New entities in uveitis.
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HTLV-I Infections↗
Biomedical subjects
S Lightman
Publications and source records attributed to S Lightman.
Many peptides that are present in the external zone of the median eminence are not secreted into the hypophysial portal blood of sheep.
Apart from the well recognized factors that are produced by the hypothalamus and secreted into hypophysial portal blood to regulate pituitary function, there is a range of neuropeptides that are present in the median eminence and could be secreted to serve a modulatory function. In this study we have collected hypophysial portal blood and jugular venous blood from sheep in an attempt to identify which of these putative modulatory peptides might be secreted from the median eminence. We have measured neuropeptide Y (NPY), substance P (SP), galanin (GAL), neurokinin A (NKA), peptide histidine isoleucine (PHI), vasoactive intestinal peptide (VIP), neurotensin (NT) and cholecystokinin (CCK). We also examined the sheep median eminence using immunohistochemistry for NPY, SP and GAL and determined degradation profiles of NPY, SP, GAL and NKA in portal and jugular plasma. In no instance did we find that levels of the above peptides were consistently higher in portal blood than in peripheral blood. In some cases levels of peptide were lower in portal plasma e.g. for NPY (6/10 sheep). In one experimental series SP levels in portal plasma were significantly (p < 0.05) lower than levels in jugular plasma but this was not found in another experimental series. Galanin levels were significantly (p < 0.01) lower in portal plasma compared to levels in jugular plasma. We conducted in vitro studies to determine whether or not the above peptides are selectively degraded in portal blood but were unable to show any differences between the rates of degradation in portal and jugular plasma. Immunohistochemistry revealed projections into the external zone of the median eminence for NPY, GAL and SP. This study shows that none of the above peptides are secreted into the hypophysial portal blood of sheep. For some peptides e.g. GAL, enzymes from the endothelial cells of the portal vessels may enhance degradation. Projections into the external zone of the median eminence of neuronal systems containing these peptides may serve to modulate the secretion of the well recognized release and inhibiting factors by acting on the neurosecretory terminals.
Animals↗
Isolation of retinal lymphocytes in experimental autoimmune uveoretinitis: phenotypic and functional characterization.
Lymphocytes were obtained from the inflamed retinas of Lewis rats with S antigen (S-Ag)-induced experimental autoimmune uveoretinitis (EAU). In early disease 81% of these were CD4+ T cells. Thirty-four per cent of retinal CD4+ T cells expressed the interleukin-2 receptor (IL-2R) and 95% were CD45R-. These phenotypes contrast sharply with those of peripheral blood and lymph node CD4+ T cells isolated from EAU rats and confirm a high level of CD4+ T-cell activation in the retina in early disease. Although the relative proportions of CD8+ T cells increased in late disease, so did those of B cells and CD45R+ CD4+ T cells. We did not find clear evidence of a selective retention of CD8+ T cells in the retinas in late disease. Proliferation assays using retinal preparations demonstrated modest but significant responses to both S-Ag and the purified protein derivative of Mycobacterium tuberculosis (PPD) compared with lymph node preparations. The S-Ag response was abrogated by anti-major histocompatibility complex (MHC) class II monoclonal antibody (mAb). Lymphocyte preparations from inflamed retinas have not been examined previously in vitro but are likely to be useful in defining the precise function of CD4+ T cells during the course of EAU.
Animals↗
Comparison of the effects of frontal and temporal lobe partial seizures on prolactin levels.
The acute effects of partial (focal) epileptic seizures on serum prolactin levels were studied in two groups of patients: (1) 10 with temporal lobe seizures and (2) 11 with seizures that arose from the frontal lobes, recorded on cable video-electroencephalographic telemetry. Six of the eight complex partial seizures of temporal lobe origin were associated with a marked rise in prolactin levels at 10 minutes after onset (rise in levels, from a mean of 279 to 534 mU/L), compared with a rise in only one of the eight frontal lobe complex partial seizures. None of the five simple partial seizures (two of temporal and three of frontal lobe origin) was associated with a marked rise in prolactin levels. This difference in prolactin response following complex partial seizures of frontal and temporal lobe origin may help in the clinical differentiation of these seizures. A failure of prolactin levels to rise does not, however, exclude a diagnosis of complex partial seizures; thus, this measurement will not help in the clinical differentiation of frontal lobe complex partial seizures from psychogenic attacks.
Adolescent↗
Neuropeptide Y immunoreactivity in the spleen and thymus of normal rats and following adjuvant-induced arthritis.
Immunoreactive neuropeptide Y (irNPY) was detected by radioimmunoassay within the rat thymus and spleen. Total spleen and thymus irNPY contents in control animals were 77 +/- 3 ng and 23 +/- 1 ng respectively (means +/- S.E.M., n = 10). Total tissue contents of irNPY 14 days following bilateral adrenalectomy or induction of inflammatory arthritis were not significantly altered compared to controls. Most spleen irNPY coeluted with synthetic NPY after reversed-phase high-performance liquid chromatography, but two peaks of irNPY were detected in thymic extracts. This suggests that NPY may be differentially expressed in tissues of the immune system.
Animals↗
Increased expression and mutation of p53 in choroidal melanoma.
Using CM-1 antibody directed against the human p53 protein, high levels of mutant p53 protein expression were found in 12 out of 18 malignant choroidal melanomas. In contrast, we failed to observe elevated p53 expression, indicating the absence of p53 mutation in seven choroidal naevi, a potentially premalignant condition that can progress to form malignant melanoma. For two choroidal melanomas, we demonstrated that high levels of p53 protein were accompanied by exon 7 mutations. The mutations were found at codon 238, TGT-->TTT and codon 253, ACC-->AGC. These observations suggest that acquisition of abnormalities of the p53 gene may be an important step in the development of malignant melanoma.
Animals↗
Intrauterine infection and the eye.
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Eye Abnormalities↗
Transient vessel wall sheathing in acute retinal vein occlusions.
Three cases are reported which had features similar to, and evolved in a pattern consistent with central retinal vein occlusions and a fourth case is reported which behaved as a hemispheric vein occlusion. However, they differed from classic retinal vein occlusions by having prominent sheathing of the retinal venous vasculature at presentation, which in all four cases resolved within three weeks. There was no evidence for any of these cases having an inflammatory vasculitis. The significance of this transient sheathing is uncertain.
Acute Disease↗
Would taming the T-cell quieten the eye?
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Acquired Immunodeficiency Syndrome↗
Effect of lymphocytic infiltration on the blood-retinal barrier in experimental autoimmune uveoretinitis.
Using an experimental model of autoimmune uveoretinitis, we have examined the relationship of T cell infiltration in the retina to blood-retinal barrier (BRB) breakdown. Sensitive quantitative in vivo techniques were used to examine BRB permeability to sucrose, a low mol. wt non-transported solute. Electron microscopy was also used to localize extravasated horseradish peroxidase, a macromolecular visual tracer, from the retinal vasculature and to identify the route by which any leakage was occurring. No increase in BRB permeability was found prior to lymphocytic infiltration. By day 10 of the disease inflammatory cells could be seen within the structurally intact retina, which was shortly followed by an increase in the permeability of the BRB to sucrose. Only later in the disease process, when damage to the photoreceptor layer became apparent, did extravasation of the macromolecule HRP occur. At no stage of the disease process was there any detectable damage to inter-endothelial tight junctions. The size-dependancy of tracer extravasation in the initial stages of the disease is indicative of a paracellular route being responsible for the increase in BRB permeability. In later stages of the disease some evidence of horseradish peroxidase filled 'vesicle-like' profiles was observed. We suggest that the devastating complication of BRB breakdown in ocular inflammation is a direct consequence of lymphocytic infiltration.
Animals↗
Surgically induced necrotising sclerokeratitis (SINS)--precipitating factors and response to treatment.
The clinical features, treatment, and visual outcome of 52 eyes from 43 patients who developed scleritis following surgery were reviewed. In all patients the scleral inflammation developed adjacent to a surgical wound. Ninety six per cent had necrotising disease and 23% also had evidence of secondary posterior scleritis. Many different types of ocular surgery were implicated and the majority (75%) of the patients had two or more surgical procedures before the onset of the scleritis. Although cataract extraction through a limbal incision resulted in the largest subgroup, scleritis also followed glaucoma, strabismus, and retinal detachment surgery. The latent period between surgery and the appearance of inflammation was short (mean 9 months) except for a small group in whom scleritis occurred many years after squint surgery. Sixty three per cent of patients had evidence of a systemic disease. Early diagnosis and aggressive medical treatment significantly improved the visual outcome. The precipitating factors, pathogenesis, and course of this condition are discussed.
Adult↗
Immunopathology and altered immunity in posterior uveitis in man: a review.
Posterior uveitis is thought to be a T-cell mediated disease since active foci of inflammation, identified in eyes enucleated for the complications of intraocular inflammation, are found to be predominantly composed of CD4+ T-cells. Few B-cells and little immunoglobulin are found suggesting that antibody and immune complex deposition do not play a major role in perpetuating the inflammatory process. As ocular biopsy is not a feasible method for monitoring disease activity and response to treatment, parameters of T-cell activation and retinal damage have been studied in the peripheral blood. These have included antibody and T-cell sensitisation to retinal S-antigen, serum soluble IL-2 receptors and IL-2 receptors on activated T-cells. none of these parameters, however, have been found to be useful in the monitoring of ocular disease activity alone or in the prediction of disease relapse.
Antigen-Antibody Complex↗
Uveitis: management.
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Administration, Topical↗
Use of steroids and immunosuppressive drugs in the management of posterior uveitis.
Posterior uveitis can occur in all age-groups and often has devastating effects on vision. The visual loss can have a variety of causes including cataract formation, vitritis, optic nerve damage and macular oedema. In patients with active inflammatory disease resulting in reduced vision, steroids are still the best drug but cyclosporin is becoming widely used in combination with steroid therapy, in patients who do not respond to steroids alone or in whom the dose of steroids required to control the disease process is unacceptably high. Cyclosporin works specifically on activated T-lymphocytes and does not therefore result in bone marrow suppression like the more conventional immunosuppressive drugs. This paper discusses the indications for treatment in patients with posterior uveitis and how to use steroids, cyclosporin and other immunosuppressive drugs in the management of this condition.
Administration, Oral↗
Vascular changes in the posterior segment in clinical and experimental ocular inflammatory disease.
Posterior segment inflammatory disease can have several different effects on the retinal vasculature, all of which have potentially sight threatening consequences. Blood-retinal barrier breakdown is a common feature of the disease process with resulting retinal and macula oedema. Very little is known about the mechanism of this breakdown and in particular whether it is at the endothelial cell membrane or at the tight junctions between the endothelial cells--a matter of importance if better therapeutic regimes are to be devised in the future. This paper looks at this question in two animal models of posterior uveitis using different techniques.
Animals↗
Effect of a long-acting somatostatin analogue (BIM23014) on proliferative diabetic retinopathy: a pilot study.
A pilot study on the use of a continuous infusion of somatostatin, by subcutaneous pumps in the management of proliferative diabetic retinopathy is reported. Two patients out of eight with proliferative retinopathy demonstrated improvement. One patient demonstrated regression of disc new vessels and the other a reduced area of retinal capillary non-perfusion, both demonstrated by fluorescein angiography. Control patients showed worsening of fluorescein leakage over the observation period of four to six weeks whereas the other six patients given the somatostatin infusion did not demonstrate any deterioration. The mechanism of action of somatostatin in this study is unknown but it is thought to have direct anti-angiogenic properties as well as inhibiting growth hormone secretion.
Adult↗