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Biomedical subjects

C S Foster

Publications and source records attributed to C S Foster.

At least 307 records · Page 17Linked to original sources

Corneal laser photocoagulation for treatment of neovascularization. Efficacy of 577 nm yellow dye laser.

The authors treated corneal neovascularization in 25 eyes of 23 patients with corneal laser photocoagulation using 577 nm yellow light. Four groups of patients were treated: patients with corneal neovascularization and active graft rejection (group 1); patients with neovascularization before penetrating keratoplasty (PK) (group 2); lipid keratopathy patients with opacification and/or focal edema threatening the visual axis (group 3); and patients with extensive corneal neovascularization, who were not candidates for PK (group 4). Area of neovascularization and clinical outcome were monitored. After corneal laser photocoagulation, there was a statistically significant reduction in the neovascularized area in group 1 from 32% of corneal area to 10%, and in group 3 from 46% to 27%. All five patients in group 1 had resolution of their graft rejection. In group 3, there was a reduction in the area of corneal opacification from 59% of corneal area to 52%. This difference was not statistically significant. Seven of nine patients in group 3 had stabilization or improvement in their vision over a mean of 9.3 months follow-up. There was no significant change in neovascularized area in groups 2 and 4. In group 2, no rejection reactions occurred over a mean of 5.6 months follow-up after PK. In group 4, corneal laser photocoagulation was disappointing.

Corneal Diseases↗

Ocular cicatricial pemphigoid occurring as a sequela of Stevens-Johnson syndrome.

Ocular cicatricial pemphigoid is a chronic scarring inflammation of the ocular mucosae that can lead to blindness. Although cicatricial pemphigoid has been classified clinically, histopathologically, and immunopathologically, no definite initiating factor or precipitating factor has been identified. In this report, we describe five cases of ocular cicatricial pemphigoid that developed following an acute episode of severe ocular inflammatory injury secondary to Stevens-Johnson syndrome. The time lag between the onset of Stevens-Johnson syndrome and cicatricial pemphigoid ranged from a few months to 31 years. All five patients had linear immune deposits characteristic of cicatricial pemphigoid along the basement membrane zone of mucosal biopsy specimens as detected by either direct immunofluorescence microscopy or direct immunoperoxidase staining. In two patients whose serum was tested, a Western blot assay taken of keratinocyte antigens that had undergone electrophoresis reacted with the serum and identified a 120-kd epidermal antigen detected by the IgG class antibodies. All five patients were treated with systemic immunosuppressive therapy for cicatricial pemphigoid, and we obtained objective responses. Severe ocular mucosal injury such as that which occurs in Stevens-Johnson syndrome may be a precipitating factor in the development of ocular cicatricial pemphigoid.

Adult↗

Purification and characterization of GDP-L-Fuc-N-acetyl-beta-D-glucosaminide alpha 1----3fucosyltransferase from human neuroblastoma cells. Unusual substrate specificities of the tumor enzyme.

Fucosyl residues in the alpha 1----3 linkage to N-acetylglucosamine (Fuc alpha 1----3GlcNAc) on oligosaccharides of glycoproteins and glycolipids have been detected in certain human tumors and are developmentally expressed (reviewed in Foster, C. S., and Glick, M. C. (1988) Adv. Neuroblastoma Res. 2, 421-432). In order to understand control mechanisms for the biosynthesis of these fucosylated glycoconjugates, GDP-L-Fuc-N-acetyl-beta-D-glucosaminide alpha 1----3fucosyltransferase was purified from human neuroblastoma cells, CHP 134, utilizing either the immobilized oligosaccharide or disaccharide substrates. The enzyme, extracted from CHP 134 cells, was purified by DEAE- and SP-Sephadex chromatography and then by either immobilized substrate. alpha 1----3Fucosyltransferase was obtained in approximately 10% yield and was purified 45,000-fold from the cell extract. The kinetic properties of the enzyme showed an apparent KGDP-Fuc 43 microM, KGal beta 1----4GlcNAc 0.4 mM, KGal beta 1----4Glc 8.1 mM, and KFuc alpha 1----2Gal beta 1----4Glc 1.0 mM. Polyacrylamide gel electrophoresis of the affinity-purified enzyme showed two proteins which migrated, Mr = 45,000-40,000. The enzyme differed in substrate specificity, pH optimum, response to N-ethylmaleimide and ion requirements from the enzymes purified from human milk or serum. The inability of alpha 1----3fucosyltransferase to transfer to substrates containing NeuAc alpha 2----3 or alpha 2----6Gal is in contrast to the reports for the enzyme in other human tumors. This substrate specificity correlates with the oligosaccharide residues thus far defined on glycoproteins of CHP 134 cells since NeuAc and Fuc alpha 1----3GlcNAc have yet to be detected on the same oligosaccharide antenna. However, the enzyme transfers to Fuc alpha 1----2Gal beta 1----4GlcNAc/Glc with higher activity than the unfucosylated disaccharides, although neither alpha 1----2fucosyltransferase nor Fuc alpha 1----2 residues have been detected in CHP 134 cells. The different substrate specificities of alpha 1----3fucosyltransferase isolated from human tumors and normal sources leads to the suggestion that a family of alpha 1----3fucosyltransferases may exist and that they may be differentially expressed in human tumors.

Chromatography, Affinity↗

Topical fibronectin in an alkali burn model of corneal ulceration in rabbits.

We studied the effect of topical fibronectin on epithelial wound healing and ulceration in alkali-burned rabbit corneas. After the first 56 hours, fibronectin accelerated complete surface reepithelialization to 4.3 +/- 2.3 days. Control alkali-burned corneas treated with phosphate-buffered saline or albumin did not resurface for 6.7 +/- 3.7 days and 6.2 +/- 2.5 days, respectively. When recurrent epithelial defects occurred, the time required for healing was also significantly accelerated by fibronectin treatment. Corneal ulceration developed in 25 of 28 and 15 of 18 saline and albumin-treated control eyes, respectively; only nine of 18 fibronectin-treated eyes ultimately ulcerated. Immunohistologic studies showed that the initially deposited fibronectin-fibrinogen matrix on the surface of burned corneas had disintegrated by 72 to 96 hours after wounding, corresponding clinically to the time of secondary epithelial breakdown. A prominent fibronectin-fibrinogen matrix remained on the surface of fibronectin-treated corneas, presumably aiding surface reepithelialization and decreasing corneal ulceration.

Administration, Topical↗

Necrotizing scleritis after ocular surgery. A clinicopathologic study.

Necrotizing scleritis may appear after trauma to the sclera. The authors studied 10 patients in whom necrotizing scleritis developed after ocular surgery. The interval between surgery and onset of scleritis varied from 2 weeks to 6 months. Nine patients (90%) were found to have an underlying autoimmune vasculitic systemic disease, which was subsequently treated with immunosuppression. One patient was found to have a local infectious process, which was treated with antibiotics. Appropriate studies led to the discovery and subsequent treatment of a systemic disease or an infectious process in 6 of the 10 patients; the other 4 patients had been previously diagnosed. Results of immunohistochemical studies on resected conjunctival and/or sclera suggest local immune complex deposition, increased HLA-DR expression, and increased helper T-cell participation in conjunctiva and/or scleral tissues after trauma in patients with underlying systemic autoimmune vasculitic disease. The results emphasize the need for meticulous diagnostic pursuit of potentially lethal systemic autoimmune vasculitic disease in patients with necrotizing scleritis after intraocular surgery.

Aged↗

Immunopathology of atopic keratoconjunctivitis.

Conjunctival biopsies from 11 patients with atopic keratoconjunctivitis (AKC) and from 13 age-matched healthy individuals undergoing cataract surgery were analyzed by light microscopy and immunohistochemical techniques. Histology of AKC specimens showed goblet cell proliferation, epithelial pseudotubular formation, eosinophil and mast cell invasion of the epithelium, and pronounced mononuclear cell infiltration of the substantia propria, often with frank granuloma formation. Epithelium of AKC conjunctiva showed significantly more T cells (CD3+, CD5+), T-helper cells (CD4+), macrophages (Mac-1+, CD14+), activated T cells, (CD25+), and dendritic cells (CD1+), and a higher helper/suppressor ratio than did control subjects. In the substantia propria, AKC specimens showed dramatically increased inflammatory cell infiltration with significantly more cells staining, in order of frequency, for T-cells (CD3+, CD5+), T-helper cells (CD4+), T-suppressor/cytotoxic cells (CD8+), macrophages (CD14+, Mac-1+) activated T cells (CD25+), B cells (CD22+), and dendritic cells (CD1+, HLA-DR+). Fifty-three percent of T cells in the substantia propria expressed the interleukin-2 receptor protein (CD25+). These findings indicate that the chronic conjunctivitis of AKC is complex, with activated T-cells and macrophages dramatically participating in the process. Successful long-term control of the potentially binding conjunctival inflammation of this disease is likely to require therapeutic strategies directed toward more than just the mast cell component of the process.

Adult↗

Remission and recurrence after withdrawal of therapy for ocular cicatricial pemphigoid.

Ocular cicatricial pemphigoid (OCP) is a chronic, progressive, autoimmune disease that scars mucus membranes and may lead to blindness. The authors studied the long-term effects of OCP in 104 consecutive patients (average follow-up, 4 years) to determine whether complete remission could be achieved after a course of treatment with immunosuppressive drugs. Prolonged periods of remission while not undergoing therapy were maintained in approximately one third of patients with OCP. Follow-up must be continued for life, as relapse occurred in 22% of those who were in remission and not undergoing therapy. Those who relapsed regained disease control readily upon reinstitution of therapy and did not deteriorate to more advanced cicatrization. Sex, age, initial degree of inflammation, and the incidence of extraocular involvement did not have a prognostic significance on outcome. Mechanisms that underlie the differing responses to therapy are not yet known.

Adult↗

Immunopathology of scleritis.

Conjunctival and scleral biopsies from 25 patients with necrotizing scleritis and 5 patients with recurrent nonnecrotizing scleritis were studied by histopathologic, immunofluorescence, and immunoperoxidase techniques. Vasculitis with fibrinoid necrosis and neutrophil invasion of the vessel wall was present in 75% of the scleral and 52% of the conjunctival specimens. Vascular immunodeposits were found in 93% of the scleral and 79% of the conjunctival tissue tested by immunofluorescence techniques. A dramatic increase in the number of inflammatory cells over normal controls was detected in both tissues by immunoperoxidase techniques. In the conjunctival epithelium, there were significantly more T-helpers, macrophages, and B cells. In the conjunctival substantia propria, there were significantly more T cells of all types, macrophages, and B cells. Likewise, scleral specimens showed an increase over controls of T cells of all types and macrophages. HLA-DR expression was dramatically increased in both tissues. Immune-complex-mediated vasculitis plays a pivotal role in the pathogenesis of necrotizing scleritis and recurrent nonnecrotizing scleritis. Induced HLA-DR expression on ocular nonimmune cells and T cell controlled responses also may participate.

Adult↗

The role of cyclic nucleotide mediators in latency and reactivation of HSV-1 infected neuroblastoma cells.

The mechanisms that control herpes simplex virus type 1 latency and reactivation are still poorly understood. We developed an in vitro murine neuroblastoma cell HSV-infected, acyclovir suppressed model to study the influence of different cyclic nucleotide mediators on the latency and reactivation of HSV-1. A positive cDNA 'in situ' hybridisation for HSV genome was used to prove the establishment of a viral-host cell nuclear relationship. An ABC-immunoperoxidase reaction to cell surface HSV mature glycoproteins was also performed to determine the time of viral reactivation with formation of mature virions. Supernates of cultured cells were placed on Vero cells for confirmation of reactivation by classic cytopathic effect. Theophylline (50 micrograms/ml) and dibutyryl-cAMP (0.1, 0.5, 1 mg/ml) produced the most pronounced response, accelerating HSV reactivation time by 150%. Epinephrine (10, 20 micrograms/ml) had an intermediate effect on accelerating viral reactivation; and verapamil (20, 50 micrograms/ml), theophylline and epinephrine at lower doses had a smaller effect. Carbamylcholine (10 micrograms/ml) prolonged the time to viral reactivation by 100%, 36 hours compared to control time of 18 hours. Insulin (0.1, 0.5, 1 mg/ml) also prolonged HSV 'latency' by six hours. Exogenous dibutyryl-cGMP and carbamylcholine at lower concentrations did not have an effect on viral reactivation. These findings suggest that there is a relationship between changes of intracellular concentration of cyclic nucleotides and HSV latency and reactivation.

Animals↗

Systemic chemotherapy for ocular cicatricial pemphigoid.

The records of 105 patients treated with three different chemotherapeutic agents for ocular cicatricial pemphigoid (OCP) were reviewed to compare long-term efficacies, side effects, and tolerance of different regimens. For the entire group, OCP progressed in 6% of eyes in 10% of patients (follow-up 35 months). More than half of the treatment failures occurred in patients intolerant of chemotherapy. Diaminodiphenylsulfone (DAP), as initial agent, failed to control disease in 2% of patients, compared with 8% after cyclophosphamide (CYC) and 9% after azathioprine (AZA) (p less than 0.05). Stratification of results revealed that DAP was the most effective initial agent for modestly active OCP, whereas CYC was the most effective initial choice for highly active cases. In patients treated with a single agent exclusively for 10 months or more, failure to control disease occurred in 4% of DAP, 4% of CYC, and 15% of AZA patients (p less than 0.01). Recommendations for a sequential approach to chemotherapy for OCP are presented.

Adult↗

Tectonic keratoplasty for peripheral ulcerative keratitis.

Peripheral ulcerative keratitis (PUK) is a destructive, inflammatory process that can lead to corneal perforation and visual loss. Successful control of PUK has been reported with conjunctival resection, cyanoacrylate adhesive, and systemic immunosuppression. Cases with impending or actual corneal perforation may require more extensive surgery, including lamellar or penetrating keratoplasty, to maintain the integrity of the globe. We report on 17 eyes of 14 patients with PUK that required tectonic keratoplasty because of progressive ulceration. Surgery with concomitant immunosuppression preserved the eyes in all but two cases, and 8 of 17 eyes maintained or improved preoperative visual acuity. Six eyes had final visual acuities of 20/200 or better. This therapeutic strategy can preserve eyes that might otherwise be lost to progressive inflammation.

Adult↗

Romberg's progressive hemifacial atrophy: an association with scleral melting.

We report the unusual case of a 43-year-old woman who presented with Romberg's progressive facial hemiatrophy and spontaneous scleral perforation in the ipsilateral eye, for which scleral grafting was performed. Histologic and ultrastructural examination of the scleral specimen revealed a noninflammatory lytic process. The location of the scleral loss, exactly on the line of the "en coup de sabre" atrophy, as well as the light microscopy and ultrastructural histopathologic findings suggest that the scleral destruction was a late manifestation of Romberg's disease.

Adult↗

A comparative study of proliferation indices and ploidy in dysplastic naevi and malignant melanomas using flow cytometry.

Cell proliferation indices and DNA content have been determined in 18 intradermal naevi, 40 dysplastic naevi and 16 superficial malignant melanomas (less than 0.76 mm depth of invasion) using flow cytometry. In this study, proliferation indices of intradermal naevi and dysplastic naevi were not significantly different from each other. Abnormalities of DNA ploidy were not identified in the intradermal naevi or dysplastic naevi; whereas three of the malignant melanomas were aneuploid. In addition, cellular proliferation was increased within the group of malignant melanomas, in comparison with the naevi. This study has found no evidence to indicate that sporadic dysplastic naevi were more likely than intradermal naevi to transform to malignant melanoma, when objective criteria were employed. However, dysplastic naevi could be distinguished from some early malignant melanomas by absence of aneuploidy and by low cell proliferation indices.

Adolescent↗

Morphological and immunohistochemical analysis of the human liver in chronic pancreatitis.

Morphological and immunohistological appearances of liver biopsy specimens are described in a personal series of 52 patients undergoing operation for chronic pancreatitis. The findings are compared with those in a series of 10 histologically normal liver biopsy specimens from patients without pancreatitis. Alcohol was the prime aetiological agent in 40 of the 52 patients (77%). No obvious damage to hepatic parenchymal cells or biliary structures was observed but minor morphological changes of alcohol associated liver disease were seen in 42% of specimens. The most consistent finding, present in 48 specimens (92%), was a chronic inflammatory cell infiltration of portal tracts. In all but one case, T lymphocytes predominated, but a few B cells were present. In four biopsy specimens, T cells spilled over into adjacent hepatic parenchyma, but there was no evidence of T cell mediated cytotoxic damage to the parenchymal cells or biliary epithelium. It is suggested that these inflammatory cells are in transit from the pancreas through the liver via the portal circulation and may reflect the underlying pathogenesis of chronic pancreatitis rather than alcoholic liver disease.

Adult↗

[Herpes simplex virus retinitis. Role of the immune system in the animal experiment].

Herpes simplex virus (HSV) can induce severe inflammation in the retina. Von Szily described a model in which anterior chamber injection of HSV results in anterior uveitis with relative protection of the retina, but contralateral retinitis. The role of the immune system in the von Szily mouse model was investigated in our experiments. Earlier experiments demonstrated resistance to contralateral retinitis in some mouse strains. Our results suggest that natural killer (NK) cells do not play an important role in this phenomenon. In the next step the role of NK cells and T cells in the retinitis was investigated. After depletion of NK cells with anti-NK antibody, sensitive BALB/c and resistant CB17 mice did not have a higher incidence of retinitis. CB-17 mice developed more encephalitis after depletion, demonstrating an important role of NK cells against generalization of HSV. The role of T cells was investigated using T-cell-deficient nude mice. These mice had bilateral retinitis in about 95% of cases, demonstrating the role of T cells in protection of the retina in this model. Anti-HSV-1 serum transfer provided protection for the contralateral retina.

Animals↗