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S Lightman

Publications and source records attributed to S Lightman.

At least 37 records · Page 2Linked to original sources
PubMed1994

Vitreous fluid sampling and viral genome detection for the diagnosis of viral retinitis in patients with AIDS.

Cytomegalovirus (CMV) causes severe necrotizing retinitis in patients with the acquired immune deficiency syndrome (AIDS) and other herpesviruses have been implicated in the acute retinal necrosis syndrome (ARN), seen in both the immunocompetent and the immunosuppressed. At present the diagnosis of viral retinitis relies solely on clinical appearances. In order to assess whether the detection of herpesvirus-specific DNA in cell-free vitreous biopsy samples could be useful in the early diagnosis of viral retinitis, vitreous fluid samples were taken from 100 patients. Fifty patients had AIDS as defined by the Centers for Disease Control, (MMWR 36 (suppl 1S):1S-15S, 1987) and retinal disease. The remainder were not known to be HIV infected and had no clinical evidence of retinal infection. Each sample was tested for the presence of CMV, herpes simplex virus 1 (HSV-1), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), and human herpesvirus 6 (HHV6), by amplification of viral DNA using a sensitive and specific nested polymerase chain reaction (PCR). The presence of detectable CMV or VZV DNA was clearly associated with clinical disease whereas the presence of HSV-1, EBV, and HHV6 sequences were not. Clinical discrimination between CMV- and VZV-associated retinitis was greatly enhanced when the PCR results were taken into consideration.

AIDS-Related Opportunistic Infections↗
PubMed1994

T lymphocyte effector mechanisms in the retina in posterior uveitis.

Loss of vision in posterior uveitis is often the consequence of chronic retinal oedema and immune-mediated damage to the retinal parenchyma. Research in other putative autoimmune diseases such as rheumatoid arthritis, and in animal models of autoimmune disease, has uncovered a number of mechanisms which may contribute to the development of inflammatory disease within the eye. With recent developments in specific anti-cytokine therapy an understanding of these mechanisms, most of which are cytokine-mediated, is essential in order to plan more effective therapeutic strategies. In this paper we review recent research investigating the functional characteristics of the T cells which are recruited into the retina in experimental autoimmune uveoretinitis, including activation status, antigen-specific proliferation in vitro and cytokine mRNA production in the inflamed retina.

Animals↗
PubMed1994

Orbital floor steroid injections in the treatment of uveitis.

Orbital floor steroid injections, like other posterior periocular injections, are advocated as a means of avoiding systemic immunosuppression in the management of uveitis in which there is significant posterior segment inflammation, but there are no published studies on their efficacy. The results of 54 orbital floor steroid injections to 33 eyes with uveitis were analysed. A positive response with an average duration of effect of 9 weeks was obtained after 48% of injections. These results compare favourably with the results of systemic immunosuppression in patients with comparable patterns of uveitis, thus establishing the efficacy of orbital floor steroid injections and their potential value when systemic immunosuppression needs to be avoided.

Adolescent↗
PubMed1994

The immunological features and pathophysiology of ocular cicatricial pemphigoid.

Ocular cicatricial pemphigoid is an uncommon but severe and potentially blinding systemic disease. It shares many pathophysiological features with the other bullous skin diseases such as dermatitis herpetiformis, bullous pemphigoid and pemphigus vulgaris. All of these diseases have circulating antibodies that bind to the basement membrane of mucous membranes. The individual diseases differ by each having a specific component of the basement membrane complex as its antigen. In acute ocular cicatricial pemphigoid, the conjunctiva is infiltrated with neutrophils, macrophages, Langerhans cells and CD8+ and CD4+ T-cells while in the chronic disease the conjunctiva is infiltrated mainly by CD8+ T-cells. There is evidence of activation of these T-cells as CD4+ cells as shown by expression of the interleukin-2 receptor and increased expression of major histocompatibility class II antigens within the tissue. The aetiology of the fibrosis is unknown but increased amounts of several fibrogenic growth factors are demonstrable by immunohistochemistry.

Aged↗
PubMed1994

Uveitis presenting de novo in the elderly.

Seventy-one consecutive patients presenting with their first episode of uveitis at the age of 60 or more years, were studied retrospectively. The majority were found to have idiopathic uveitides on investigation. In those who did have associated systemic disease, the commonest finding was non-insulin-dependent diabetes mellitus or an autoimmune disease. There were no cases of ocular lymphoma in this series. We conclude that, contrary to some previous reports, idiopathic uveitis may occur in the elderly, and that the relative frequencies of acute anterior, chronic anterior, intermediate and posterior uveitides are similar to those seen in young patients.

Age Factors↗
PubMed1994

Corneal endothelial changes in cytomegalovirus retinitis.

Reticular deposits on the corneal endothelium together with fundus changes typical of cytomegalovirus (CMV) retinitis have been noted in patients with acquired immune deficiency syndrome (AIDS). The aim of this study was to characterise this finding using specular microscopy and to assess the potential of this clinical sign as a screening tool which could be performed rapidly at the slit lamp without the need for dilatation of the pupil. Sixty male homosexual patients with a diagnosis of AIDS as defined by the Center for Disease Control (Atlanta, 1987) were examined at their first visit to the ophthalmic clinic. The cornea was examined at the slit lamp prior to fundal examination and the presence or absence of the characteristic endothelial changes noted. CMV retinitis was diagnosed on the basis of the fundal appearance together with confirmation of the diagnosis by analysis of a vitreous sample. As a diagnostic sign of CMV retinitis the endothelial changes had a positive predictive value of 94.7% and a negative predictive value of 75.6%. Although the presence of the endothelial changes always indicates the presence of CMV retinitis it is not a sign which is found in a high enough proportion of patients to allow its reliable use as a screening tool.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Cells perpetuating the inflammatory response in scleritis.

Scleritis can be a destructive disease frequently associated with autoimmune disorders. It is believed that primary vasculitis plays an important role in its pathogenesis, but little is known about the cellular effector mechanisms. The purpose of this study was to analyse the inflammatory cellular infiltrate in scleritis. Six episcleral biopsies and two enucleated eyes were studied. The episcleral biopsies were taken from patients with nodular scleritis. In one patient enucleation was done after perforation in anterior necrotising scleritis and, in the other after misdiagnosis of posterior scleritis as intraocular tumour. Morphological criteria and immunohistochemical methods were used to characterise the inflammatory cellular infiltrate. The inflammatory cells infiltrating the episcleral tissue were mainly T lymphocytes and macrophages. There was a predominance of CD4 positive cells, but only few lymphocytes were activated (expressed IL-2 receptor). The cells infiltrating the scleral fibres in the enucleated eyes consisted in both cases predominantly of T cells. Clusters of B cells were found in perivascular areas. In circumscribed areas neutrophils, macrophages, and plasma cells were part of the scleral infiltrate. Signs of a granulomatous process with activated macrophages (epithelioid and giant cells) were present in necrotising scleritis. Expression of major histocompatibility class II molecules (MHC II) was found on lymphocytes and rarely on macrophages. Signs of primary vasculitis were not found in any of the specimens. The cellular infiltrate in scleritis shows, at least at certain stages, features compatible with a T cell mediated (autoimmune) disorder, which may have major therapeutic implications.

Adult↗
PubMed1994

[Immunohistologic findings in chronic cicatricial conjunctivitis].

BACKGROUND: Chronic progressive conjunctival cicatrization is found in some mucocutaneous disorders (cicatricial pemphigoid, linear IgA disease) and after long-term treatment with certain topical medications (pseudo-pemphigoid). Little is known about the mechanisms of conjunctival shrinkage, and therapy for these conditions remains difficult. OBJECTIVES: To elucidate the immune mechanisms and assess the main factors involved in conjunctival scar tissue formation in patients with chronic progressive conjunctival cicatrization. PATIENTS AND METHOD: We examined 14 bulbar conjunctival biopsy specimens from patients with chronic progressive conjunctival cicatrization (8 with benign mucous membrane pemphigoid confirmed by biopsy, 4 with the ocular features of benign mucous membrane pemphigoid and 2 with pseudopemphigoid) and 10 biopsies from matched healthy individuals: 1.5 mm sections of glycol methacrylate embedded tissue were analysed with the aid of a panel of monoclonal antibodies. MAIN RESULTS: Cell counts in the subepithelial substantia propria showed a marked increase in T-cells over normal controls (up to 30-fold). Among the T-cell subsets, there were more CD8 than CD4-positive cells observed. Only about 5% of the T-cells were activated (IL-2 receptor-positive). Macrophages were--as in normal tissues--the second most predominant cell. The absolute number was 2-3 times as high in diseased conjunctiva as in controls. There was increased expression of MHC II molecules on macrophages, lymphocytes und fibroblasts. The numbers of B-cells and NK were not increased. CONCLUSIONS: The analysis of the cellular infiltrate showed nonspecific immunopathological characteristics. Thus, the cellular infiltrate gives no explanation for the progressive cicatrization. There is evidence that soluble factors, especially fibrogenic cytokines, play an important role.

B-Lymphocytes↗
PubMed1994

The blood-retinal barrier in experimental autoimmune uveoretinitis. Leukocyte interactions and functional damage.

BACKGROUND: In posterior uveitis the blood-retinal barrier (BRB) plays an important role in the pathogenesis of the disease. However, the morphologic correlate of BRB breakdown and the route of leukocyte migration remain poorly defined. EXPERIMENTAL DESIGN: Using an experimental model of autoimmune uveoretinitis in the rat, we have examined the ultrastructural alterations and leukocyte interactions occurring at the BRB. By employing electron-dense tracers, the development of BRB breakdown, and the route of extravasation were investigated. RESULTS: No increase in BRB permeability was found before lymphocytic infiltration. At day 10 postimmunization with retinal-soluble antigen and beyond, inflammatory cells could be seen within the retina that was quickly followed by an extensive increase in the permeability of the retinal vasculature to lanthanum and horseradish peroxidase. Occasionally, horseradish peroxidase reaction product could be seen extending throughout the 'tight junctions' of the retinal endothelia, but not those of the retinal pigment epithelia. Inflammatory cells, particularly mononuclear cells, were seen forming perivascular cuffs and extending posteriorly towards the outer retina. Retinal damage was initially restricted to the outer nuclear and photoreceptor layers that were in close proximity to these vessels. Leukocytes could be seen adhering to the retinal vessels and penetrating the endothelial cell cytoplasm close to tight junctions, but were never seen probing the junctions directly. At the retinal pigment epithelium, however, there was little evidence of migration into the retina during the early stages of the disease, even though the choroid often became packed with inflammatory cells. At later stages, occasional inflammatory cells could be seen between, and apparently within, retinal pigment epithelium cells in areas overlying sites of severe choroidal infiltration. CONCLUSIONS: The prime site of leukocyte infiltration and damage to the BRB in autoimmune uveoretinitis occurred at the level of the vascular endothelia and that diapedesis takes place primarily via an intraendothelial process.

Animals↗
PubMed1993

Cytokines in the conjunctiva of acute and chronic mucous membrane pemphigoid: an immunohistochemical analysis.

The aim of this study was to evaluate the potential role of certain soluble factors in conjunctival scar tissue formation of pemphigoid patients. Epibulbar conjunctival biopsy specimens were taken from patients with acute ulcerative (n = 4), subacute (n = 8) and chronic (n = 8) mucous membrane pemphigoid and from twelve age-matched healthy individuals. The tissues were embedded in glycol methacrylate and analysed by immunohistochemical methods. Interleukin-2 (IL-2), interferon-gamma, transforming growth factor-beta (TGF-beta), platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), tumour necrosis factor-alpha and proliferating cells (as identified with the antibody Ki-67) were found in both pemphigoid patients and normal controls. Interleukin-4 was not found with this method in either normal or diseased conjunctiva. Significant differences between normal and diseased conjunctiva were found for TGF-beta and for proliferating cells, which were both increased in the acute disease group. More intense staining was found in the subacute disease group for IL-2, bFGF and PDGF. Our findings showed that a variety of cytokines were present in normal and diseased bulbar conjunctiva. Acute conjunctival disease in mucous membrane pemphigoid may indicate active scar tissue formation, implied by an increase in TGF-beta and the presence of proliferating fibroblasts.

Acute Disease↗
PubMed1993

The conjunctiva in acute and chronic mucous membrane pemphigoid. An immunohistochemical analysis.

BACKGROUND: The mechanism of chronic progressive conjunctival cicatrization in mucous membrane pemphigoid is not well understood, and current therapy is often of limited use. Rapid progression of cicatrization follows exacerbations of clinical inflammation, and the investigation of immune mechanisms related to disease activity may provide a clue for more effective therapeutic strategies. METHODS: The authors undertook an immunohistochemical study, using monoclonal and polyclonal antibodies in glycol methacrylate-embedded tissues, of epibulbar conjunctival biopsy specimens obtained from 20 patients with ocular cicatricial pemphigoid and from 12 matched healthy controls. The study patients were classified according to the ocular disease activity as acute ulcerative (n = 4), subacute (n = 8), and chronic (n = 8). RESULTS: The composition of the subepithelial cellular infiltrate varied with disease activity. Acute disease was characterized by an abundance of macrophages and neutrophils. The number of T lymphocytes was significantly raised in all the disease groups, but were most marked in subacute disease. Of the T-cell subsets, there were more CD8- than CD4-positive cells observed, except in acute disease where there were equal numbers. Only approximately 5% of the T cells in all disease groups were activated as demonstrated by expression of interleukin-2 receptor. There was increased expression of major histocompatibility complex class II (MHC II) molecules on macrophages, fibroblasts, and other cells in all the groups. The number of B cells and natural killer cells was not increased. Staining for the fibrogenic cytokines, transforming growth factor-beta (TGF-beta), platelet-derived growth factor, and basic fibroblast growth factor was found in both pemphigoid patients and control persons, but the intensity of TGF-beta staining was significantly greater in acute disease. CONCLUSIONS: The composition of the cellular infiltrate in the bulbar conjunctiva depends on clinical disease activity. The numbers of neutrophils and macrophages seem to reflect clinical disease activity. Fibrogenic cytokines, especially TGF-beta, may play an important role in the formation of conjunctival scar tissue.

Acute Disease↗
PubMed1993

Multiagent chemotherapy in the salvage cure of ocular lymphoma relapsing after radiotherapy.

The eye has traditionally been regarded as a sanctuary site for drugs, but recent publications have shown evidence of penetration by drugs and subsequent clinical response of intraocular lymphomas. In this report, a chemotherapy regimen, including high dose methotrexate and cytosine arabinoside, was used to re-induce remission in a patient with intraocular lymphoma relapsing locally after prior radiotherapy. She remains disease free 18 months later.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Does aldose reductase have a role in the development of the ocular complications of diabetes?

Diabetes mellitus has an effect on many organ systems including the eye, kidney and peripheral nerve. Many of these complications develop in animal models of diabetes, which has allowed some of the mechanisms of damage in target organs to be studied. Aldose reductase, an intracellular enzyme, converts glucose to sorbitol, and it is the intracellular accumulation of sorbitol which is thought to result in irreversible damage. In the diabetic eye the increased sorbitol accumulation in both the lens and the retina has been implicated in the pathogenesis of cataract and retinopathy, the major ocular complications of diabetes. In those experimental models which demonstrate characteristic diabetic complications, pharmacological inhibition of the enzyme aldose reductase has resulted in prevention of target organ damage. This paper summarises the experimental evidence upon which the clinical trials of aldose reductase inhibitors in diabetic patients have been initiated and the results of published drug trials in these patients.

Aldehyde Reductase↗
PubMed1993

Characterization of cellular infiltration in choroidal melanoma.

An immunohistochemical double staining technique was used to examine the characteristics of cellular infiltration in choroidal melanoma. Seven of 16 melanomas examined demonstrated high levels of cellular infiltration, mainly with T-cells and macrophages, and little infiltration with B-cells and NK cells. The majority of T-cells were of the CD8+ type and were activated, as shown by the expression of histocompatibility antigens, HLA-DR and IL2-R. Most of the infiltrating macrophages also expressed HLA-DR antigen. We also detected malignant melanocytes expressing the HLA-DR antigen. This technique could be used to study in detail cellular infiltration in a large number of archival choroidal melanomas with known clinical history, which would enable detection of markers that correlate with the prognosis of the disease.

B-Lymphocyte Subsets↗
PubMed1993

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↗