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Biomedical subjects

M Sears

Publications and source records attributed to M Sears.

At least 19 recordsLinked to original sources
PubMed1996

Spontaneous and evoked oscillations of cytosolic calcium in the freshly prepared ciliary epithelial bilayer of the rabbit eye.

Under confocal microscopy, calcium imaging of the isolated secretory ciliary epithelium, especially the inner layer, non-pigmented epithelium (NPE), revealed spontaneous calcium oscillations in multiple patterns. Oscillations induced by stimulation of the muscarinic receptor have an onset that coincides with synthesis and release of InsP3. Caffeine (5 mM) induced a calcium transient and blocked spontaneous and (0.1 mM) muscarine induced oscillations. Thapsigargin (1 microM) prevented a muscarinic response. Muscarine and caffeine induced transients have significantly greater amplitude in NPE than in PE (outer layer, pigmented epithelium). Calcium transients and frequencies of spontaneous oscillations are greater in NPE than PE. In NPE muscarine induced oscillations are observed with higher frequencies than the spontaneous ones: gamma-0.24 +/- 0.05Hz (8) versus 0.08 +/- 0.01Hz (18). These repetitive responses, spontaneous and receptor coupled, reflect intracellular coding of information. A calcium signal may contribute to the regulation of aqueous humor formation.

Animals↗
PubMed1996

Postmortem diagnosis of Fusarium panophthalmitis by the polymerase chain reaction.

PURPOSE: We undertook this study to determine if a polymerase chain reaction-based test that we developed for the filamentary fungus, Fusarium, could be used to detect the organism in postmortem ocular tissues. METHODS: We applied the polymerase chain reaction to amplify a target fragment of Fusarium DNA from formalin-fixed ocular tissues from a patient with endogenous Fusarium panophthalmitis. RESULTS: By using the polymerase chain reaction-based test, we were able to amplify the target fragment of DNA from the infected eyes, but not from uninfected control eyes. CONCLUSIONS: The technique appears to hold promise to be a sensitive, specific, and rapid method of diagnosing Fusarium infections.

Blotting, Southern↗
PubMed1996

Transepithelial transport of ascorbic acid by the isolated intact ciliary epithelial bilayer of the rabbit eye.

The purpose of these experiments was to test whether the isolated intact epithelial bilayer derived from rabbit ciliary processes transports ascorbic acid and to what degree the transport rate in vitro corresponds to the in vivo process. The intact ciliary epithelial bilayer of the rabbit eye isolated by perfusion was mounted in a particularly constructed Ussing type chamber. Fluxes were measured by additions of 14C ascorbate to the hemichamber on either the pigmented epithelium (PE) or the nonpigmented epithelium (NPE) side where equal concentrations of ascorbate from .02 to 2.0 mM were present. Samples were taken at intervals thereafter and counted in a liquid scintillation counter. The experiments were done under short circuit conditions to avoid the possible influence of fluctuating currents upon the movement of ascorbate. Like the earlier iris ciliary body preparations, separation of ascorbate fluxes is also done by the isolated intact ciliary epithelial bilayer, and the transport of ascorbic acid proceeds by saturation kinetics. The uptake process is accomplished entirely by the pigmented epithelium (PE). The Km of the process is 0.97 mM, and Vmax was valued at 130 nM/L/hr. Thus, assuming an aqueous flow rate of 2 microliters/min, the transfer of ascorbic acid across the bilayer occurs at a rate required to maintain the ordinary millimolar concentration of ascorbic acid in the aqueous humor found in vivo.

Animals↗
PubMed1996

Regulation and bioelectrical effects of cyclic adenosine monophosphate production in the ciliary epithelial bilayer.

PURPOSE: To determine whether the intact isolated ciliary epithelial bilayer retains the alpha-2 and beta adrenergic receptor activation and interaction described for whole ciliary processes and whether this pure epithelial bilayer displays bioelectric parameters sensitive to alterations in cyclic adenosine Monophosphate (cAMP) production induced by adrenergic compounds. METHODS: The intact ciliary epithelial bilayer of the rabbit eye isolated by perfusion was mounted in a specially constructed Ussing-type chamber. The transepithelial potential difference and short-circuit current were monitored for effects induced by agents that stimulated or blocked (some did both) caMP production. Using a radioimmunoassay, the latter were studied in the pure epithelial bilayers and in whole ciliary processes. RESULTS: A reproducible increase in cAMP production and an increase in the short-circuit current induced in the bilayer by isoproterenol, a nonspecific beta adrenergic agonist, were both blocked by pretreatment with either timolol, a nonspecific beta adrenergic blocking agent, or with para-aminoclonidine, an alpha-2 agonist. Maximal stimulation of cAMP with forskolin in this pure isolated epithelial preparation yields a response that is 60% of the value found in whole processes, indicating that the latter tissue contains responsive sites that are nonepithelial, probably vascular, or perhaps stromal. The degree of inhibition of the beta adrenergic receptor by alpha-2 agonists was not very different in the two preparations. On the other hand, inhibition of the epithelial vasointestinal peptide receptor by neuropeptide Y or alpha-2 agonism was considerably heightened in the pure bilayered epithelial preparation. CONCLUSIONS: The isolated intact ciliary epithelial bilayer, when stimulated with beta adrenergic receptor agonists, vasointestinal peptide, or forskolin, produces increased cAMP and its transepithelial potential becomes hyperpolarized. These chemical and bioelectrical effects are prevented by pretreatment with either alpha-2 adrenergic agonists or beta adrenergic blocking agents. The results obtained in the isolated intact purely epithelial ciliary bilayer confirm that the ciliary epithelium is the source of adrenergic receptor activation and interaction and support the hypothesis that aqueous humor production is regulated by interactions between epithelial alpha-2 and beta adrenergic receptors.

Adrenergic alpha-Agonists↗
PubMed1990

Metabolic neuropathy.

In this article a review and summary of peripheral neuropathies secondary to metabolic disorders, affecting the lower extremity, have been presented. The clinical presentation of individual symptomatology is variable depending on the nature and chronicity of illness. The clinical features that the podiatric physician must recognize is weakness, sensory, and gait disturbances resulting from these syndromes. Some disorders are reversible if recognized and treated early in their course. Thus, a thorough general history and physical examination is required of all patients presenting with apparent podiatric symptomatology.

Diagnosis, Differential↗
PubMed1989

Adenylate cyclase stimulation and intraocular pressure reduction by forskolin analogs.

Forskolin and 18 chemical analogs of forskolin were assayed for stimulation of adenylate cyclase activity in vitro and for their effects on intraocular pressure (IOP) in vivo. Adenylate cyclase activity was determined with a preparation of corpora striata from male Wistar rats and test drug concentrations of 0.3 to 300 microM. IOP effect was monitored after a single topical ocular application of a 1% suspension of the test drug to male New Zealand albino rabbits. Significant reductions in IOP occurred with compounds which had potent cyclase stimulatory properties. Most compounds with little cyclase stimulatory effect produced little or no decrease in IOP. A 1-substituted morpholino-acetoxy derivative, which may be a prodrug metabolized to active form by corneal esterases, showed little cyclase stimulation in vitro but produced significant reductions in IOP.

Adenylyl Cyclases↗
PubMed1987

Patterns of early visual field loss in open-angle glaucoma.

We examined two groups of patients with primary open-angle glaucoma with distinctly different patterns of early visual field loss using two visual field indices: mean defect and loss variance. Patients were selected on the basis of visual field criteria only. Eight patients were selected for diffuse depression of the differential light sensitivity without localized scotomas (mean defect greater than 3.0 decibels, loss variance less than 10.0 decibels). Seven patients were selected for localized scotomas without diffuse depression of the differential light sensitivity (mean defect less than or equal to 3.0 decibels, loss variance greater than or equal to 20.0 decibels). Patients with diffuse depression manifested intraocular pressures that were higher (mean peak pressure +/- S.E.M., 27.6 +/- 1.2 mm Hg) than those with localized defects (22.4 +/- 1.4 mm Hg). The optic disk rim area of the localized loss group (mean +/- S.E.M., 1.02 +/- 0.15 mm2) was significantly smaller (P less than .05) than the disk rim area of the diffuse loss group (1.33 +/- 0.07 mm2). This difference was largely because of thinner temporal disk rims in the localized loss group. Different patterns of visual field loss may be caused by different mechanisms of glaucomatous optic nerve damage.

Aged↗
PubMed1987

Quantitative evaluation of the optic nerve head in patients with unilateral visual field loss from primary open-angle glaucoma.

Measurable structural alterations of the optic nerve head may precede visual field abnormalities in early open-angle glaucoma. The authors studied the optic nerve heads of 10 patients with unilateral visual field loss from primary open-angle glaucoma, and 12 age- and sex-matched normal subjects. Topographic optic nerve head parameters were measured with a system of computerized image analysis (Rodenstock Analyzer, G. Rodenstock Instrumente GMBH, Munich, W. Germany). In patients with asymmetric primary open-angle glaucoma, eyes with normal visual fields had a slightly larger mean (+/- standard error of the mean) disc rim area (0.90 +/- 0.04 mm2) than eyes with glaucomatous visual field defects (0.78 +/- 0.05 mm2). However, both sets of eyes in the asymmetric primary open-angle glaucoma patients had smaller mean disc rim areas (P less than 0.0007) than did the control group (1.27 +/- 0.09 mm2). These findings support the hypothesis that loss of the optic disc rim can be detected before perimetric abnormalities develop in primary open-angle glaucoma.

Female↗
PubMed1987

The effect of hCG on cyclic AMP in rabbit ciliary processes.

Experiments designed to address the role of cyclic AMP as a mediator of the eye pressure and aqueous flow reducing effects of human chorionic gonadotropin (hCG) in the rabbit have been conducted. No significant stimulatory effect of hCG on particulate preparations of adenylate cyclase from rabbit ciliary processes could be found under several different experimental conditions. Forskolin, an activator of adenylate cyclase can, in some biological systems, reveal a significant hormonal cyclic AMP response which is undetectable in the presence of hormone alone. Forskolin did potentiate the effect of isoproterenol on cyclic AMP production by intact rabbit ciliary processes. Cyclic AMP production by intact ciliary processes was not affected by hCG, either in the presence or absence of forskolin. Significant specific binding of iodinated hCG to particulate preparations of rabbit ciliary processes could not be detected. These results dispute the role of cyclic AMP as a mediator of the flow and pressure reducing effects of hCG; however, theoretical and methodological complications relating to this interpretation are discussed.

Adenylyl Cyclases↗
PubMed1987

Celiprolol versus timolol and placebo: a two week double-blind comparison.

Celiprolol (5%) was compared to timolol (0.5%) and placebo in patients with primary open angle glaucoma or ocular hypertension. A total of 28 patients participated in this double blind study and received treatment for two weeks. Intraocular pressure decreased an average of 4.4 mmHg with celiprolol and 7.1 mmHg with timolol two hours after instillation. This was maintained 12 hours after administration of timolol but not after celiprolol. There was a small but statistically significant decrease in pulse rate 2 hours after administration of timolol (from 72 to 64 beats per minute) which was not observed after celiprolol. Side effects were mild and similar for all 3 groups.

Adrenergic beta-Antagonists↗
PubMed1987

Chorionic gonadotropin decreases intraocular pressure and aqueous humor flow in rabbit eyes.

The effect of human chorionic gonadotropin (hCG) on the rabbit eye was studied. Intravitreal injections of hCG in albino rabbits provoked a reduction of intraocular pressure (IOP). Intravenous administration of hCG in single doses of 5,000-10,000 units in male pigmented rabbits caused a significant reduction in IOP from 1.5-5 hr after injection. When two successive intravenous doses of 5,000 units of hCG were given at 0 and 3 hr to pigmented rabbits, a significant reduction of net aqueous flow occurred, as measured by scanning fluorophotometry. These results indicate that the decrease in aqueous flow rate in the rabbit eye after administration of hCG can account for the reduction in IOP.

Animals↗
PubMed1986

Regulation of intraocular pressure during cyclocryotherapy for advanced glaucoma.

Five eyes of five patients with advanced glaucoma were treated with cyclocryotherapy. Intraocular pressure was monitored by applanation tonometry during the procedure and for the first 24 hours postoperatively. Two patients underwent a standard form of treatment, and exhibited two components of acute increases in intraocular pressure as a result of the procedure. Intraoperatively, intraocular pressure increased abruptly to 60 to 80 mm Hg during the freezing phase of cyclocryotherapy and decreased to baseline levels during the thaw phase. Postoperatively, intraocular pressure increased to approximately 50 mm Hg, peaking six hours after the procedure. We devised a method of manometric regulation of intraocular pressure to prevent significant increases during cyclocryotherapy and used it in three patients. This group maintained intraocular pressures of approximately 25 mm Hg intraoperatively, and exhibited blunted postoperative increases. Manometric regulation of intraocular pressure during cyclocryotherapy for advanced glaucoma may protect seriously compromised optic nerves from further damage, and may represent a safer method of treatment.

Adolescent↗
PubMed1986

Reproducibility of optic disc measurements with computerized analysis of stereoscopic video images.

Computerized digital image analysis of the optic nerve head was performed using a simultaneous stereoscopic video camera system to provide rapid, quantitative measurements of optic nerve head topography. Determination of the variability of the measurements is required to estimate the magnitude of optic nerve change over time that can be reliably detected. Total variability, operator variability, and interoperator variability were studied. Total variability was assessed by analyzing ten sets of video recordings made in each of seven eyes of seven normal subjects, and in seven eyes of seven patients with glaucoma. The median coefficients of variation for measurements of total variability in glaucoma patients were as follows: vertical disc measurement, 1.4%; horizontal disc measurement, 2.1%; disc area, 1.9%; vertical cup/disc, 3.9%; horizontal cup/disc, 3.3%; disc rim area, 7.5%; and volume, 7.6%. Operator and interoperator variabilities were considerably smaller in magnitude.

Data Display↗