 67 days after implantation. The cannulae were well tolerated clinically. Tissue obtained at seven different time periods was studied by light and electron microscopy and showed only a mild inflammatory reaction of the same grade as or less than that surrounding nylon sutures used to close the scleral trapdoors. The eye containing the seton had consistently lower intraocular pressure compared to the sham-operated fellow eye for up to 24 days. This effect declined over the ensuing five weeks.

Animals↗
PubMed1989

Subretinal new vessel recurrence in age-related macular degeneration.

Laser photocoagulation with argon or krypton is currently used to treat selected patients with age-related macular degeneration and sudden visual loss from subretinal new vessel formation. In 102 consecutive cases, treated over two years, closure of the vessels was achieved without additional major visual loss in 79% when assessed at two months. Early failure occurred in 21% and was due either to selection of cases with central location or failure to close the new vessel. Later failures due to recurrent subretinal new vessel formation or progression of other macular degenerative changes has occurred in a further 28% so far. Although controlled clinical trials show a significant benefit of treatment, the overall impact of these few successes on the population with macular degeneration is small. Further understanding of the mechanism of subretinal new vessel formation is urgently required. Areas under investigation include the response of injured retinal pigment epithelium, choroid and retina and cellular production of facilitatory factors including proteases and fibronectin.

Aging↗
PubMed1986

Production of platelet-derived growth factor-like molecules by cultured arterial smooth muscle cells accompanies proliferation after arterial injury.

The migration and proliferation of smooth muscle cells (SMCs) within the intima of arteries following mechanical injury is thought to be initiated by vessel wall injury and release of growth factors, in particular the platelet-derived growth factor (PDGF). However, the mechanism by which SMC proliferation is regulated after platelet interaction with the vessel wall has ceased is unknown. Here we show that SMCs derived from the intima of injured rat arteries (intimal SMCs) are phenotypically distinct from SMCs from unmanipulated vessels (medial SMCs). Intimal SMCs secrete 5-fold greater amounts of PDGF-like activity into conditioned medium in culture, have fewer receptors for 125I-labeled PDGF, and are not mitogenically stimulated by exogenous purified PDGF. This study demonstrates that two SMC phenotypes can develop in the adult rat artery and suggests that SMC proliferation in vivo may be controlled, in part, by SMCs that produce PDGF-like molecules.

Animals↗
PubMed1986

Morphology and cell kinetics of fatty streak lesion formation in the hypercholesterolemic rabbit.

The rationale for this study was to determine whether in the hypercholesterolemic rabbit any evidence of endothelial injury could be detected prior to or during the early phase of fatty intimal lesion formation. The data presented showed that in the first 12 weeks of feeding a 0.1% cholesterol-rich diet, rabbit aortas were covered with an intact endothelium. Focal areas of increased endothelial cell replication were observed adjacent to the aortic ostia at 12 and 20 weeks. These replicating cells were almost exclusively located at the shoulders of large raised lesions. In a similar fashion, adherent leukocytes were observed adjacent to the aortic ostia, and at later times they were concentrated at the periphery of these intimal lesions. Smooth muscle cell replication, as assessed by autoradiography, was found to be significantly increased only after 20 weeks of feeding the lipid-rich diet. These data suggest that an increased endothelial cell turnover and leukocyte adhesion were the first detectable changes induced by cholesterol feeding and that smooth muscle cell proliferation occurred soon after these events.

Animals↗
PubMed1985

Immunohistochemical studies of C-reactive protein and apolipoprotein B in inflammatory and arterial lesions.

Interactions in vivo between C-reactive protein (CRP) and apolipoprotein B (apo-B)-containing lipoproteins were sought in inflammatory lesions and atherosclerosis. CRP was demonstrated immunohistochemically on the surface of some muscle fibres in locally induced inflammatory lesions in the rabbit, but apoB was not detected in the same distribution. CRP was not detected in catheter-induced aortic endothelial injuries in the rabbit, in arterial lesions containing apoB from cholesterol-fed rabbits, in apoB-containing human fatty streaks or in advanced human atherosclerotic lesions.

Animals↗
PubMed1983

Endothelial healing following defined injury to rabbit aorta. Depth of injury and mode of repair.

A study has been made of the healing of a narrow deep injury to rabbit aortic endothelium which also involves damage to the media of the vessel. The injury was produced using a nylon catheter containing a wire filament; the injury was approximately 150 micron in width and damaged up to 3 elastic lamellae. Immediately after injury platelet aggregates were observed over the injured areas, several hours later large numbers of leukocytes were also seen to adhere. Two days after injury a non-thrombogenic neointimal surface was observed over deeply injured areas; endothelial cells could be identified covering the injured area at 6 days. The healing process following the injury has been directly compared with the healing of rabbit aortic endothelium following a superficial injury of similar width, where endothelial cells are removed without significant damage to the media of the vessel [1]. The results show that (a) following a narrow injury to the aorta which causes damage to the media platelet aggregation and proliferation of smooth muscle cells occurs, (b) despite the disruption of subendothelial components, endothelium rapidly regenerates over the narrow injured area, although not as quickly as for a superficial injury.

Animals↗
PubMed1982

Narrow superficial injury to rabbit aortic endothelium. The healing process as observed by scanning electron microscopy.

A study was made of the healing of aortic endothelium in rabbits following the production of a defined superficial injury. This was induced using a fine nylon filament which removed the endothelial cells without producing significant damage to underlying structures. The morphology of the injury and subsequent repair was observed using light microscopy and scanning and transmission electron microscopy. Two forms of injury were produced (a) a longitudinal injury along the full length of the aorta which was 50-80 microns wide (about 5-8 cell widths), (b) a circumferential injury approximately 80 microns wide (about 2 cell lengths). Thirty minutes after injury the exposed tissue was almost devoid of adherent cells, but after 4 h became covered by a sparse monolayer of platelets. Occasional leukocytes were also present from 7 h after injury. Injury tracks were found to repair very quickly; re-endothelialisation being complete by 48 h and there being no sign of injury by 7 days.

Animals↗
PubMedDate not supplied

Endothelial healing in the rabbit aorta and the effect of risk factors for atherosclerosis. Hypercholesterolemia.

The effect of diet-induced moderate hypercholesterolemia on endothelial healing has been investigated in the rabbit following a narrow superficial injury to aortic endothelium without damage to the media of the vessel. The healing process was compared with that observed in normocholesterolemic animals. The degree of platelet involvement was similar in both normo- and hypercholesterolemic animals. Reendothelialization occurred within 48 hours in both groups of animals, showing that hypercholesterolemia did not delay endothelial healing. It was found that esterase-positive cells, which morphologically resembled monocyte-macrophages, adhered to and penetrated regenerated endothelium only in hypercholesterolemic animals. After reendothelialization in normocholesterolemic animals, there was no increase in the number of cells within the intima of the vessel and no evidence of lipid accumulation. In hypercholesterolemic animals, cells accumulated in the intima in areas of regeneration, and lipid accumulation occurred within both the intima and the media in areas of regeneration.

Animals↗
PubMedDate not supplied

Improved storage methods for epikeratoplasty.

A major variable in calculating the necessary curvatures and dimensions of the refractive lenticules for epikeratoplasty is the degree of swelling of the donor cornea during storage prior to lathing. The purpose of this study was to determine whether it is possible to restore donor corneas to their in vivo thickness using osmotic agents rather than physical means. The osmotic agents chosen were dextran and chondroitin sulfate. Donor porcine corneas stored in McCarey-Kaufman (MK) medium for seven days increased in thickness by almost 50%. Increasing concentrations of dextran and chondroitin sulfate, and increasing concentrations of dextran with 1.35% chondroitin sulfate added, were examined for their ability to reduce this thickness to normal levels. It was found that 15.00% dextran alone, and 10.00% dextran with 1.35% chondroitin sulfate, reduced corneal thickness to that of fresh tissue. Light and electron microscopy showed that the osmotic agents restored stromal ultrastructure to that of fresh tissue. The use of osmotic agents to reduce corneal thickness prior to lathing reduces physical deformation of the donor tissue associated with the use of a corneal press and may enhance the predictability of epikeratoplasty.

Animals↗