PubMed Health⌕ Search

Biomedical subjects

P Sternberg

Publications and source records attributed to P Sternberg.

At least 19 recordsLinked to original sources
PubMed2004

The Gene Ontology (GO) database and informatics resource.

The Gene Ontology (GO) project (http://www. geneontology.org/) provides structured, controlled vocabularies and classifications that cover several domains of molecular and cellular biology and are freely available for community use in the annotation of genes, gene products and sequences. Many model organism databases and genome annotation groups use the GO and contribute their annotation sets to the GO resource. The GO database integrates the vocabularies and contributed annotations and provides full access to this information in several formats. Members of the GO Consortium continually work collectively, involving outside experts as needed, to expand and update the GO vocabularies. The GO Web resource also provides access to extensive documentation about the GO project and links to applications that use GO data for functional analyses.

Animals↗
PubMed2001

WormBase: network access to the genome and biology of Caenorhabditis elegans.

WormBase (http://www.wormbase.org) is a web-based resource for the Caenorhabditis elegans genome and its biology. It builds upon the existing ACeDB database of the C.elegans genome by providing data curation services, a significantly expanded range of subject areas and a user-friendly front end.

Alternative Splicing↗
PubMed2001

Retinopathy associated with high-dose interferon alfa-2b therapy.

PURPOSE: To present seven patients who developed retinopathy while receiving high-dose interferon alfa-2b therapy for adjuvant treatment of high-risk melanoma. METHODS: Retrospective case series. RESULTS: Seven patients developed a retinopathy while receiving high-dose interferon alfa-2b therapy for adjuvant treatment of high-risk melanoma. Five patients had normal visual acuity, but retinopathy with cotton- wool spots and/or retinal hemorrhages with the retinopathy resolved after stopping treatment after detection. Two patients developed severe retinopathy with vision loss to counting fingers and hand motions without resolution of the retinopathy. The duration of the maintenance treatment before detection of the retinopathy for all patients ranged from 6 to 26 weeks. The total dose received at time of detection of retinopathy ranged from 816 to 1770 million units. Confounding factors included hypertension, thrombocytopenia, anemia, and a history of prior chemotherapy in one patient. Also, one patient received an investigational ganglioside vaccine, one had a history of radiation treatment to the brain, and six received paroxetine. CONCLUSIONS: Patients receiving interferon alfa-2b are at risk for developing an associated retinopathy. The risk appears to be greater with higher dosage therapy. In addition, severe vision loss can be seen with interferon alfa-2b-associated retinopathy. The effect of treatment with selective serotonin reuptake inhibitors, such as paroxetine, in increasing the incidence of this complication is unknown. Patients need to be monitored until the retinopathy is resolved to screen for sequelae, including retinal neovascularization.

Dose-Response Relationship, Drug↗
PubMed2001

Indocyanine green effect on cultured human retinal pigment epithelial cells: implication for macular hole surgery.

PURPOSE: To evaluate potential toxic effects of indocyanine green dye on cultured human retinal pigment epithelial cells. METHODS: Controlled laboratory experiment. Cultured human retinal pigment epithelial cells were exposed to balanced saline solution, balanced saline solution with endoillumination, indocyanine green or indocyanine green with endoillumination. Cells were evaluated by light microscopy, electron microscopy, and a mitochondrial dehydrogenase assay. RESULTS: Retinal pigment epithelial cells exposed to indocyanine green showed no histologic or ultrastructural changes. Those exposed to indocyanine green alone or indocyanine green plus light demonstrated a significant decrease in mitochondrial enzyme activity (P = 0.0002 and 0.005, respectively). CONCLUSION: Brief exposure of cultured human retinal pigment epithelial cells to indocyanine green results in decreased mitochondrial enzyme activity but does not appear to influence cellular morphology or ultrastructure.

Cells, Cultured↗
PubMed2000

Redox state of glutathione in human plasma.

Thiol and disulfide forms of glutathione (GSH) and cysteine (Cys) were measured in plasma from 24 healthy individuals aged 25-35 and redox potential values (E(h)) for thiol/disulfide couples were calculated using the Nernst equation. Although the concentration of GSH (2.8 +/- 0.9 microM) was much greater than that of GSSG (0.14 +/- 0.04 microM), the redox potential of the GSSG/2GSH pool (-137 +/- 9 mV) was considerably more oxidized than values for tissues and cultured cells (-185 to -258 mV). This indicates that a rapid oxidation of GSH occurs upon release into plasma. The difference in values between individuals was remarkably small, suggesting that the rates of reduction and oxidation in the plasma are closely balanced to maintain this redox potential. The redox potential for the Cys and cystine (CySS) pool (-80 +/- 9 mV) was 57 mV more oxidized, showing that the GSSG/2GSH and the CySS/2Cys pools are not in redox equilibrium in the plasma. Potentials for thiol/disulfide couples involving CysGly were intermediate between the values for these couples. Regression analyses showed that the redox potentials for the different thiol/disulfide couples within individuals were correlated, with the E(h) for CySS-mono-Gly/(Cys. CysGly) providing the best correlation with other low molecular weight pools as well as protein disulfides of GSH, CysGly and Cys. These results suggest that E(h) values for GSSG/2GSH and CySS-mono-Gly/(Cys. CysGly) may provide useful means to quantitatively express the oxidant/antioxidant balance in clinical and epidemiologic studies.

Adult↗
PubMed2000

Submacular surgery trials randomized pilot trial of laser photocoagulation versus surgery for recurrent choroidal neovascularization secondary to age-related macular degeneration: I. Ophthalmic outcomes submacular surgery trials pilot study report number 1.

PURPOSE: To report complications and changes in vision during 2 years of follow-up of patients with age-related macular degeneration assigned randomly to surgical removal or to laser photocoagulation of subfoveal recurrent neovascular lesions in a pilot trial designed to test methods, to refine estimates of outcome rates, and to project patient accrual rates for a larger multicenter randomized trial to evaluate submacular surgery. PATIENTS AND METHODS: Eligible patients with previous laser photocoagulation of extrafoveal or juxtafoveal choroidal neovascularization secondary to age-related macular degeneration were enrolled at 15 collaborating clinical centers. Assignments to treatment arm were made by personnel at a central coordinating center. Adherence to eligibility criteria and treatment assignment was assessed centrally at a photograph reading center. Patients were examined at 3, 6, 12, and 24 months after treatment for data collection purposes. Outcome measures reported include treatment complications, adverse events, requirements for additional treatment, and 2-year changes in visual acuity from baseline. RESULTS: Of 70 patients enrolled, 36 were assigned to laser photocoagulation and 34 to submacular surgery; all were treated as assigned. One patient in each group died before the 2-year examination. Visual acuity was measured at the 2-year examination for 31 of the surviving patients (89%) in the laser arm and for 28 of the surviving patients (85%) in the surgery arm. The 2-year measurements for 36 of the 59 patients (61%) were made by an examiner masked to treatment assignment and to the identity of the study eye. Improvements and losses of visual acuity were observed in both treatment arms; 20 of 31 study eyes (65%) in the laser arm and 14 of 28 study eyes (50%) in the surgery arm had visual acuity 2 years after enrollment that was better than or no more than 1 line worse than the baseline level. Changes in visual acuity and the size of the central macular lesions from baseline to the 2-year examination were similar in the treatment arms. Few serious complications were observed in either arm at the time of initial treatment; serious adverse events were rare. During follow-up, 11 laser-treated eyes and 18 surgically treated eyes had additional intraocular procedures. CONCLUSIONS: The data from this pilot trial suggest no reason to prefer submacular surgery over laser photocoagulation for treatment of patients with age-related macular degeneration who have lesions similar to those studied in this pilot trial. Any clinical trial designed to compare submacular surgery with laser photocoagulation in eyes with age-related macular degeneration and subfoveal recurrent neovascular lesions must enroll several hundred patients in order to reach a statistically valid conclusion regarding differences between these two methods of treatment with respect to either changes in visual acuity or complication rates.

Aged↗
PubMed2000

Oxidative damage and protection of the RPE.

This review provides a model for the role of oxidative stress in the etiology of age-related macular degeneration (AMD). Epidemiological studies of diet, environmental and behavioral risk factors suggest that oxidative stress is a contributing factor of AMD. Pathological studies indicate that damage to the retinal pigment epithelium (RPE) is an early event in AMD. In vitro studies show that oxidant treated RPE cells undergo apoptosis, a possible mechanism by which RPE cells are lost during early phase of AMD. The main target of oxidative injury seems to be mitochondria, an organelle known to accumulate genomic damages in other postmitotic tissues during aging. The thiol antioxidant GSH and its amino acid precursors protect RPE cells from oxidant-induced apoptosis. Similar protection occurs with dietary enzyme inducers which increase GSH synthesis. These results indicate that therapeutic or nutritional intervention to enhance the GSH antioxidant capacity of RPE may provide an effective way to prevent or treat AMD.

Aging↗
PubMed2000

Vitrectomy update for macular traction in ocular toxocariasis.

PURPOSE: To study the results of modern vitrectomy in traction and combined traction-rhegmatogenous retinal detachment involving the macula in cases of ocular toxocariasis. METHODS: This was a cohort study of patients seen in different institutions in the United States. Ten eyes of 10 patients were studied. Vitrectomy was performed in all eyes, combined with membrane removal, scleral buckle, fluid-gas exchange, silicone oil, or lensectomy in certain cases. The anatomic and visual results of surgery were reviewed. RESULTS: Ten eyes from 10 patients ranging in age from 2 to 33 years (median, 6 years) were reviewed. Follow-up ranged from 3 months to 8 years (median, 2 years). All eyes achieved macular attachment following surgery; vision improved in 5 (50%) eyes, and was unchanged in 5 (50%). Histologic specimens from six eyes were reviewed, and revealed combinations of fibrous tissue, eosinophils, plasma cells, lymphocytes, and giant cells. One specimen revealed an encysted Toxocara canis organism. CONCLUSION: Inflammation created in response to Toxocara larvae may lead to traction retinal detachment of the macula. Vitreoretinal surgery has a good chance of reattaching the macula and improving vision.

Adolescent↗
PubMed2000

Soccer ball-related retinal injuries: a report of 13 cases.

PURPOSE: To describe the clinical characteristics and management of retinal injuries caused by soccer ball impact as well as the mechanism of injury, prognostic features, risk factors, and possible prevention strategies. METHODS: Thirteen cases of soccer ball injuries from retina referral practices were retrospectively reviewed, with attention to the mechanism of associated ocular complications and the anatomic and visual outcomes. RESULTS: Soccer ball injuries occurred in both male and female patients (9 male, 4 female) with ages ranging from 8 to 21 years (median 14 years). These patients were observed from 0 to 64 months (median follow-up, 8 months). Four patients had traumatic macular holes, two eyes had retinal detachment associated with retinal dialysis, two had retinal tears associated with hemorrhage, one had a choroidal rupture, and one had only vitreous hemorrhage and Berlin's edema. Although six eyes had some degree of traumatic retinal pigment epitheliopathy, it was the primary diagnosis in only three. Visual acuity at presentation ranged from 20/20 to count fingers, with 7/13 (54%) having 20/200 or worse vision. Seven eyes underwent surgical procedures; the remainder were observed. Final visions ranged from 20/20 to count fingers, with 3/13 (23%) having 20/200 or worse vision. Six eyes (46%) improved by two or more lines by the last follow-up. CONCLUSION: Soccer ball-related ocular injuries disproportionately affect young players, are more frequent in females than previously reported, and have more severe visual consequences than previously recognized. Injury prevention strategies to minimize contact between the eye and the soccer ball may reduce the incidence and severity of eye injuries.

Adolescent↗
PubMed2000

Fas mediates apoptosis and oxidant-induced cell death in cultured hRPE cells.

PURPOSE: To investigate whether Fas ligand (FasL) and the Fas receptor system mediates apoptosis in cultured human retinal pigment epithelial (hRPE) cells and contributes to oxidant-induced death of hRPE cells. METHODS: Expression of FasL and Fas in cultured hRPE cells was examined by Western blot analysis and flow cytometry. The susceptibility of hRPE cells to Fas-mediated apoptosis was determined by incubating cells with recombinant soluble Fas ligand (sFasL). Characteristics of apoptosis assessed included chromatin condensation, DNA cleavage, and phosphatidylserine exposure. To investigate the possible involvement of Fas-mediated apoptosis in oxidative killing of hRPE cells, the effects of the oxidant tert-butylhydroperoxide (tBH) on the expression of FasL and Fas were studied. The specificity of effects of oxidant was examined using the antioxidants glutathione and N-acetyl-L-cysteine (NAC). The requirement for the Fas pathway in tBH-induced apoptosis was investigated using an antagonistic anti-Fas antibody ZB4 that blocks the interaction between FasL and Fas. RESULTS: Cultured hRPE cells constitutively expressed FasL and Fas. Ligation of Fas receptor with recombinant sFasL triggered apoptosis in hRPE cells. tBH treatment of hRPE cells resulted in increased expression of FasL and Fas. Glutathione and NAC completely abrogated tBH-induced increase in FasL and Fas expression and apoptosis. Blocking FasL and Fas interaction by ZB4 inhibited tBH-induced apoptosis, but only partially. CONCLUSIONS: A functional Fas-mediated apoptotic pathway is present in cultured hRPE cells and can be activated with sFasL or by upregulation of FasL and Fas expression with an oxidant. The incomplete inhibition by blocking antibody indicates that the Fas pathway is involved in oxidant-induced apoptosis, but other triggering mechanisms are also important.

Acetylcysteine↗
PubMed1999

Oxidative damage and age-related macular degeneration.

This article provides current information on the potential role of oxidation in relation to age-related macular degeneration (AMD). The emphasis is placed on the generation of oxidants and free radicals and the protective effects of antioxidants in the outer retina, with specific emphasis on the photoreceptor cells, the retinal pigment epithelium and the choriocapillaris. The starting points include a discussion and a definition of what radicals are, their endogenous sources, how they react, and what damage they may cause. The photoreceptor/pigment epithelium complex is exposed to sunlight, is bathed in a near-arterial level of oxygen, and membranes in this complex contain high concentrations of polyunsaturated fatty acids, all considered to be potential factors leading to oxidative damage. Actions of antioxidants such as glutathione, vitamin C, superoxide dismutase, catalase, vitamin E and the carotenoids are discussed in terms of their mechanisms of preventing oxidative damage. The phototoxicity of lipofuscin, a group of complex autofluorescent lipid/protein aggregates that accumulate in the retinal pigment epithelium, is described and evidence is presented suggesting that intracellular lipofuscin is toxic to these cells, thus supporting a role for lipofuscin in aging and AMD. The theory that AMD is primarily due to a photosensitizing injury to the choriocapillaris is evaluated. Results are presented showing that when protoporphyric mice are exposed to blue light there is an induction in the synthesis of Type IV collagen synthesis by the choriocapillary endothelium, which leads to a thickened Bruch's membrane and to the appearance of sub-retinal pigment epithelial fibrillogranular deposits, which are similar to basal laminar deposits. The hypothesis that AMD may result from oxidative injury to the retinal pigment epithelium is further evaluated in experiments designed to test the protective effects of glutathione in preventing damage to cultured human pigment epithelial cells exposed to an oxidant. Experiments designed to increase the concentration of glutathione in pigment epithelial cells using dimethylfumarate, a monofunctional inducer, are described in relation to the ability of these cells to survive an oxidative challenge. While all these models provide undisputed evidence of oxidative damage to the retinal pigment epithelium and the choriocapillaris that is both light- and oxygen-dependent, it nevertheless is still unclear at this time what the precise linkage is between oxidation-induced events and the onset and progression of AMD.

Antioxidants↗
PubMed1999

Surgical management of subfoveal neovascularization in children.

OBJECTIVE: To report the authors' clinical experience with submacular surgery for subfoveal membranes in children and to evaluate the histopathologic findings of membranes in children with various etiologies of choroidal neovascularization. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Twelve eyes of 12 consecutive children with subfoveal choroidal neovascularization treated by vitrectomy and excision of the choroidal neovascular complex. INTERVENTION: Vitrectomy, excision of the choroidal neovascular complex, and air-fluid exchange. MAIN OUTCOME MEASURES: Visual acuity and recurrence of choroidal neovascular membrane. RESULTS: Preoperative visual acuities ranged from 20/60 to 20/800 (median, 20/300). Postoperative visual acuities ranged from 20/25 to 20/400 (median, 20/80) after an average follow-up of 20 months (range, 7-62 months). Ten of 12 eyes improved from immediate preoperative visual acuity, and four eyes developed recurrence of neovascular membranes over a mean follow-up of 18 months. Histopathologic examination of six excised membranes showed that the most common components of the membranes were retinal pigment epithelium, fibrocytes, vascular endothelium, and collagen. CONCLUSION: Selected eyes of children with subfoveal neovascular membranes and no evidence of membrane regression may benefit from submacular surgery. The histopathologic findings were similar to adult choroidal neovascularization not associated with age-related macular degeneration.

Adolescent↗