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Biomedical subjects

R M Feldman

Publications and source records attributed to R M Feldman.

At least 37 records · Page 2Linked to original sources

The MHC class I homolog encoded by human cytomegalovirus binds endogenous peptides.

The ability of a human cytomegalovirus-encoded homolog of MHC class I molecules to serve as a peptide receptor was investigated. Sequencing of peptide material eluted from the purified viral protein revealed a mixture of endogenous peptides with characteristics similar to those eluted from conventional class I molecules, that is, anchor residues, and a predominance of short peptides derived from cytoplasmic proteins. The possible function(s) of this viral MHC homolog are discussed in light of the finding that it binds endogenous peptides.

Amino Acid Sequence↗

Picosecond neodymium:yttrium lithium fluoride (Nd:YLF) laser peripheral iridotomy.

PURPOSE: We evaluated the picosecond neodymium:yttrium lithium fluoride (Nd:YLF) laser for performing peripheral iridotomies of predetermined size and shape in various types of irides. METHODS: In the first part of the study, we determined operating parameters from performing 60 iridotomies in human cadaver eyes. Subsequently, using the parameters obtained in cadaver eyes, iridotomies were created in eyes of patients with primary angle-closure glaucoma. RESULTS: In the cadaver eyes, the optimal parameters were a rectangular cutting pattern of 0.3 x 0.3 mm, 500-microns cutting depth, 50-microns spot separation, 200 to 400 microJ of energy per pulse, 200 to 400 pulses per second, and no focal offset distance. In 18 eyes of 11 patients, iridotomies with well-defined margins and size were created. Minimal hemorrhage occurred intraoperatively in ten of 18 eyes (55.6%), which did not affect the outcome of the procedure. Increases of postoperative intraocular pressure at one hour averaged 3.5 +/- 5.1 mm Hg, with an increase of more than 10 mm Hg in three eyes (16.7%), and a maximum of 12 mm Hg. We observed no corneal or retinal damage. CONCLUSION: The picosecond Nd:YLF laser seems to be an effective instrument for reliably performing peripheral iridotomies of precise size and shape using low energy per pulse levels. This laser, unlike the argon laser, is successful independent of iris thickness or color and can easily make a larger iridotomy than is often possible with the Nd:YAG laser.

Adult↗

Intraocular pressure elevation associated with inhalation and nasal corticosteroids.

BACKGROUND: The ocular hypertensive response to corticosteroids is well established. Elevated intraocular pressure (IOP) secondary to corticosteroids by nasal spray or inhalation has rarely been reported. RESULTS: Three patients showed a possible ocular hypertensive response to beclomethasone dipropionate by nasal spray or inhalation. In two patients, the IOP returned to pretreatment levels after discontinuing nasal corticosteroid spray. One patient required medication to control IOP with continued inhaled corticosteroid. One patient later demonstrated an ocular hypertensive response to oral steroids. CONCLUSION: Corticosteroids by nasal spray or inhalation may cause ocular hypertension in susceptible patients. The authors recommend surveillance of IOP in patients using these medications.

Administration, Inhalation↗

Engineering and expression of a secreted murine TCR with reduced N-linked glycosylation.

Structural studies of TCR-alpha beta heterodimers would be greatly aided by the ability to produce nonchimeric, secreted material with less carbohydrate heterogeneity. Here, we report the engineering and expression of variants of the murine TCR 2B4 in which many of the potential N-linked glycosylation sites were eliminated. Specific truncations proximal to the transmembrane region were also introduced that result in a secreted heterodimer. Although elimination of N-linked oligosaccharide on the beta-chain does not significantly affect the expression levels of 2B4 heterodimers, ablation of N-linked oligosaccharide on the alpha-chain results in a measurable reduction in expression levels of membrane-associated molecules. Secreted forms of 2B4 heterodimers in which the N-linked glycosylation of the beta-chain has been eliminated can be expressed. The secreted receptor is shown by a variety of Ab determinants to be indistinguishable from native material.

Amino Acid Sequence↗

Effects of peptide length and composition on binding to an empty class I MHC heterodimer.

Class I major histocompatibility complex (MHC) proteins present peptide antigens to T cells during the immune response against viruses. Peptides are loaded into newly synthesized class I heterodimers in the endoplasmic reticulum such that most or all cell surface class I molecules contain peptides derived from endogenous or foreign proteins. We previously reported the assembly of empty heterodimers of the murine class I MHC molecule H-2Kd, from denatured heavy and light chains from which endogenous peptides had been removed [Fahnestock et al. (1992) Science 258, 1658-1662]. Here we measure thermal stability profiles of empty versus peptide-filled molecules and compare the effects of human versus murine light chains on the overall stability of the Kd heterodimer. The majority of empty heterodimers are stable at 37 degrees C regardless of the species of light chain, indicating that our previous report of the unexpectedly high thermal stability was an intrinsic property of the Kd molecule and not due to use of a murine/human chimeric protein. Binding constants are derived for a series of peptides interacting with empty Kd heterodimers. The dissociation constants of four known Kd-restricted peptides range from 2.3 x 10(-7) to 3.4 x 10(-8) M. Using a series of 24 analog peptides, the effects of length and peptide composition on binding affinity of one Kd-restricted peptide are explored, and the results are interpreted with reference to the known three-dimensional structures of class I MHC protein/peptide complexes.

Amino Acid Sequence↗

A human cadaver eye model for anterior and posterior segment laser applications.

We have developed a cadaver eye model that allows anterior and posterior segment laser procedures to be performed under closely simulated in vivo conditions. The model consists of a reusable container with an artificial cornea with a refractive power and an anterior radius of curvature similar to those of the human cornea, and a fresh cadaver eye, prepared by removing the cornea and adjusting the biometric parameters to normal values. This cadaver eye model appears to be a valuable tool for teaching and practicing anterior and posterior segment laser procedures, as well as for research on new laser systems and applications.

Anterior Eye Segment↗

Visual outcome in acute retinal necrosis.

Acute retinal necrosis (ARN) is generally a progressive retinitis, often complicated by retinal detachment and a poor visual outcome. A series of 12 consecutive patients (13 eyes) with ARN is reported. All patients were examined early, with a limited extent of disease (in 77% of the eyes, less than 25% of retina involved). Patients were treated with high-dose intravenous acyclovir (10 mg/kg every 8 hours) and laser photocoagulation. During a follow-up period of 3 to 21 months, only 1 patient developed a rhegmatogenous retinal detachment resulting in visual loss. No patients developed bilateral disease once intravenous antiviral therapy was begun. Final visual acuity was 20/40 or better in 6 eyes (46%), and 20/400 or better in 12 eyes (92%). Two patients were examined within 6 weeks of extracapsular cataract extraction with intraocular lens implantation. In the majority of the cases, clinical findings were limited to several quadrants of the peripheral retina. Eyes with limited disease, if aggressively treated, have a relatively good visual prognosis.

Acyclovir↗

Collagen plug occlusion of Molteno tube shunts.

We report five patients in whom collagen lacrimal plugs were used to temporarily occlude the lumen of Molteno shunts to prevent early postoperative hypotony. Only one eye, with a double plate, developed hypotony and a flat anterior chamber that required reformation. However, in three patients, the collagen plugs did not dissolve and had to be removed surgically to lower the intraocular pressure. Although the semipermeability of collagen is desirable, its unpredictable degradation renders it unsuitable for temporary occlusion of tube shunts. Other biodegradable materials may be more appropriate for this purpose.

Aged↗

Running nylon suture dissolution after penetrating keratoplasty.

We attempted to evaluate whether the low degrees of astigmatism achieved early in the postkeratoplasty period with the combined interrupted/running suturing technique were maintained for long periods of time. For 13 to 70 months (mean, 30.2 months), we monitored a group of patients (25 eyes) who had previously undergone the combined interrupted/running suturing technique (12 interrupted 10-0 nylon sutures and one running 11-0 nylon suture). Nine running sutures broke spontaneously, causing a significant increase of the keratometric astigmatism of the entire population from 1.7 +/- 1.6 to 3.4 +/- 2.6 diopters (mean +/- standard deviation). The mean vector-corrected change in astigmatism after suture breakage was 4.9 +/- 2.6 diopters. Surgical procedures to reduce astigmatism were required in many of the eyes in which the 11-0 running nylon suture broke. Our results suggested that 11-0 nylon is not an ideal material for the running suture because its high rate of spontaneous disruption leads to undesired, statistically significant increases in postkeratoplasty astigmatism. Further, our results indicated that the selective suture technique can maintain low degrees of astigmatism only if the sutures remain intact. Studies of the effect of keratoplasty suturing techniques on astigmatism should probably include a follow-up that is sufficiently long to indicate its long-term value to the patient.

Adult↗

Intraoperative application of 5-fluorouracil during trabeculectomy.

We report the preliminary results of the first 20 consecutive cases in which the antimetabolite 5-fluorouracil (5-FU) was applied directly beneath the conjunctival flap during trabeculectomy in high-risk patients. Seventeen were considered early successes, with 3-month postoperative intraocular pressures less than 21 mmHg, representing at least a 20% decrease from preoperative values. Successful blebs were pale, with conjunctival microcysts and without significant vascularization over the trabeculectomy site, similar to the appearance of blebs in eyes administered postoperative subconjunctival injections of 5-FU. There were no cases of corneal epithelial defects, and no eyes had lost more than one line of preoperative vision at the time of last follow up. Although the longer term efficacy of this method is unknown, these results suggest that it may represent a safe and effective alternative for administering 5-FU.

Adult↗

Long-term efficacy of repeat argon laser trabeculoplasty.

The role of repeat argon laser trabeculoplasty (RALT) in the management of open-angle glaucoma is controversial. To determine the long-term efficacy of RALT, the authors reviewed case records of 44 patients (50 eyes) who received RALT for uncontrolled glaucoma at the Wills Eye Hospital before 1986. Success was defined as a 3 mmHg or greater decrease in intraocular pressure (IOP) to less than 22 mmHg, and no further surgical intervention. By life table analysis, RALT was successful in 35% of eyes at 6 months, in 21% at 12 months, in 11% at 24 months, and in 5% at 48 months. Thirty-three percent of eyes in which primary ALT was successful for 1 year were successful 12 months after RALT. Complications included IOP spikes in 12%. In conclusion, RALT was generally not effective for long-term control of open-angle glaucoma, but may be useful as a temporizing measure. However, this use of RALT must be weighed against the risks of complications and the additional progression of disease before more definitive surgical intervention.

Adult↗

Risk factors for the development of Tenon's capsule cysts after trabeculectomy.

Tenon's capsule cysts (TCCs) are a complication of glaucoma filtering surgery. They are frequently associated with substantial elevations in intraocular pressure (IOP) beginning 2 to 8 weeks postoperatively. To determine the incidence and possible risk factors for the development of TCCs, case records of all patients who received trabeculectomy over a 4-year period at the Wills Eye Hospital were reviewed. The incidence of TCCs was 28% in those who underwent trabeculectomy. Characteristics of patients after trabeculectomy in whom TCCs developed were compared with patients after trabeculectomy in whom TCCs did not develop. Both univariate and multivariate techniques were used to assess the association of characteristics associated with the development of TCCs. Factors associated with increased risk (P less than 0.05) were: history of prior TCCs, argon laser trabeculoplasty, male gender, and the use of preoperative sympathomimetics. The use of a compression shell was associated with decreased risk (P less than 0.05).

Adult↗