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Biomedical subjects

R M Feldman

Publications and source records attributed to R M Feldman.

At least 19 recordsLinked to original sources
PubMed2001

Net1 stimulates RNA polymerase I transcription and regulates nucleolar structure independently of controlling mitotic exit.

The budding yeast RENT complex, consisting of at least three proteins (Net1, Cdc14, Sir2), is anchored to the nucleolus by Net1. RENT controls mitotic exit, nucleolar silencing, and nucleolar localization of Nop1. Here, we report two new functions of Net1. First, Net1 directly binds Pol I and stimulates rRNA synthesis both in vitro and in vivo. Second, Net1 modulates nucleolar structure by regulating rDNA morphology and proper localization of multiple nucleolar antigens, including Pol I. Importantly, we show that the nucleolar and previously described cell cycle functions of the RENT complex can be uncoupled by a dominant mutant allele of CDC14. The independent functions of Net1 link a key event in the cell cycle to nucleolar processes that are fundamental to cell growth.

Animals↗
PubMed2001

Control of intra-ocular inflammation associated with cataract surgery.

Postoperative ocular inflammation following cataract surgery is related to the risk of complications like corneal edema, intraocular pressure spikes, cystoid macular edema, and posterior capsule opacification. The degree of postoperative inflammation following cataract surgery is linked to several surgery-dependent factors such as surgical technique, intraocular lens type, and also patient-dependent factors such as history of inflammatory disease and degree of iris pigmentation. During the past decade, major advances have occurred in cataract surgery techniques, equipment, and pharmacologic strategies that decrease the degree of postoperative inflammation following cataract surgery and reduce patients' risk for inflammation-related complications. This article reviews the most recent literature regarding the control of cataract surgery-induced intra-ocular inflammation.

Cataract Extraction↗
PubMed2001

Bleb window cryopexy for the management of oversized, misplaced blebs.

PURPOSE: To describe a new technique for revising oversized blebs after trabeculectomy. METHODS: A chart review of consecutive patients undergoing bleb window cryopexy was conducted. Patients with symptomatic oversized blebs were candidates for the technique, regardless of the intraocular pressure. Under topical anesthesia, the bleb was incised and a 3 mm x 3 mm conjunctival window was removed using 0.12 forceps and Vannas scissors. Light cryotherapy was applied to the sclera through the window. A soft bandage contact lens was then placed for compression, and a patch was applied. All patients were given antibiotic drops the first day after surgery. Topical corticosteroid drops were used to minimize postoperative inflammation. Outcome measures included relief of symptoms, adequate control of intraocular pressure, and restoration of filtering bleb function without further antiglaucoma medication or surgical bleb revision. RESULTS: Nine patients met the inclusion criteria. All patients had flattening of the bleb with symptomatic relief within 2 weeks. No loss of bleb function occurred. One patient developed aqueous misdirection after the procedure. CONCLUSION: Early results showed that bleb window cryopexy is safe and effective. This minimally invasive technique can be useful for selected patients with large. symptomatic, overhanging blebs.

Aged↗
PubMed2000

Autologous conjunctival resurfacing of leaking filtering blebs.

PURPOSE: To present a case series of a new technique to repair late bleb leaks. DESIGN: Retrospective, noncomparative, consecutive case series. PARTICIPANTS: Forty-seven autologous conjunctival resurfacings of late bleb leaks were performed by four surgeons at two institutions. METHODS: Autologous conjunctival grafts were placed over existing de-epithelialized leaking blebs. MAIN OUTCOME MEASURES: Leak-free, Seidel-negative blebs and controlled glaucoma. RESULTS: After a mean follow-up of 14 +/- 12 months, one patient continued to have bleb leak at the last follow-up, and one frank leak resolved with aqueous suppression. Intraocular pressure increased from 6.6 +/- 4.4 mmHg (0.13 glaucoma medications) to 11.9 +/- 4.1 mmHg (0.41 glaucoma medications). CONCLUSIONS: Conjunctival resurfacing with autologous tissue is an effective technique to repair late bleb leaks.

Adolescent↗
PubMed2000

Efficacy of preoperative versus postoperative ketorolac tromethamine 0.5% in reducing inflammation after cataract surgery.

PURPOSE: To compare the efficacy of 30 minute preoperative versus 1 day postoperative administration of ketorolac tromethamine 0.5% ophthalmic solution (Acular) in reducing anterior chamber inflammation after cataract surgery. SETTING: The Hermann Eye Center, The University of Texas Health Science Center-Houston, Texas, USA. METHODS: Fifty eyes of 48 consecutive patients scheduled for phacoemulsification with intraocular lens implantation were included. Before surgery, patients were randomly assigned to start the study drug 30 minutes preoperatively or 1 day postoperatively. No other antiinflammatory agents were used intraoperatively or postoperatively. Main outcome measures were flare and cell counts. RESULTS: Preoperative and postoperative flare and cell counts did not differ significantly between the 2 treatment groups at any time. Both groups showed significant increases in flare (P =.0001) and cells (P =.0001) 1 day postoperatively. Flare and cells returned to baseline levels by day 28 in both groups. There was no significant difference at any time between the 2 groups in the change from the preoperative level of inflammation. CONCLUSIONS: There was no difference between administering ketorolac 30 minutes preoperatively versus 1 day postoperatively in reducing inflammation.

Adult↗
PubMed2000

Effects of atropine on anterior chamber depth and anterior chamber inflammation after primary trabeculectomy.

PURPOSE: To investigate the effects of postoperative atropine on central and peripheral anterior chamber depth and anterior chamber inflammation in patients undergoing primary trabeculectomy. METHODS: Two separate groups of patients who were phakic without previous intraocular surgery undergoing primary trabeculectomy were prospectively randomized to atropine or no atropine. In the first group of patients, 24 eyes of 21 patients undergoing primary trabeculectomy were prospectively randomized to atropine or no atropine, and their anterior chamber depth was measured. Central and peripheral chamber depths were measured using the EAS-1000 anterior segment analysis system (Nidek, Tokyo, Japan) before surgery and on postoperative days 1, 3, 7, 14, and 30. In the second group, 34 patients undergoing primary trabeculectomy were prospectively randomized to atropine or no atropine, and their anterior chamber reaction was documented. The amount of cells and flare was measured using the Kowa laser flare meter (FM-500) and cell counter (LC-500) (Kowa Electronics and Optics, Tokyo, Japan) preoperatively and on postoperative day 1, 7, and 30. RESULTS: Compared with preoperative measurements, a small (approximately 0.1 mm) but statistically significant deepening of the central and peripheral anterior chamber depth on days 1, 7, 14, and 30 was found in patients who used atropine. In the nonatropine group, no statistically significant change was found in central or peripheral anterior chamber depths at any time as compared with preoperative values. There was no statistically significant difference in the cell or flare counts between the atropine and nonatropine groups at any time. CONCLUSIONS: This study showed a small but statistically significant deepening of the anterior chamber with atropine. No statistically significant differences were observed in the cell or flare counts between atropine and nonatropine groups. Routine atropine use after trabeculectomy may not be necessary to reduce postoperative complications, such as shallowing of the anterior chamber or anterior chamber inflammation. In patients with a shallow anterior chamber, however, atropine would be expected to deepen the chamber.

Adolescent↗
PubMed1999

Cdc53/cullin and the essential Hrt1 RING-H2 subunit of SCF define a ubiquitin ligase module that activates the E2 enzyme Cdc34.

SCFCdc4 (Skp1, Cdc53/cullin, F-box protein) defines a family of modular ubiquitin ligases (E3s) that regulate diverse processes including cell cycle, immune response, and development. Mass spectrometric analysis of proteins copurifying with Cdc53 identified the RING-H2 finger protein Hrt1 as a subunit of SCF. Hrt1 shows striking similarity to the Apc11 subunit of anaphase-promoting complex. Conditional inactivation of hrt1(ts) results in stabilization of the SCFCdc4 substrates Sic1 and Cln2 and cell cycle arrest at G1/S. Hrt1 assembles into recombinant SCF complexes and individually binds Cdc4, Cdc53 and Cdc34, but not Skp1. Hrt1 stimulates the E3 activity of recombinant SCF potently and enables the reconstitution of Cln2 ubiquitination by recombinant SCFGrr1. Surprisingly, SCF and the Cdc53/Hrt1 subcomplex activate autoubiquitination of Cdc34 E2 enzyme by a mechanism that does not appear to require a reactive thiol. The highly conserved human HRT1 complements the lethality of hrt1Delta, and human HRT2 binds CUL-1. We conclude that Cdc53/Hrt1 comprise a highly conserved module that serves as the functional core of a broad variety of heteromeric ubiquitin ligases.

Amino Acid Sequence↗
PubMed1999

Consensual inflammation following ocular surgery.

PURPOSE: To determine whether a consensual inflammatory response occurs following unilateral phacoemulsification or trabeculectomy in humans. METHODS: Sixty patients undergoing phacoemulsification or primary trabeculectomy were included in the study. Some patients were randomly assigned to have a shield placed on the non-operated eye during surgery. The Kowa laser flare meter (FM-500) and laser cell counter (LC-500) (Kowa Electronics and Optics, Tokyo, Japan) were used to assess the inflammatory response in both eyes. Measurements were taken preoperatively and on postoperative days 1, 7 and 28. The regression analysis with random model effect was used to identify factors which may affect the change of flare and cells in the non-operated eye after surgery. Correlation was evaluated between the inflammatory responses of the paired eyes. A P<0.05 was considered statistically significant for all analyses. RESULTS: The flare and cells in the non-operated eye showed a small, but significant, increase on day 1 (mean flare increased 2.68 photons/ms from preoperative level with P<0.001 and mean cells increased 2.49 cells/0.5 mm3 from preoperative level with P<0.0001). At day 7 the amount of inflammation was still elevated (mean flare increased 0.41 photons/ms from preoperative level with P<0.001 and mean cells increased 0.63 cells/0.5 mm3 from preoperative level with P<0.001). By day 28, the amount of inflammation in the nonoperated eyes returned to preoperative levels. CONCLUSIONS: Subclinical inflammation occurs in the non-operated eye following phacoemulsification and trabeculectomy. The etiology of this finding has yet to be elucidated.

Adult↗
PubMed1999

Low-dose postoperative transconjunctival application of mitomycin C in rabbit trabeculectomy.

PURPOSE: Mitomycin C (MMC) is commonly administered during filtering surgery to enhance the success of the procedure. Unfortunately, the increased success rate is associated with complications, including late bleb leaks, endophthalmitis, and ciliary epithelial toxicity. The purpose of this study was to investigate a safe and effective dose regimen for MMC to reduce incidence of those complications. METHODS: Trabeculectomy was performed in 36 rabbits. MMC was applied only during surgery, only one day after surgery, or once daily after surgery for 3 days at lower concentrations. Balanced salt solution (BSS) was administered during surgery to one group as a placebo. The time to bleb failure was determined and the eyes were evaluated histopathologically. Success and toxicity were compared for the different treatment groups. RESULTS: The mean time until trabeculectomy failure was 2.83 days for the placebo group, 6.33 days with administration of MMC 0.5 mg/mL during surgery, 7.83 days with administration of MMC 0.5 mg/mL once after surgery, and 11, 9, and 4.83 days with administration of MMC 0.1 mg/mL, 0.05 mg/mL, or 0.025 mg/mL, respectively, once a day for 3 consecutive days. On electron microscopic examination of the ciliary epithelium, toxic effects were greatest with MMC concentrations of 0.5 mg/mL and were less with lower concentrations. CONCLUSION: The effect of MMC on trabeculectomy survival was dependent on both the concentration and the method of administration. Lower concentrations with multiple postoperative administrations were as effective as but caused less ciliary body toxicity than intraoperative administration of higher concentrations.

Alkylating Agents↗
PubMed1998

Suramin inhibits wound healing following filtering procedures for glaucoma.

BACKGROUND: Trabeculectomies are the most frequently performed procedures in surgically treating eyes with glaucoma. Failures are caused by fibrosis in the external ostium of the filtering procedure. In order to inhibit the fibrotic wound healing reaction, a new pharmacological approach using suramin, which inhibits a variety of important growth factors was used. METHODS: Pigmented rabbits were used and filtering procedures performed. Suramin was applied with concentrations ranging from 10 mg/ml to 333 mg/ml once during surgery and four times following surgery. The success of the filtering procedure was assessed by intraocular pressure measurements. To evaluate possible intraocular toxic effects, treated eyes were histopathologically evaluated after 4 weeks, and the ciliary body adjacent to the site of application was examined using electron microscopy. RESULTS: With concentrations of suramin of 200 mg/ml and 333 mg/ml, the trabeculectomies were patent longer than in the controls and in eyes operated with mitomycin C, which currently is the most frequently used antiproliferative drug to enhance the outcome of surgery in humans. No severe toxic effects to the ciliary epithelium were seen in suramin treated eyes. CONCLUSIONS: This study demonstrates for the first time the efficiency of a substance that broadly inhibits the action of growth factors on target cells in the setting of ocular wound healing. In this in vivo model, suramin has been shown to be highly effective in preventing scarring and in having fewer toxic side effects than usually used antimetabolites. These results therefore may suggest a new approach to the surgical treatment of glaucoma.

Animals↗
PubMed1998

Reproducibility of the laser flare meter and laser cell counter in assessing anterior chamber inflammation following cataract surgery.

BACKGROUND AND OBJECTIVES: To determine the interobserver and intraobserver reproducibility of the laser flare meter and laser cell counter in assessing anterior chamber inflammation following cataract surgery. PATIENTS AND METHODS: Thirty-nine eyes with varied degrees of inflammation and 9 normal eyes were included in the study. Anterior chamber flare and cells were evaluated with the slit lamp and graded on a scale of 0 to 4+. The flare and cells were then measured three times each using the flare meter and cell counter by two different, experienced observers. The intraobserver reproducibilities were computed to evaluate repeatability of the instruments operated by the same observer. The first measurement taken by each observer was used to assess reproducibility between the two observers. RESULTS: The intraobserver reproducibility for overall flare was 0.995 for both observers. The intraobserver reproducibility for overall cells was 0.996 for observer 1 and 0.991 for observer 2. The overall interobserver reproducibility was 0.994 for flare and 0.988 for cells. The correlation between measurements and slit-lamp ratings was 0.78 for flare and 0.56 for cells. CONCLUSIONS: The intraobserver and interobserver reproducibilities were excellent, with good correlation to slit-lamp measurements. Reproducible results can be obtained using the laser flare meter and the laser cell counter. It is not known whether these results are applicable to other inflammatory processes with higher grades of flare and cells and with different protein and cell types.

Anterior Chamber↗
PubMed1998

A randomized double-masked trial comparing ketorolac tromethamine 0.5%, diclofenac sodium 0.1%, and prednisolone acetate 1% in reducing post-phacoemulsification flare and cells.

BACKGROUND AND OBJECTIVE: To compare the efficacy of ketorolac tromethamine 0.5%, diclofenac sodium 0.1%, and prednisolone acetate 1% in reducing flare and cells following cataract surgery. PATIENTS AND METHODS: Fifty-eight patients undergoing phacoemulsification with posterior chamber intraocular lens implantation were randomly selected to receive either ketorolac tromethamine 0.5%, diclofenac sodium 0.1%, or prednisolone acetate 1% following surgery. The treatment regimen was 1 drop 4 times a day for 1 week, then twice a day for the next 3 weeks. Flare, cells, and intraocular pressures (IOPs) were measured preoperatively and on postoperative days 1, 7, and 28. RESULTS: No statistically significant differences in either actual flare or cell counts or in change in flare or cell counts from baseline were detected among the three groups. No statistically significant differences in IOP or in change of IOP from preoperative measurements were detected. No medication-related complications were noted at any time. CONCLUSION: Ketorolac tromethamine 0.5% and diclofenac sodium 0.1% may be as effective and as safe as prednisolone acetate 1% in controlling inflammation following cataract extraction.

Adult↗
PubMed1998

Semiconductor diode laser transscleral cyclophotocoagulation in a patient with glaucoma secondary to metastatic tumor to the iris.

PURPOSE: Management of a case of glaucoma secondary to an iris metastasis is reported. RESULTS: A 31-year-old woman developed glaucoma secondary to a metastatic tumor to the iris. Anti-glaucoma medication failed to control the increase in intraocular pressure (IOP). However, diode laser cyclophotocoagulation controlled the IOP. CONCLUSION: Glaucoma secondary to an iris metastasis is difficult to manage. Diode laser cyclophotocoagulation is effective in controlling the increase in IOP without affecting visual acuity.

Adult↗
PubMed1997

A complex of Cdc4p, Skp1p, and Cdc53p/cullin catalyzes ubiquitination of the phosphorylated CDK inhibitor Sic1p.

In S. cerevisiae, the G1/S transition requires Cdc4p, Cdc34p, Cdc53p, Skp1p, and the Cln/Cdc28p cyclin-dependent kinase (Cdk). These proteins are thought to promote the proteolytic inactivation of the S-phase Cdk inhibitor Sic1p. We show here that Cdc4p, Cdc53p, and Skp1p assemble into a ubiquitin ligase complex named SCFCdc4p. When mixed together, SCFCdc4p subunits, E1 enzyme, the E2 enzyme Cdc34p, and ubiquitin are sufficient to reconstitute ubiquitination of Cdk-phosphorylated Sic1p. Phosphorylated Sic1p substrate is specifically targeted for ubiquitination by binding to a Cdc4p/Skp1p subcomplex. Taken together, these data illuminate the molecular basis for the G1/S transition in budding yeast and suggest a general mechanism for phosphorylation-targeted ubiquitination in eukaryotes.

Animals↗
PubMed1997

SIC1 is ubiquitinated in vitro by a pathway that requires CDC4, CDC34, and cyclin/CDK activities.

Traversal from G1 to S-phase in cycling cells of budding yeast is dependent on the destruction of the S-phase cyclin/CDK inhibitor SIC1. Genetic data suggest that SIC1 proteolysis is mediated by the ubiquitin pathway and requires the action of CDC34, CDC4, CDC53, SKP1, and CLN/CDC28. As a first step in defining the functions of the corresponding gene products, we have reconstituted SIC1 multiubiquitination in DEAE-fractionated yeast extract. Multiubiquitination depends on cyclin/CDC28 protein kinase and the CDC34 ubiquitin-conjugating enzyme. Ubiquitin chain formation is abrogated in cdc4ts mutant extracts and assembly restored by the addition of exogenous CDC4, suggesting a direct role for this protein in SIC1 multiubiquitination. Deletion analysis of SIC1 indicates that the N-terminal 160 residues are both necessary and sufficient to serve as substrate for CDC34-dependent ubiquitination. The complementary C-terminal segment of SIC1 binds to the S-phase cyclin CLB5, indicating a modular structure for SIC1.

Anaphase-Promoting Complex-Cyclosome↗
PubMed1997

Valve membrane adhesion as a cause of Ahmed glaucoma valve failure.

PURPOSE: The purpose of this study was to describe a possible mechanism of failure of the Ahmed glaucoma valve (AGV; New World Medical, Rancho Cucamonga, CA). METHOD: Two AGVS that failed to control intraocular pressure (IOP) were examined. In vivo examination consisted of unroofing the capsule surrounding the implant and injecting fluorescein-stained balanced salt solution into the tube. In one case the entire implant was removed and examined in vitro, and in the other case only the valve portion was removed. RESULT: No flow in either case extended beyond the valve. In both cases, the membrane valve system was found to be fused and could not be pulled apart. CONCLUSION: Failure of the AGV may occur due to adhesion of the valve membranes.

Anterior Chamber↗
PubMed1997

Visual function following trabeculectomy: effect on corneal topography and contrast sensitivity.

PURPOSE: This study was to determine the role of changes in refractive error, contrast sensitivity, and corneal topography in transient changes in visual function following trabeculectomy. METHODS: We performed a prospective study evaluating these factors in 13 consecutive patients undergoing a standardized trabeculectomy. Preoperatively, and at 1, 4, and 12 weeks postoperatively, we measured best-corrected visual acuity, refractive error, and contrast sensitivity and analyzed computerized video-keratographic studies including estimated corneal visual acuity. RESULTS: One week postoperatively, best-corrected visual acuity decreased at least one line in 8 of 13 patients, whereas no eyes had decreased contrast sensitivity. Mean central corneal astigmatism increased 1.4 diopters along the surgical meridian. By 12 weeks, visual acuity returned to preoperative levels in all patients and the corneal topographic changes returned to within 1 diopter of preoperative values in 12 of 13 patients. Postoperative changes in estimated corneal visual acuity were similar to those in best-corrected visual acuity with no statistically significant difference. CONCLUSIONS: Corneal topographic changes appear to contribute to visual acuity reduction following trabeculectomy. In most cases this is transient with return to preoperative topography within 12 weeks.

Aged↗