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Biomedical subjects

J R Samples

Publications and source records attributed to J R Samples.

At least 37 records · Page 2Linked to original sources
PubMed1993

Ocular inflammatory effects of intravitreally injected interleukin-2.

The primary, known physiologic effect of interleukin-2 (IL-2) is to act as a T lymphocyte growth factor. We investigated the potential contribution of IL-2 to intraocular inflammation by studying the inflammation resulting from the intravitreal injection of recombinant, human IL-2 in New Zealand white rabbits. Serial slit lamp observations indicated that 40 microgram of intravitreally injected IL-2 induced an anterior uveitis which was maximal 5 days after the injection. Inflammation was less marked but still significant with amounts of IL-2 as low as 400 ng. Direct examination of aqueous humor confirmed elevations of protein, prostaglandin E2, and mononuclear cells which correlated with the clinical observations. The kinetics of the response to intravitreal IL-2 distinguished it from the responses to other intravitreally injected cytokines such as interleukins 1, 6, or 8 as well as tumor necrosis factor. Intramuscular injection of cyclosporine A significantly reduced the protein extravasation associated with IL-2 injection, but cyclosporine had no effect on inflammation secondary to an intravitreal injection of interleukin-1. These observations implicate IL-2 as a potential contributor to uveitis. In addition, the studies with cyclosporine indicate the heterogeneity of inflammation such that pharmacologic agents which affect one cause of uveitis are not necessarily efficacious in another model.

Animals↗
PubMed1993

Regulation of the levels of human trabecular matrix metalloproteinases and inhibitor by interleukin-1 and dexamethasone.

PURPOSE: The regulation of the trabecular meshwork's extracellular matrix is poorly understood and may involve a family of secreted proteinases, the matrix metalloproteinases. Because the trabecular extracellular matrix has been hypothesized to affect intraocular pressure, an evaluation was made of the ability of two cellular modulators to change the levels of matrix metalloproteinases in the medium of human trabecular meshwork organ explant cultures. METHODS: Trabecular explant cultures were exposed to recombinant human interleukin-1 alpha, dexamethasone, or combinations thereof for 72 hours and the culture medium was collected for analysis. Levels of stromelysin, the 72 kD gelatinase A and the 92 kD gelatinase B enzyme activity in this culture medium were assayed by substrate gel electrophoresis (zymography). Stromelysin and the tissue inhibitor of metalloproteinases (TIMP1) media protein levels were analyzed using immunoblots of Western transfers. RESULTS: Culture medium of unstimulated explants contains significant levels of the 72 kD gelatinase A and only low levels of the 92 kD gelatinase B, stromelysin, and TIMP1. Interleukin-1 alpha produces a dose-dependent several-fold elevation of gelatinase B, stromelysin, and TIMP1 without changing gelatinase A levels. Dexamethasone produces no significant change in gelatinase A and only small increases in stromelysin, gelatinase B, and TIMP1. When added together, dexamethasone antagonizes the interleukin-1 alpha-induced increase of stromelysin, gelatinase B, and TIMP1 in a dose-dependent manner. CONCLUSION: These modulators may be useful in analyzing the roles of this enzyme family in normal trabecular homeostasis and perhaps in the etiology of glaucoma.

Aged↗
PubMed1991

Synthesis of platelet activating factor by ocular tissue from inflamed eyes.

Platelet activating factors (PAFs) are a family of ether lipids with properties that suggest a major role in inflammation. We have previously implicated PAFs in ocular inflammation based on the inhibition of several rabbit models of iritis with a specific PAF receptor antagonist. We have tested ocular tissues for the ability to synthesize PAF. Iris, ciliary body, cornea, and/or retina were carefully dissected from New Zealand white rabbits, and tissue from four eyes was pooled. Tissues were stimulated with calcium ionophore (10 mumol/L), and supernatants were extracted with chloroform-methanol. Platelet-aggregating activity was found in the chloroform phase in 2 of 9, 1 of 8, 0 of 9, and 3 of 9 studies involving iris, retina, ciliary body, or cornea, respectively. Twenty-four hours after the intravitreal injection of 125 ng of endotoxin, aggregating activity was consistently detectable from supernatants of stimulated iris and ciliary body, occasionally present from stimulated retina but not detectable from cornea. The shape of the aggregation curve resembled that produced by 0.5 to 2.0 ng of authentic PAF. Moreover, the aggregation could be completely inhibited by a PAF receptor antagonist and the aggregating activity chromatographed identically on high-performance liquid chromatography to a PAF standard. These studies indicate that PAF-like activity could be detected from several ocular tissues subsequent to inflammation. Iris, ciliary body, retina, vascular endothelium, and/or leukocytes could each contribute to the presence of this inflammatory mediator.

Animals↗
PubMed1991

Propagation of human corneal endothelium in vitro effect of growth factors.

Endothelial cells were obtained from 23 human corneal-scleral rims. Donors were 0.2-37 yr of age. Most cultures obtained from donors under 30 yr ceased to grow after the seventh passage (3-24 weeks). Growth from 17- and 25-yr-old donors were maintained for nine passages (26 weeks) and 18 passages (100 weeks), respectively. Cultures were established from 12 rims, using growth factors in uncoated culture flasks or epidermal growth factor (EGF) in an extracellular matrix-coated (ECM) flask. EGF improved the growth potential of the cells; a combination of an ECM-coated-tissue culture flask with EGF in the medium provided an improved environment for continuous growth.

Adolescent↗
PubMed1991

Expression of matrix metalloproteinases and inhibitor by human trabecular meshwork.

Extracellular matrix (ECM) turnover and remodeling are initiated, at least in part, by the regulated secretion of members of a family of matrix metalloproteinases. Human and bovine trabecular mesh-work in culture secrete interstitial collagenase, both the 72- and the 92-kD forms of type IV collagenase (gelatinases) and stromelysin, and the tissue inhibitor of metalloproteinases (TIMP). These proteinases and TIMP were identified by immunoblotting western transfers from sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) using several specific antiprotein and antipeptide polyclonal antibodies. Gelatinase and stromelysin enzymatic activities were also analyzed by substrate SDS-PAGE, in which proteinase substrates were polymerized into the gels before electrophoresis to allow subsequent activity assays. These matrix metalloproteinases and TIMP are secreted at low basal levels into trabecular culture medium; their secretion levels are increased several-fold by treatment of the cultures with the phorbol mitogen. 12-O-tetradecanoylphorbol-13-acetate (TPA). Characteristics of the trabecular matrix metalloproteinases and TIMP are similar to those secreted by numerous other tissues, including the retinal pigment epithelium. These proteinases may serve an important role in the maintenance and regulation of the trabecular extracellular matrix and, subsequently, of the aqueous humor outflow pathway in normal and glaucomatous eyes.

Animals↗
PubMed1989

Trabecular repopulation by anterior trabecular meshwork cells after laser trabeculoplasty.

To study further the transient increase in trabecular cell division within the first two days after laser trabeculoplasty in human corneoscleral explant organ cultures, we used a pulse-chase protocol in which immediately after laser treatment 3H-thymidine was added to the culture medium for 48 hours (the pulse period). Fresh medium without radiolabel was then added for variable times (the chase period) before termination of the experiment. Autoradiography was used to follow changes in the regional distribution of the cells that divided during the pulse period and had 3H-thymidine-labeled DNA. Laser-treated explants, evaluated after a pulse with no chase, showed a fourfold increase in cell division (P less than .001) over nontreated controls. Nearly 60% of this cell division was localized to the anterior, nonfiltering region of the trabecular meshwork where it inserts into the cornea beneath Schwalbe's line. Trabecular cell division in other regions of the meshwork was not increased over controls at this time. After seven or 14 days of chase without radiolabel, the regional distribution of radiolabeled cells changed in laser-treated explants but not in controls. By 14 days, only 26% of the labeled cells remained in this anterior insert region, while 60% were found in the region of the burn sites. Macroautoradiography of whole explants corroborated these observations. Our data support the hypothesis that laser trabeculoplasty causes early cell division by a population of cells in the anterior meshwork; these new cells then migrate and repopulate the burn sites over the next few weeks.

Humans↗
PubMed1989

The effect of epinephrine and benzalkonium chloride on cultured corneal endothelial and trabecular meshwork cells.

We evaluated the effect of dipivefrin hydrochloride, epinephrine hydrochloride, epinephrine borate and their respective vehicles with and without the preservative benzalkonium chloride, on the in vitro growth characteristics of human corneal keratocytes, endothelial cells and trabecular meshwork. Epinephrine hydrochloride and borate at low concentrations (0.0002%) significantly inhibited growth of both trabecular meshwork and corneal endothelial cells. Higher concentrations (0.02%) of these same drugs induced the same effect on the growth of keratocytes in vitro. Similar observations were made on the effect of dipivefrin hydrochloride on human corneal cells in vitro. Benzalkonium chloride alone was demonstrated to be responsible for the growth inhibitory effects on trabecular cells. The susceptibility of trabecular meshwork cells in culture to the commonly used ophthalmic preservative benzalkonium chloride is demonstrated.

Benzalkonium Compounds↗
PubMed1989

Dolichoectasia and cranial nerve palsies. A case report.

An elderly man with glaucoma and acute onset of left-sided cranial nerve III, V, and VII palsies was found to have associated marked intracranial artery dolichoectasia. Dolichoectasia (arterial elongation and distension) affects the intracranial arteries, producing various neurological and ophthalmological findings. The patients are usually men who are more than 40 years old and have a history of hypertension. Diagnosis is made by characteristic radiologic findings. In patients with neurologic symptoms and signs suggesting a space-occupying mass, intracranial dolichoectasia should be considered.

Aged↗
PubMed1988

The effect of repeat argon laser trabeculoplasty.

A select population of patients received repeat laser trabeculoplasties of 40 to 100 burns over 180 to 360 degrees. These eyes had shown an excellent prolonged response to initial laser trabeculoplasty. Eight of 11 eyes with greater than one year follow-up showed a sustained hypotensive response to repeat laser trabeculoplasty. No significant posttreatment intraocular pressure increases were observed. Repeat argon laser trabeculoplasty was effective for these patients who had shown a prolonged response to their initial treatment.

Argon↗
PubMed1988

Trabecular cell division after argon laser trabeculoplasty.

The usefulness of argon laser trabeculoplasty (ALT) in the treatment of some patients with glaucoma has been established; yet, the mechanism of ALT is not understood. The hypothesis that the mechanism involves trabecular cell division was examined. Autoradiographic assessment of tritiated thymidine incorporation into trabecular cell DNA in a human corneoscleral explant organ culture system demonstrated a basal level of DNA replication that increased by 180% in the two days immediately after ALT. When labeling was initiated five days after ALT, DNA replication declined to 70% of the control level. The autoradiographic findings were confirmed using biochemical evaluation of tritiated thymidine incorporation into acid-precipitable macromolecules (DNA) in excised trabecular meshwork. One biologic response of the trabecular meshwork after laser trabeculoplasty is a change in the level of ongoing trabecular cell division.

Argon↗
PubMed1988

Prostaglandin-independent inhibition of ocular vascular permeability by a platelet-activating factor antagonist.

Platelet-activating factor (PAF), a lipid mediator of inflammation, may markedly increase vascular permeability. We assessed the ability of the PAF antagonist SRI 63-441 to inhibit ocular vascular permeability induced by the intravenous injection of endotoxin or anterior chamber paracentesis. The PAF antagonist SRI 63-441 significantly blocked ocular vascular permeability following either intravenous endotoxin or anterior chamber paracentesis as determined by the reduction in accumulation of 70,000-molecular-weight fluorescein isothiocyanate-conjugated dextran or serum proteins into the anterior chamber. SRI 63-441 did not reduce increases in aqueous humor prostaglandin E2 levels. The efficacy of the PAF antagonist was additive in combination with either topical indomethacin or topical corticosteroid. Combined therapy almost completely prevented increases in ocular vascular permeability. These data support the conclusion that multiple mediators contribute to ocular vascular permeability and that combinations of pharmacologic agents may be superior to a single drug.

Animals↗
PubMed1988

Effect of melatonin on intraocular pressure.

We studied the effect of orally administered melatonin on intraocular pressure in humans. We suppressed serum melatonin levels by exposing our subjects to bright light. Our experiments suggest that melatonin lowers intraocular pressure in man. This may prove to be a therapeutically useful agent since melatonin appears to be relatively free of side effects and is effective in small quantities.

Administration, Oral↗
PubMed1988

Ocular inflammatory effects of intravitreally-injected tumor necrosis factor.

Many of the pathophysiologic effects of bacterial endotoxin have recently been attributed to a monokine, tumor necrosis factor (TNF). The rabbit eye is extremely sensitive to locally injected endotoxin. The authors have investigated the possible contribution of TNF to ocular inflammation in a rabbit model. The intravitreal injection of 10(5) to 5 X 10(5) units of recombinant human TNF produced a sustained disruption of the blood-aqueous barrier as manifested by elevated aqueous humor protein levels. In addition, 83% of rabbits receiving this dose of TNF developed hyperemia of limbal vessels and early neovascularization of the cornea. Many developed posterior synechiae (fibrous adhesions between the iris and the lens). TNF induced only a slight cellular response in the anterior chamber. Histologic studies confirmed the presence of new vessels and demonstrated a marked mononuclear infiltrate within and beneath the epithelium of the iris and ciliary body. Lower doses of TNF produced inconsistent results. Heating TNF completely destroyed its inflammatory effects. The time course of the ocular response to TNF and the quantity of recombinant protein needed to produce consistent effects were vastly different from effects observed with interleukin-1. For example, 24 hours after an intravitreal injection, 2.2 X 10(4) ng of TNF (5 X 10(5) units) produced significantly less protein extravasation and polymorphonuclear leukocyte infiltration than 4 ng of recombinant interleukin-1. Similarly, 24 hours after intravitreal injection, 1 ng of Escherichia coli endotoxin tended to be a more potent inflammatory stimulus than this quantity of TNF. These observations indicate that the ocular pathophysiologic effects of TNF can be readily distinguished from changes induced by either endotoxin or another endotoxin induced monokine, interleukin-1.

Animals↗
PubMed1988

Human trabecular meshwork organ culture: morphology and glycosaminoglycan synthesis.

Human corneoscleral explants were maintained for several weeks in defined, serum-free media. Trabecular cell vitality, as judged by vital stain exclusion, is high for at least one month. Trabecular ultrastructure, as compared to that of fresh eyes, first shows minor cellular and extracellular matrix degradation after 3 weeks in culture. The biosynthetic profiles of trabecular glycosaminoglycans (GAGs) change significantly by 3 weeks in culture. Eyes that are stored at 5 degrees C for up to 48 hr postmortem exhibit changes in trabecular ultrastructure and in GAG profiles; both characteristics return to normal by 7 days in culture. The incorporation pattern of 35S-sulfate and 3H-glucosamine into the GAGs of the trabecular meshwork (TM) is distinct from corneal or scleral incorporation. The relative incorporation of 3H-glucosamine into trabecular GAGs, as determined by sequential enzymatic degradation, is: 22.3% hyaluronic acid (HA), 27.9% chondroitin sulfate (CS), 21.3% dermatan sulfate (DS), 5.9% keratan sulfate (KS), 17.7% heparan sulfate (HS) and 4.9% unidentified material. The relative incorporation of 35S-sulfate into trabecular GAGs is: 0% HA, 32.9% CS, 34.8% DS, 7.7% KS, 13.8% HS and 11.1% into unidentified material. This profile is in good agreement with the profile that was previously obtained for human and nonhuman primate meshworks prior to culture. We conclude that corneoscleral explant organ culture is a useful tool for extracellular matrix studies within a time window from 7 to at least 14 days in culture.

Aged↗
PubMed1988

A technique for removal of filariasis of the anterior chamber.

We describe a useful technique for removing filaria from the anterior chamber. In the case described, an immature female filaria approximately 15 mm in length was removed from the anterior chamber of a 32-year-old man in western Oregon and identified as a species of Dipetalonema. Features of four cases of filarial infection in the anterior chamber from the same geographic area are described. In three out of four cases, the worms were removed alive without difficulty by means of simple irrigation aspiration system.

Adult↗