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Biomedical subjects

S G Elner

Publications and source records attributed to S G Elner.

44 records · Page 3Linked to original sources
PubMed1991

Intercellular adhesion molecule-1 in human corneal endothelium. Modulation and function.

The endothelium lining the posterior corneal surface performs physiologic pump functions essential to corneal clarity and integrity. A hallmark of keratitis, anterior ocular inflammation, and corneal allograft rejection is leukocyte adherence to the corneal endothelium (CE) forming keratitic precipitates. To elucidate mechanisms governing cornea-leukocyte interactions, cultured human CE cells and intact corneas were examined for expression of intercellular adhesion molecule-1 (ICAM-1), which binds the lymphocyte function-associated antigen-1 (LFA-1) on all leukocytes and enhances delayed-type hypersensitivity mediated by class II major histocompatibility complex antigens. Immunohistochemistry on culture CE cells using monoclonal anti-ICAM-1 antibody yield positive staining that increased after exposure to interleukin-1-beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (gamma-IFN). Standard leukocyte adherence assays demonstrated ICAM-1-mediated CE-neutrophil binding, which was specifically blocked by antibody to ICAM-1 or antibodies to LFA-1 on neutrophils. In whole human corneas, gamma-IFN increased CE and stromal keratocyte ICAM-1 immunoreactivity and enhanced CE-neutrophil adherence. As in CE cell cultures, antibody to ICAM-1 effectively blocked neutrophil binding to the CE cells of whole corneas. These results are the first to demonstrate ICAM-1 in ocular tissue. They indicate that CE cells express functional ICAM-1, which may be modulated by inflammatory cytokines, ICAM-1 provides mechanisms for keratitic precipitate formation, regulation of corneal leukocyte trafficking and the generation of immune responses that may be crucial to allograft rejection.

Cell Adhesion Molecules↗
PubMed1991

Human corneal interleukin-8. IL-1 and TNF-induced gene expression and secretion.

Corneal leukocytic infiltration is an important component of numerous ocular diseases, but specific corneal-derived leukocyte chemotaxins have not been identified. In this study, the authors identified interleukin-8 (IL-8), a known neutrophil and lymphocyte chemotaxin, to be an important chemotaxin produced by human corneal tissue. In situ hybridization and immunohistochemistry of corneas exposed to human recombinant (r) interleukin-1-beta (rIL-1 beta) or tumor necrosis factor-alpha (rTNF-alpha) revealed significant increases in corneal endothelial and stromal cell IL-8 mRNA (P less than 0.001) and marked increases in cell-associated immunoreactive IL-8 compared with unstimulated controls. ELISA assays revealed four- to eight-fold increases in corneal IL-8 secretion after 24-hour exposures to either cytokine over that obtained with unstimulated corneas (P = 0.01). In neutrophil chemotactic bioassays, significant increases in functional IL-8 were detected in media conditioned by corneas exposed to rIL-1 beta or rTNF-alpha for 24 hours (P less than 0.001). Preincubation of these corneal media with anti-IL-8 antibody significantly reduced neutrophil chemotaxis by more than 80%. These results suggest that the cornea is an active participant in ocular inflammation and raise the possibility that agents used in experimental corneal pocket models may produce indirect effects by inducing corneal secretion of other factors, such as IL-8.

Chemotaxis, Leukocyte↗
PubMed1991

Monocyte chemotactic protein gene expression by cytokine-treated human retinal pigment epithelial cells.

Inflammation involving the retina and choroid is a common clinical problem, but the mechanisms that elicit and maintain ocular inflammation remain poorly understood. Interposed between the sensory retina and the systemic blood circulation within the choroid is the neural-derived retinal pigment epithelium (RPE), which forms part of the blood-retina barrier. The RPE is actively phagocytic and shares several features with mononuclear phagocytes of bone marrow origin, including the production of a neutrophil chemotactic factor, interleukin 8, after stimulation with interleukin 1 beta (IL-1 beta) or tumor necrosis factor alpha (TNF-alpha). Because monocyte-derived macrophages are present in retinal lesions of many common and blinding diseases, we monitored human RPE cells or monocyte chemotactic protein (MCP) mRNA expression and activity following cytokine stimulation. Cultured human RPE cells were left unstimulated or exposed to recombinant human IL-1 beta, TNF-alpha, or lipopolysaccharide. MCP mRNA expression in RPE cells and biologically active MCP in RPE cell supernatants were present 1 hour after stimulation and maintained for 24 hours. Conditioned media from RPE cells stimulated with 20 ng/ml of IL-1 beta or TNF-alpha for 24 hours contained biologically active monocyte chemotactic activity that rose rapidly from baseline levels over 4 hours and plateaued over the subsequent 20 hours. RPE chemotactic activity was dose dependent using concentrations of these cytokines ranging from 20 pg/ml to 20 ng/ml of 4-hour assays. Time- and concentration-dependent expression of RPE cell MCP mRNA was also found in the same cultures. Peak MCP mRNA expression occurred after 8 hours of stimulation with IL-1 beta or TNF-alpha. Maximal steady-state MCP mRNA expression occurred at 20 ng/ml for IL-1 beta. Immunohistochemical staining using specific anti-MCP antibodies resulted in distinctive RPE cell staining, confirming the presence of MCP in human RPE cells. These findings demonstrate that cytokine-stimulated RPE cells may evoke or augment mononuclear phagocyte-mediated ocular inflammation by synthesizing MCP.

Cells, Cultured↗
PubMed1990

Ocular and associated systemic findings in suspected child abuse. A necropsy study.

We reviewed complete ocular and systemic necropsy findings of 10 consecutive children who died of suspected child abuse. All 10 children had evidence at necropsy of blunt head trauma, although external signs of blunt trauma occasionally were covert. Ocular injuries were observed in 7 of the 10 cases and when present always included retinal, vitreous, and subdural optic nerve hemorrhages. In 5 cases, intrascleral hemorrhage from the circle of Zinn occurred at the sclera-optic nerve junction. In 4 cases, traumatic retinoschisis or tractional retinal folds were present. Anterior segment findings were uniformly consistent with blunt trauma. Hemosiderin, indicating old hemorrhage, was present in 3 cases. Intracranial hemorrhage, present in all cases with abnormal ocular findings, was always accompanied by signs of direct head trauma, such as subgaleal hemorrhage, skull fracture, cerebral contusion, or external contusions, which are sometimes subtle or hidden beneath the hair.

Child Abuse↗
PubMed1990

Neutrophil chemotactic factor (IL-8) gene expression by cytokine-treated retinal pigment epithelial cells.

The neural-derived retinal pigment epithelium (RPE) underlies the sensory retina and is central to both retinal homeostasis and many common retinal diseases. Retinal pigment epithelium cells are actively phagocytic and share several features with macrophages that have recently been shown to produce a neutrophil chemotactic factor (NCF), also known as interleukin-8, after cytokine stimulation. Because RPE cell responses to cytokines are largely unknown, human RPE cell NCF production was monitored after interleukin-1-beta (IL-1 beta), tumor necrosis factor-alpha, or lipopolysaccharide stimulation. RPE NCF mRNA expression and RPE production of biologically active NCF was time and concentration dependent. Maximal NCF mRNA expression occurred at 20 ng/ml for IL-1 beta. Messenger RNA expression in RPE cells and biologically active NCF in RPE cell supernatants were found 1 hour after stimulation and were maintained for 24 hours. These findings demonstrate that cytokine-stimulated RPE cells may evoke or augment neutrophil-mediated inflammation by synthesizing NCF, a cytokine that may be important in ocular disease mechanisms.

Biological Assay↗
PubMed1988

Anterior proliferative vitreoretinopathy. Clinicopathologic, light microscopic, and ultrastructural findings.

Proliferative vitreoretinopathy (PVR) involving the posterior and equatorial retina is an established clinicopathologic entity. Clinically, a similar process, anterior PVR (APVR), results in anterior dragging of the peripheral retina by membranes which connect to the ciliary body or iris and cause circumferentially and radially fixed retinal folds. The pathology of APVR, however, has not been reported. The authors describe pathologic findings in 28 cases of APVR and ultrastructural pathologic findings in 6 surgical APVR specimens. Anterior PVR was frequently associated with retinal detachment (RD) repair (96%) and trauma (38%). Residual vitreous at the vitreous base virtually always provided a scaffold for membranes containing proliferating cells and deposited extracellular matrix. Major components of APVR membranes were fibrovascular tissue (71%), pigment epithelial cells (43%), fibrous and corneal stromal ingrowth (32%), and glial proliferation (18%). Because of its anterior location, APVR membranes also incorporated ciliary epithelium and corneal endothelium. Contraction of APVR membranes caused anterior retinal displacement and detachment in anatomic configurations corresponding to narrow and wide peripheral troughs. The authors' findings indicate that APVR is a distinctive clinicopathologic entity which may complicate rhegmatogenous RD and its repair.

Adult↗
PubMed1987

Lysosomal enzyme activities in cultured trabecular-meshwork cells.

We examined the lysosomal enzyme levels in cultured trabecular meshwork cells. Histochemical studies revealed that bovine trabecular meshwork cells stained prominently for acid lipase, acid phosphatase, and acid esterase activities. Following phagocytic challenges, such as incubations with latex microspheres or zymosan particles, lysosomal enzyme staining was visibly enhanced. The uptake of foreign particles by trabecular-meshwork cells was evident. Data from biochemical assays for acid lipase, cholesteryl esterase, and acid esterase confirmed the histochemical findings. These results indicate that trabecular meshwork cells are actively phagocytic in culture and that lysosomal enzyme levels in these cells may be modulated by phagocytic challenge.

Acid Phosphatase↗