Biomedical subjects

G J Jaffe

Publications and source records attributed to G J Jaffe.

At least 55 records · Page 3Linked to original sources

PubMed1996

Retinopathy and optic neuropathy in bone marrow transplantation for breast cancer.

PURPOSE: To characterize the ocular toxicity of a bone marrow transplant regimen does not include total body or focal head irradiation. METHODS: Nine patients with advanced breast cancer were referred for visual symptoms after high-dose chemotherapy with cisplatin, cyclophosphamide, and carmustine and autologous bone marrow transplantation without total body irradiation or local head irradiation. RESULTS: Symptoms consistent with optic neuropathy and retinopathy developed in five patients. Retinopathy alone developed in three patients and optic neuropathy alone developed in one. Retinal abnormalities included cotton-wool spots, intraretinal hemorrhages, and macular exudate. Optic nerve findings included disk swelling and subsequent pallor. Symptoms and signs associated with retinopathy were generally reversible, whereas those associated with optic neuropathy often were permanent. Retinopathy and/or optic neuropathy developed in all of the patients from 1 to 5 months after bone marrow transplantation. Resolution or stabilization of findings was observed 2-4 months after presentation. Two patients with optic neuropathy showed progression of field and acuity loss after 4 months. When compared with control subjects, the exposure of patients to cyclophosphamide and carmustine was no different. However, cisplatin exposure was 1.2-fold higher in patients with ocular toxicity compared with control subjects. CONCLUSION: Optic neuropathy and retinopathy are presumed to arise from the administration of a high-dose chemotherapy regimen. As techniques in supportive care improve, long-term adverse effects of these therapies now are becoming apparent.

Adult↗

PubMed1996

Cytomegalovirus retinitis associated with Hodgkin's disease.

BACKGROUND: Patients with intraocular involvement by Hodgkin's disease may present with a variety of ocular abnormalities. Intraocular infections also have been reported in these patients, including two cases of cytomegalovirus retinitis (CMV) diagnosed on postmortem examination. It often is difficult to differentiate between these conditions on clinical examination. METHODS: A patient with Hodgkin's disease presented with an atypical retinitis, vasculitis, and a serous macular detachment. Results of clinical examination, fluorescein angiography, and vitreous biopsy for culture and polymerase chain reaction (PCR) testing are described. RESULTS: The diagnosis of an atypical CMV retinitis simulating possible intraocular involvement by Hodgkin's disease was confirmed by PCR testing of undiluted vitreous. Intravenous therapy with foscarnet, guided by the results of the vitreous biopsy, resulted in resolution of the retinitis and an improvement in vision. CONCLUSION: Intraocular involvement by cytomegalovirus retinitis can simulate intraocular lymphoma in a patient with Hodgkin's disease Polymerase chain reaction testing was useful in establishing the diagnosis and guiding successful therapy in this patient.

Adult↗

PubMed1996

An intravitreal device providing sustained release of cyclosporine and dexamethasone.

PURPOSE: A device that releases cyclosporine and dexamethasone into the eye for extended periods of time might be beneficial in diseases such as proliferative vitreoretinopathy and uveitis. In this study we examine the pharmacokinetics and toxicity of cyclosporine and dexamethasone combined in an intravitreal sustained-release device and the toxicity of a similar device containing only dexamethasone in rabbits. METHODS: Rabbits were divided into three groups for (1) evaluation of the drug tissue levels and device release kinetics following implantation of a device containing 100 micrograms of cyclosporine labeled with 2 microCi of 3H-cyclosporine and 2 mg of dexamethasone; (2) evaluation of the toxicity of this intravitreal device; and (3) evaluation of the toxicity of a similar device containing 2 mg of dexamethasone only. Cyclosporine was measured using a scintillation counter and dexamethasone was measured by high pressure liquid chromatography (HPLC). Toxicity was evaluated by electroretinography, clinical examination, and light microscopy. RESULTS: Vitreous concentrations of cyclosporine (+/- standard deviation) averaged 0.06 (+/- 0.02) microgram/ml over 10 weeks. The average dexamethasone concentration over the 10 week period was 2.9 (+/- 0.9) micrograms/ml. Devices containing cyclosporine and dexamethasone released each drug at rates similar to devices containing cyclosporine or dexamethasone alone. Devices containing both cyclosporine and dexamethasone caused reversible depressions in the b-wave amplitude of photopic and scotopic electroretinograms (ERG's). There was no evidence of toxicity associated with the devices containing dexamethasone only. There was no drug-related toxicity evident on clinical or histopathologic examination of eyes with devices containing the combination of cyclosporine and dexamethasone or dexamethasone alone. CONCLUSIONS: We conclude that the device maintains potentially therapeutic levels of both cyclosporine and dexamethasone in the vitreous. Reversible electroretinographic abnormalities are attributable to cyclosporine. A sustained-release device containing cyclosporine and dexamethasone may be useful for reducing inflammation in diseases such as proliferative vitreoretinopathy and uveitis.

Animals↗

PubMed1996

Clearance of antitransferrin receptor immunotoxin from the rabbit eye.

PURPOSE: Antitransferrin receptor immunotoxin has potent antiproliferative effects on proliferating human ocular cells in vitro, and shows promise in the treatment of ocular proliferative diseases, such as proliferative vitreoretinopathy, bleb scarring after trabeculectomy, or corneal epithelial downgrowth syndrome. Before treating patients, the pharmacokinetics of immunotoxin must be known. The purpose of this study was to determine the clearance of antitransferrin receptor immunotoxin from the rabbit eye after ocular injection. METHODS: Immunotoxin (1,000 ng/0.1 ml PBS) was injected into the vitreous cavity of gas vitrectomized rabbit eyes. Immunotoxin in aqueous, vitreous, and plasma was measured by ELISA at various times after injection. Similar measurements were obtained after immunotoxin was injected into the anterior chamber or subconjunctival space of eyes which had not received vitrectomy. Cultured human retinal pigment epithelial cells were exposed to vitreous fluid obtained after intravitreal injection, and counted after four days, to determine the bioactivity of immunotoxin recovered from vitreous samples. RESULTS: Immunotoxin was cleared rapidly from the vitreous cavity over the first 24 hr (t1/2 = 8.0 hr), and thereafter was slow. Drug recovered from the vitreous cavity retained significant antiproliferative activity at 96 hr. Immunotoxin was cleared within 6 hr from the aqueous after anterior chamber injection, and was not present inside the eye after subconjunctival injection. The plasma did not contain immunotoxin after any of these injections. CONCLUSIONS: The favorable pharmacokinetics of antitransferrin receptor immunotoxin in the rabbit eye suggests that it could be useful in the treatment of ocular proliferative disorders.

Animals↗

PubMed1996

Ocular toxicity following high dose chemotherapy and autologous transplant.

A 49-year-old woman received an autologous transplant for breast cancer. Six weeks later she noticed visual disturbance of the left eye which correlated with a visual field abnormality. There was a milder degree of visual disturbance in the right eye. Treatment with high-dose steroids partially stabilized the problem, which was felt to be an ischemic optic neuropathy. She ultimately died of respiratory failure. Pathology of the optic nerves revealed demyelination. Visual disturbances following high-dose chemotherapy are uncommon; the pathology to date has not been elucidated. Steroid therapy may be useful.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1996

Intravitreal sustained release corticosteroid-5-fluoruracil conjugate in the treatment of experimental proliferative vitreoretinopathy.

PURPOSE: Proliferative vitreoretinopathy (PVR) remains the most common cause of failed retinal detachment (RD) surgery. The authors compared the effectiveness of two intraocular sustained-release codrugs in suppressing PVR in a rabbit model a surgically implantable pellet releasing 5-fluorouracil (FU) and dexamethasone (DX) for 1 week and an injectable intravitreal sustained-release suspension releasing 5-FU and triamcinolone acetonide for 1 month. METHODS: Sustained-release devices and suspensions were prepared to deliver equimolar quantities of corticosteroid and 5-FU. In group 1, devices were implanted surgically into the vitreous of the right eye of 10 New Zealand White rabbits. Ten control rabbits received surgical implantation of the suture only. In group 2, drug suspension was injected into the vitreous of the right eye of 10 New Zealand White rabbits. Ten control rabbits received injection of the vehicle only. One day later, each rabbit was injected intravitreally with 250,000 homologous rabbit dermal fibroblasts. Severity of PVR was graded clinically by two masked observers on days 3, 7, 10, 14, 21, and 28. RESULTS: In group 1, clinical severity of PVR was less in the experimental group than in the control group at all time points, this was only statistically significant on day 10 (P = 0.04). Six eyes developed moderate to severe tractional RD or bullous RD in the control group by day 10 compared with none in the experimental group (P = 0.01). In group 2, the median clinical grading of eyes in the experimental group was significantly less than that in the control group at all time points through day 21 (P < or = 0.01). CONCLUSIONS: Both the intravitreal sustained-release dexamethasone-5-FU device and the triamcinolone-5-FU suspension effectively inhibit the progression of PVR in a rabbit model. Simultaneous delivery of 5-FU and corticosteroid may target different components of the wound-healing process in this disease.

Animals↗

PubMed1995

Binding, coupling, and mRNA subtype heterogeneity of alpha 1-adrenergic receptors in cultured human RPE.

In retinal pigment epithelium, apically applied epinephrine changes the conductance of specific ions which subsequently affects the membrane voltage and stimulates transepithelial fluid transport. In this investigation, myo-[3H]inositol radiotracer studies, radioligand binding with [125I]HEAT, and ribonuclease protection assays were performed to examine the coupling of this receptor to phosphoinositide hydrolysis and the specific mRNA subtypes expressed in cultured human retinal pigment epithelial cells. After labeling second to sixth passage cells with 3-muCi myo-[3H]inositol for 24 hr, epinephrine caused a dose- and time-dependent increase in [3H]inositol phosphate products (EC50 of 0.7 microM). This stimulation was antagonized by prazosin but not by propranolol. The effect of epinephrine was potentiated by the presence of the monoamine oxidase inhibitor, pargyline (10 microM). Pertussis toxin (1 microgram per well) attenuated the stimulatory effect of epinephrine. In the radioligand binding assays, [125I]HEAT binding sites varied among different cell lines, with a range of 44 to 200 fmol (mg protein)-1. Using a ribonuclease protection assay, alpha 1D and alpha 1B, but not alpha 1C, adrenergic mRNA subtypes were detected in cultured human cells. Collectively, these results show that the catecholamines act on a potentially heterogeneous population of alpha 1-adrenergic receptors coupled to phospholipase C by a pertussis toxin-sensitive G protein.

Cells, Cultured↗

PubMed1995

Monocyte-induced cytokine expression in cultured human retinal pigment epithelial cells.

Monocytes and retinal pigment epithelial cells are intimately associated in membranes of eyes with proliferative vitreoretinopathy and in certain types of uveitis. The goal of this study was to determine whether monocytes modulate cytokine expression in retinal pigment epithelial cells, and if so, to identify the monocyte products responsible for this effect. Cultured human retinal pigment epithelial cells were exposed to varying concentrations of monocyte-conditioned medium from unstimulated human monocytes for 1-48 hr, or from monocytes prestimulated with lipopolysaccharide. mRNA expression of interleukin-1 beta, interleukin-6, interleukin-8, melanoma growth stimulating activity/gro alpha and gamma, macrophage colony stimulating factor, transforming growth factor-beta 2, basic fibroblast growth factor and activin beta A chain was determined by reverse transcription polymerase chain reaction. Protein secretion of selected cytokines, interleukin-1 beta, interleukin-6, interleukin-8, macrophage colony stimulating factor and transforming growth factor-beta 2 was measured in RPE-conditioned medium by ELISA. Retinal pigment epithelial cells constitutively expressed mRNA for interleukin-6, macrophage colony stimulating factor, transforming growth factor-beta 2, basic fibroblast growth factor and activin beta A chain. Interleukin-1 beta, melanoma growth stimulating activity/gro alpha and gamma and interleukin-8 were not expressed under basal conditions. Stimulated monocyte-conditioned medium markedly induced mRNA of all cytokines except basic fibroblast growth factor and transforming growth factor-beta 2 in a dose- and time-dependent manner. Unstimulated monocyte-conditioned medium was a less potent inducing agent, but still enhanced mRNA expression of interleukin-6, interleukin-8 and melanoma growth stimulating activity/gro alpha. Stimulated monocyte-conditioned medium also induced a time-dependent increase in interleukin-6, Interleukin-8, macrophage colony stimulation factor and transforming growth factor-beta 2, but not interleukin-1 beta protein secretion (p < 0.05 for all time points). Neutralizing antibodies to interleukin-1 beta, or tumour necrosis factor alpha, but not interleukin-1 alpha, significantly reduced cytokine mRNA expression induced by stimulated monocyte-conditioned medium. The combination of all three neutralizing antibodies almost entirely eliminated monocyte-induced mRNA expression and protein production of all cytokines studied. Activated monocytes secrete a heterogeneous mixture of products that together strongly induce expression of multiple cytokines in human retinal pigment epithelial cells. Most if not all of the inducing effect can be accounted for by interleukin-1 beta and tumour necrosis factor alpha. Because cytokines have been implicated in proliferative vitreoretinopathy and uveitis, monocyte-mediated cytokine expression by RPE cells may serve to initiate and perpetuate these diseases.

Antibodies↗

PubMed1995

Condensation on the posterior surface of silicone intraocular lenses during fluid-air exchange.

PURPOSE: Posterior chamber foldable silicone intraocular lenses (IOLs) are becoming increasingly prevalent in patients undergoing a pars plana vitrectomy with fluid-air exchange. The authors report an important limitation of foldable silicone IOLs during fluid-air exchanges in pars plana vitrectomies. METHODS: The charts of 18 pseudophakic patients with foldable silicone IOLs who underwent vitrectomy with fluid-air exchange by the authors were reviewed. RESULTS: There was a statistically significant difference in the occurrence of condensation during fluid-air exchange between the group of patients with a capsulotomy versus those that did not have a capsulotomy (P = 0.003). Condensation limiting the view of the retina occurred during fluid-air exchange in 11 of 11 of the patients with foldable silicone lenses and a capsulotomy. Attempts to remove the condensation with a soft-tipped aspiration cannula resulted in limited view of the retina for 1 to 2 minutes in 6 of 11 patients. Use of a thin film of silicone oil restored the view in one patient. In the presence of an intact posterior capsule, condensation did not occur on identical foldable silicone IOLs in seven of seven patients. CONCLUSION: Recognition of the presence of a foldable silicone lens is important when an air-fluid exchange is anticipated. If a capsulotomy is present, the surgeon must be aware that condensation may limit the view of the retina severely during and after surgery. Intraoperatively, the view of the retina usually can be restored in short surgeries by wiping the posterior lens surface with a soft-tipped cannula, and in more complex surgeries by applying a thin film of silicone oil on the posterior surface of the lens.

Cataract Extraction↗

PubMed1995

Removal of optic disc stalks during diabetic vitrectomy.

BACKGROUND: The morphologic features and clinical consequences of removing residual optic disc stalks during vitrectomy for complications of diabetic retinopathy have not been described. METHODS: Twenty-four residual optic disc stalks that were surgically removed from eyes with proliferative diabetic retinopathy and dense nonclearing vitreous hemorrhage and/or traction retinal detachment were studied histologically using conventional hematoxylin and eosin staining as well as a modified Glees staining technique. RESULTS: Histologic examination demonstrated that 79% of the specimens consisted of vascularized glial tissue with an infiltrate of mononuclear cells and 21% consisted of glial membranes devoid of vasculature. Axons were identified in 33% of all tissues studied. Intra-operative hemorrhage occurred in three eyes with strongly adherent optic disc stalks and was controlled with transient elevation of the intraocular pressure. The presence of axons in the removed optic disc stalks was not correlated with a decreased final postoperative visual acuity (median time to follow-up 21 months). CONCLUSIONS: Residual optic disc stalks removed during vitrectomy for proliferative diabetic retinopathy frequently contained axons. The presence of axons does not portend an unfavorable postoperative visual outcome.

Adult↗

PubMed1995

Vitrectomy for vitreomacular traction syndrome with macular detachment.

PURPOSE: To describe the clinical characteristics of the vitreomacular traction syndrome with macular detachment and to report our surgical experience with this condition. METHODS: A retrospective chart and photographic review was performed on nine patients (nine eyes) who had a symptomatic decrease in visual acuity from a macular traction retinal detachment caused by vitreomacular traction syndrome. Vitrectomy was performed in each eye to reattach the retina. RESULTS: Intraoperative observation confirmed partial posterior vitreous separation with adherence of the posterior hyaloid to the detached retina and separation of the posterior hyaloid from the attached retina. After surgery the macula was reattached in seven eyes (78%). Visual acuity was improved in four eyes, stable in four eyes, and worse in one eye. CONCLUSION: Macular detachment may occur secondary to vitreomacular traction syndrome. Although the retina may be reattached surgically in these cases, visual improvement may be limited by chronic detachment, premacular fibrosis, cystoid macular edema, or macular schisis.

Aged↗

PubMed1995

Cytokines in proliferative diabetic retinopathy and proliferative vitreoretinopathy.

We determined whether interleukin-8, monocyte chemotactic protein-1, and macrophage-colony stimulating factor are present in the vitreous of patients with proliferative diabetic retinopathy (PDR) or proliferative vitreoretinopathy (PVR). The levels of these cytokines were measured by specific enzyme-linked immunoassays in vitreous from 30 patients with PDR, 13 patients with PVR, and 26 control individuals, including 10 cadaver eyes and 16 patients with idiopathic macular holes, idiopathic macular puckers, vitreous hemorrhages, or uncomplicated retinal detachments. Detectable levels of interleukin-8 were found in 90% of vitreous samples of patients with PDR, 85% with PVR, and 58% of control samples. IL-8 was significantly increased in PDR (mean +/- SEM; 25.0 +/- 5.3 ng/ml; p = 0.01), but not in PVR (11.9 +/- 3.9 ng/ml; p = 0.50) compared to control human vitreous (8.5 +/- 2.5 2.5 ng/ml). MCP-1 was detected in 90% of vitreous samples of patients with PDR, 92% with PVR, and 81% of control samples. MCP-1 was significantly increased in PDR (6.2 +/- 0.9 ng/ml, p = 0.001) and PVR (7.7 +/- 2.5 ng/ml, p = 0.001) over the levels in control vitreous (1.2 +/- 0.2 ng/ml). M-CSF was detected in 94% of vitreous samples of patients with PDR, 88% with PVR, and 92% from control vitreous. M-CSF was significantly elevated in PDR (32.3 +/- 8.3 ng/ml, p = 0.03), but not in PVR (23.6 +/- 12.8 ng/ml, p = 0.4) compared to control (10.7 +/- 3.5 ng/ml). Our results suggest that IL-8, MCP-1, and M-CSF participate in the pathogenesis of PDR and PVR.

Chemokine CCL2↗

PubMed1995

Intravitreal sustained-release dexamethasone device in the treatment of experimental uveitis.

PURPOSE: Uveitis often runs a chronic course requiring long-term therapy. Topical treatment results in poor intravitreal penetration, and systemic therapy is associated with significant side effects. The authors investigated whether an intravitreal sustained-release dexamethasone device was effective in the treatment of severe panuveitis in a rabbit model. METHODS: Twenty New Zealand white rabbits were immunized twice subcutaneously with 10 mg of Mycobacterium tuberculosis H37Ra antigen. Twelve days later, sustained-release dexamethasone devices were implanted into the vitreous of the right eye of 10 rabbits. Ten control rabbits received a sham device. One day later, rabbits were challenged with an intravitreal injection of 33 micrograms of antigen. Three animals in each group were sacrificed on post-challenge days 7 and 13 for aqueous white blood cell (WBC) count, protein determination, and histologic examination. To simulate chronic inflammation with exacerbations, the eight remaining eyes were rechallenged with intravitreal antigen on day 15 and were observed for 3 1/2 months. Inflammation was graded clinically by two masked observers. Retinal function was evaluated by electroretinography (ERG). Light microscopy was used to evaluate the eyes histopathologically. The amount of residual drug in the devices was measured on day 13 and at the end of the experiment. RESULTS: By all clinical criteria measured--anterior chamber cells, flare, and vitreous opacity--treated eyes had significantly less inflammation than untreated eyes (P < 0.05). Clinical examination correlated well with objective data. Both protein concentration (P < 0.05) and aqueous WBCs (P < 0.02) were approximately 10-fold higher, and ERGs were significantly depressed (P < 0.05) in untreated eyes compared to treated eyes. Histopathologic examination showed marked inflammation and tissue disorganization in the untreated compared to the treated eyes. After antigen rechallenge, inflammation in experimental eyes was still less than in control eyes. Late complications such as corneal neovascularization, cataract, and hypotony were also less in the treated eyes than in the untreated eyes. At the end of the experiment (99 days after device implantation), approximately 30% of drug remained in the devices. CONCLUSIONS: The intravitreal sustained-release dexamethasone device is highly effective in suppressing inflammation and preventing complications after two episodes of experimental uveitis in a rabbit model for at least 3 1/2 months. This device may be useful in the management of patients with severe chronic posterior uveitis who cannot tolerate systemic or periocular therapy.

Animals↗

PubMed1994

Treatment and pathogenesis of traumatic chorioretinal rupture (sclopetaria).

Eight eyes (seven patients) with traumatic chorioretinal rupture (sclopetaria) from severe ocular trauma were examined. All seven patients were referred with diagnoses of retinal detachment, giant retinal tear, or ruptured globe. Instead, all eyes had large, peripheral, full-thickness breaks of the choroid and retina without retinal detachment. Seven of eight eyes were initially managed by observation only; one eye was treated with a scleral buckling procedure. The retina remained attached in all eyes for at least six months. Late retinal detachment (more than one year after initial injury) occurred in two eyes because of retinal breaks at a site distant from the original chorioretinal rupture. Two eyes later developed vitreous hemorrhage associated with posterior vitreous detachment and one of these eyes required vitrectomy to clear the visual axis. The pathogenesis of sclopetaria appears to be mechanical disruption and retraction of tissue rather than acute tissue dissolution. The risk of acute retinal detachment is low. We recommend nonsurgical management for the initial treatment of these patients, with continued observation for complications that may later occur.

Adolescent↗

PubMed1994

Inhibition of proliferating lens epithelium with antitransferrin receptor immunotoxin.

We investigated the effect of an antitransferrin receptor immunotoxin (454A12-rRA) on proliferating human and baboon lens epithelium in vitro. Human and baboon lens epithelial cells grown in modified TC-199 medium at 35 degrees Celsius in 7% CO2 were seeded in 24 well plates at a density of 17,500 cells/ml to 40,000 cells/ml. The cells were exposed to various concentrations of 454A12-rRA for seven days. The sensitivity of proliferating human lens epithelium to 454A12-rRA was dependent on the dose, with a 60% to 70% reduction in cell counts at immunotoxin concentrations of 100 ng/ml and above. The immunotoxin had no significant effect on baboon lens epithelium in vitro, which suggests that it is specific for human tissue. By preventing the proliferation of human lens epithelial cells, immunotoxin 454A12-rRA may be useful in the management of posterior capsule opacification after planned extracapsular cataract surgery.

Animals↗

PubMed1994

Review: implants.

An implantable sustained release device has been developed to treat chronic disorders of the eye. The device, consisting of a central core of drug encased in layers of permeable and impermeable polymers, can be implanted subconjunctivally or intravitreally. This technique was used to develop a ganciclovir device which, when implanted into the vitreous, maintains therapeutic vitreous levels of drug for 8 months. Initial studies in patients with cytomegalovirus (CMV) retinitis indicate that this treatment may offer better control of the disease and fewer side effects than existing therapies. Cyclosporine A devices were prepared for the treatment of uveitis. Early data suggests that these devices maintain therapeutic levels in the vitreous for approximately 3 years. Work on efficacy and toxicity is continuing. Although clinical applications of these devices are likely to be restricted to diseases requiring chronic drug therapy, they can be used to investigate optimal delivery rates. Subconjunctivally implanted devices releasing 5-FU for 12 days maintained filters in cynomolgus monkeys for 3 months. Similar devices maintained low intraocular pressure in 75% of high risk filter patients.

Animals↗

PubMed1994

Postoperative fibrin formation and visual outcome after pars plana vitrectomy.

PURPOSE: To determine whether postvitrectomy fibrin formation was associated with visual outcome, a prospective study of patients undergoing pars plana vitrectomy was performed. METHODS: In 121 patients undergoing vitrectomy at the Medical College of Wisconsin between July 1986 and April 1989, the association of fibrin formation and other perioperative factors with visual outcome was evaluated by univariate and multivariate regression analysis. Poor visual outcome was defined as visual acuity worse than 5/200. RESULTS: After a median follow-up period of 23 months (range 6 to 51 months), patients with severe fibrin formation experienced a higher rate of poor visual outcome (19 of 26 patients, 73%) than patients with little or no fibrin formation (23 of 95 patients, 24%; P < 0.0001, univariate analysis). After adjusting for a variety of factors with multivariate regression analysis, fibrin formation was not significantly predictive of final visual outcome. CONCLUSIONS: Factors associated with postvitrectomy fibrin formation may affect visual outcome more than fibrin formation itself.

Adolescent↗

PubMed1994

MGSA/GRO transcription is differentially regulated in normal retinal pigment epithelial and melanoma cells.

We have characterized constitutive and cytokine-regulated MGSA/GRO alpha, -beta, and -gamma gene expression in normal retinal pigment epithelial (RPE) cells and a malignant melanoma cell line (Hs294T) to discern the mechanism for MGSA/GRO constitutive expression in melanoma. In RPE cells, constitutive MGSA/GRO alpha, -beta, and -gamma mRNAs are not detected by Northern (RNA) blot analysis although nuclear runoff experiments show that all three genes are transcribed. In Hs294T cells, constitutive MGSA/GRO alpha expression is detectable by Northern blot analysis, and the level of basal MGSA/GRO alpha transcription is 8- to 30-fold higher than in RPE cells. In contrast, in Hs294T cells, basal MGSA/GRO beta and -gamma transcription is only twofold higher than in RPE cells and no beta or gamma mRNA is detected by Northern blot. These data suggest that the constitutive MGSA/GRO alpha mRNA in Hs294T cells is due to increased basal MGSA/GRO alpha gene transcription. The cytokines interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) significantly increase the mRNA levels for all three MGSA/GRO isoforms in Hs294T and RPE cells, and both transcriptional and posttranscriptional mechanisms are operational. Nuclear runoff assays indicate that in RPE cells, a 1-h IL-1 treatment induces a 10- to 20-fold increase in transcription of MGSA/GRO alpha, -beta and -gamma but only a 2-fold increase in Hs294T cells. Similarly, chloramphenicol acetyltransferase (CAT) reporter gene analysis using the MGSA/GRO alpha, -beta, and -gamma promoter regions demonstrates that IL-1 treatment induces an 8- to 14-fold increase in CAT activity in RPE cells but only a 2-fold increase in Hs294T cells. The effect of deletion or mutation of the MGSA/GRO alpha NF-kappa B element, combined with data from gel mobility shift analyses, indicates that the NF-kappa B p50/p65 heterodimer in RPE cells plays an important role in IL-1- and TNF alpha-enhanced gene transcription. In Hs294T cells, gel shift analyses indicate that IL-1 and TNF alpha induce NF-kappa B complex formation; however, transactivation does not occur, suggesting that subtle differences in the NF-kappa B complexes may result in the inability of the cytokines IL-1 and TNF alpha to activate transcription of the MGSA/GRO genes. IL-1 and TNF alpha posttranscriptionally regulate MGSA/GRO mRNA levels in both cell types. In Hs294T cells, IL-1 increases the half-life of MGSA/GRO alpha from 15 min to 6 h (a 24-fold increase in half-life). These data indicate that IL-1 and TNF alpha transcriptionally and posttranscriptionally regulate MGSA/GRO alpha, -beta, and -gamma mRNA levels in RPE cells, while in Hs294T cells, the major effect of IL-1 and TNF alpha is on mRNA stability.

Base Sequence↗