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Biomedical subjects

J Friend

Publications and source records attributed to J Friend.

At least 55 records · Page 3Linked to original sources
PubMed1987

Conjunctival epithelium in healing of corneal epithelial wounds.

The mitotic rate and goblet cell content of conjunctival epithelium following total or central corneal epithelial removal using n-heptanol was measured to determine how the conjunctival epithelium responds to injury and whether conjuctiva responds to central corneal epithelial loss. One day following a wound that removed corneal, limbal, and 1-2 mm of bulbar conjunctival epithelium, the mitotic rate of the remaining conjunctival epithelium was ten times normal (P less than 0.001), proving that the conjunctiva responds to injury by cellular proliferation. At 1 and 2 days following a limited 10 mm diameter central corneal wound, the mitotic rate of peri-limbal conjunctival epithelium was three to four times normal (P less than 0.01), and even following a 5 mm diameter central wound, it was three to four times normal on day 1 (P less than 0.05). Goblet cell frequency was a less reliable indicator of conjunctival response to corneal injury: it was decreased following the largest and smallest wounds but not affected by the 10 mm diameter wound. These studies demonstrate that conjunctival epithelium peripheral to the cornea is affected by small central corneal wounds, and may therefore play a role in corneal epithelium healing.

Animals↗
PubMed1987

Comparison of central and peripheral human corneal epithelium in tissue culture.

Past attempts to grow human corneal epithelium in culture had limited success, with confluence rarely attained. This work is to determine whether different areas of human corneal epithelium grow better in tissue culture. We compared the extent, the mitotic rates, and morphology of outgrowths and histology of explants from central and peripheral human corneas in culture. Explants, 2 mm in diameter, removed from eye bank eyes, were placed epithelial side up on a culture dish with modified SHEM tissue culture medium (Jumblatt et al, 1983). After 7 days, the tissues were fixed, stained and the area of outgrowths from explants measured using an image processor. For eight eyes from donors averaging 66 yr old, the average area of central outgrowths was 7.8 +/- 1.1 mm2, while that of peripheral outgrowths was 52.8 +/- 5.2 mm2 (P less than 0.001). The mitotic rate of outgrowths of central epithelium was significantly less than that of peripheral epithelium (1.1 +/- 0.5% vs 18.8 +/- 0.8%) (P less than 0.001). After 14 days, central outgrowths had not attained confluence and consisted of large cells. Peripheral outgrowths had attained confluence and consisted of small polygonal cells. Histology of explants showed that only one layer of epithelium remained on the stroma in central explants, but several layers were present on the peripheral explants. Thus, peripheral human corneal epithelium grows better in culture than does central human corneal epithelium.

Cornea↗
PubMed1987

In vivo effects of 5-FU on ocular surface epithelium following corneal wounding.

We evaluated the dose relationship between the antiproliferative and toxic effects of 5-fluorouracil (5-FU) on the ocular surface epithelium following experimental corneal epithelial wounding in rabbits. Central corneal epithelial defects 8 mm in diameter were made using n-heptanol. 5-FU (0.05 mg, 0.5 mg, or 5.0 mg per day in divided doses) or saline was applied topically for up to 18 days beginning on the day of wounding. The animals were sacrificed at 1, 7 or 14 days after wound closure. The effect on the ocular surface epithelium was assessed by observation of the clinical and histological appearance, and determination of the rate of corneal epithelial defect closure, corneal epithelial mitotic rate and conjunctival goblet cell frequency. A daily dose of 0.05 mg of topical 5-FU for 18 days had no discernable clinical or histopathological effect compared to wounded, saline treated controls. Treatment with 0.5 mg daily prevented the high mitotic rate typically noted 1 day immediately following defect closure, yet had no significant effect on clinical appearance, histological appearance, or healing rate. Daily topical application of 5.0 mg of 5-FU reduced the corneal epithelial mitotic rate to approximately 1% of the wounded controls, with persistent epithelial defects occurring in 22% of the eyes in this group. In those eyes which did heal, the corneal epithelium was markedly thinner than controls 1 day after defect closure. Fourteen days after healing, epithelial thickness in this group varied from 2 to 13 cells across each cornea, with the thickest area occurring centrally and tapering gradually to the limbus.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1986

On the mechanisms of kappa-opioid-induced diuresis.

In conscious saline loaded rats, the kappa-opioid agonists tifluadom, U50488, and ethylketocyclazocine, given subcutaneously, induced a characteristic diuresis which could be antagonized by naloxone. Bilateral adrenal demedullation significantly reduced adrenal gland catecholamine content and plasma adrenaline levels, but did not significantly affect plasma corticosterone levels, indicating that the adrenal cortex remained both intact and functional. Seven days following bilateral adrenal demedullation, the subcutaneous administration of the kappa-agonists no longer induced diuresis. However, demedullation did not affect the diuretic response to frusemide or clonidine, nor did it affect the antidiuretic response induced by the mu-opioid agonists morphine and buprenorphine. Adrenal catecholamines do not appear to be involved in kappa-opioid-induced diuresis, since pretreatment with propranolol, prazosin and idazoxan did not affect the diuretic response in intact animals. The results indicate a link between the adrenal medulla and kappa-opioid-induced diuresis and suggest that a peripheral mechanism may also be involved in mediating this effect.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1986

Inhibition of vascularization in rabbit corneas by heparin: cortisone pellets.

The purpose of this work was to study the effectiveness of heparin plus cortisone, and of cortisone alone in control of corneal vascularization in rabbit eyes. Corneal vascularization was induced by de-epithelialization of the cornea and limbus and part of the bulbar conjunctiva with concurrent trephination and excision of a central 2-mm diameter corneal button. Inhibition of vascularization by polymer pellets impregnated with heparin (Panheprin, Abbott Laboratories; Chicago, IL) and cortisone, or neither drug was studied by implanting the pellets into the eyes at the time of injury and following the eye clinically and histologically. Wounded corneas with empty pellets developed vascularization extending from the limbus to the central cornea within 3 wk (n = 10). In other wounded eyes, heparin:cortisone pellets prevented vascularization (n = 10) while cortisone pellets slowed, but did not totally inhibit vascularization (n = 6). In other eyes, clear autografts were transplanted into vascularized eyes; and the ability of the drug-impregnated pellets to inhibit grafts vascularization was evaluated. In eyes with heparin:cortisone pellets inserted into the donor button at the time of keratoplasty, the autografts remained clear for at least 6 wk (n = 10) but subsequently vascularized if the sutures were not removed, while cortisone pellets slowed but did not block vascularization (n = 6). If heparin:cortisone pellets were inserted into the vascularized host tissue, rather than into the donor button, vascularization of the graft occurred (n = 6). Thus, heparin (Panheprin, Abbott Laboratories; Chicago IL) plus cortisone inhibited vascularization in rabbit cornea in the models studied: The effect of other commercially available heparins remains to be studied.

Animals↗
PubMed1985

Liposomal immunisation against snake venoms.

A method is described which produces a high, permanent antibody response following a single injection of venom. Animals (mice, rabbits, sheep) were given intravenous, subcutaneous or orally administered Nigerian Echis carinatus (carpet viper) venom which had been incorporated into sphingomyelin-cholesterol liposomes whose membranes had been stabilized by cross-linking adjacent molecules of sphingomyelin using osmium tetroxide. Before use the preparations were thoroughly dialysed to remove any unbound osmium tetroxide. Antibody levels were estimated using enzyme immunoassay. Venom treated in this way and administered i.v. or s.c. produced a powerful, sustained and protective antibody response lasting for the lifetime of a mouse. We also report the development of significant antibody responses after oral administration of liposome-entrapped but not free venom.

Animals↗
PubMed1985

Transplant of corneal epithelium to rabbit corneal wounds in vivo.

Sheets of corneal epithelium removed from 9-mm buttons of adult rabbit corneas using Dispase II were placed on abraded (basement membrane intact) or keratectomized corneas of anesthetized rabbits. Both types of wounds extended from limbus to limbus. The host animals were maintained under deep anesthesia for 3 hr, during which time culture medium was dripped onto the surface of the transplant. A soft contact lens then was placed over the cornea and the eye bandaged shut. Short-term experiments indicated that after 24 hr the transplanted epithelium was adherent to both abraded and keratectomized corneas (n = 4). Hemidesmosomes had formed between basal cells of donor epithelium and denuded host basement membrane, and cytoplasmic blebs had extended from donor epithelium into host keratectomized stroma. Seven transplants to abraded corneas and 17 transplants to keratectomized corneas were followed for longer time periods. Six of the seven transplants to abraded corneas were maintained until termination of the experiment (four at 4 weeks, one at 2 weeks, one at 1 week). Three of the 17 transplants to keratectomized corneas were maintained until termination (one at 4 weeks, one at 2 weeks, and one at 6 days). The remaining 14 sloughed between days 2 and 6. These data indicate that it is feasible to transplant corneal epithelial sheets and that they can be maintained most successfully if the host basement membrane is present.

Animals↗
PubMed1985

Collagen gel for ocular surface.

A replacement ocular surface requires a substrate that is easily manipulated surgically, does not cause an inflammatory reaction, and is nontoxic to epithelial cells. This work evaluates the usefulness of a collagen gel as a substrate for corneal epithelial cells by determining the ocular toxicity of the gel and the ability of the gel to support and maintain corneal epithelial cells in vitro. Collagen gels, made from Vitrogen, were easily manipulated and were well-tolerated in rabbit eyes for up to 6 wk (n = 3). Epithelial sheets placed on collagen gels and incubated at 37 degrees C for up to 13 days remained well-apposed to the gels and appeared normal, but thinned, from five to three layers. The basal cells extended cytoplasmic blebs into the gels, but only one sheet of five sheets showed basement membrane deposition by 6-13 days. Thus, the collagen gels appear to meet the criteria defined above and may be a suitable substrate in biofabricated ocular surfaces.

Animals↗
PubMed1985

Corneal epithelial dysplasia.

Corneal epithelial dysplasia is a rare clinical problem. It is not known whether the corneal epithelial cells undergo dysplastic changes in situ or in the region of the limbal or conjunctival epithelium with subsequent centripetal migration onto the cornea. We obtained an intact, dysplastic corneal epithelial sheet and samples of conjunctival tissue from a 75-year-old patient. Light and transmission electron microscopic examination of the dysplastic corneal epithelium showed histologic evidence of conjunctival, limbal, and corneal epithelium. The adjacent conjunctiva appeared normal except for a possible slight decrease in goblet cells. The 3H-thymidine uptake indicated a normal mitotic index for the conjunctiva. Glycogen content of the dysplastic sheet showed high values seen with corneal and not conjunctival epithelium. The dysplasia recurred despite wide conjunctival resection. Although no final conclusions can be made, we feel our studies support the hypothesis that the dysplastic process in our patient arose de novo in the corneal epithelium.

Aged↗
PubMed1985

5-Fluorouracil toxicity to the ocular surface epithelium.

The antimetabolite, 5-fluorouracil (5-FU), has been used to control proliferation of retinal pigment epithelial cells and fibrocytes, and is currently the subject of a multicenter clinical trial of its value in the control of scarring after glaucoma operations. To evaluate possible ocular surface toxicity, the effect of 5-FU on the mitotic rate and differentiation of the ocular surface epithelium in rabbits was measured. 5-FU was instilled into eyes with 10-mm diameter central epithelial wounds and into nonwounded eyes at a dose of 9 mg per day for 4 days. Saline treated control wounded eyes healed within 4 days (n = 5) while 40% (4 of 10) of the 5-FU treated wounded eyes had defects at 4 days. The normal mitotic rate of the corneal epithelium was 1.0 +/- 0.3 (n = 4) tritiated thymidine labeled cells per 100 basal corneal epithelial cells after 2.5 hr incubation. Saline treated control wounded eyes had an increased mitotic rate, 7.1 +/- 1.3 (n = 5) labeled cells per 100 basal corneal epithelial cells after 2.5 hr incubation. Topical 5-FU decreased both of those rates to about 1% of normal. The normal conjunctival epithelial mitotic rate was 1.8 +/- 0.4 (n = 4) labeled cells per 60 basal cells after per 2.5 hr incubation. This rate was the same in wounded eyes, but was decreased in eyes treated with 5-FU. Thus, 5-FU (9 mg/day topically) has serious toxic effects to ocular surface epithelium which must be carefully considered if this drug is to be used clinically.

Animals↗
PubMed1984

Ocular cicatricial pemphigoid associated with hyperproliferation of the conjunctival epithelium.

We determined the mitotic rate, measured by evaluating uptake of tritiated thymidine autoradiographically, and the frequency of goblet cells in conjunctival epithelial biopsy specimens from nine normal subjects and from 11 patients (seven women and four men ranging in age from 50 to 80 years) with ocular cicatricial pemphigoid. The mitotic rate of patients with the disease was significantly higher than that of normal subjects, 7.2 +/- 2.2 vs 1.6 +/- 0.2 labeled cells per 100 basal epithelial cells (P less than .01). The goblet cell frequency, however, was significantly less in patients than in normal subjects. This suggests that ocular cicatricial pemphigoid is associated with hyperproliferation of the conjunctival epithelium, with a concurrent failure of normal conjunctival differentiation.

Aged↗
PubMed1984

Histology of human conjunctival transplantation.

The technique of conjunctival transplantation has proven very successful in reestablishing an intact ocular surface in patients with severe ocular surface disease in whom conventional treatment has failed. We present follow-up on the histology of the transplanted conjunctival tissue in four alkali-burned patients who underwent penetrating keratoplasty 3-28 months following conjunctival transplantation. The corneal button was re-epithelialized in all patients. The fate of the transplanted tissue agreed with experimental observations made in the rabbit model, i.e., under areas of vascularization and inflammation, the transplanted tissue resembled conjunctiva with numerous goblet cells and 3-4 cell layers of nonkeratinized, stratified epithelium. In one patient, a definite "transition zone" from conjunctival to corneal appearing epithelium was seen in an area with minimal inflammation and vascularization, again confirming the animal results showing that transdifferentiation of conjunctival to corneal epithelium can occur.

Adult↗
PubMed1984

Conjunctival epithelial wound healing.

In vivo conjunctival epithelial healing in albino rabbits was investigated by light microscopy following both n-heptanol and trephined conjunctival wounding. Reepithelialization occurred faster following n-heptanol treatment (3 days) versus trephination (6-7 days). No goblet cells were present in the migrating epithelium during reepithelialization. After 1 day of wounding, goblet cells disappeared several millimeters peripheral to the wound margin in both types of wounds. Goblet cells first reappeared peripherally 1 week after wounding before they appeared in the central wound area. These observations indicate that a large area of conjunctival epithelium surrounding a wound is involved with repair of that wound. Since the goblet cell content of conjunctival epithelium appears to change as a result of the stresses of epithelial repair, the goblet cell population may reflect the presence of reparative or proliferative processes in the ocular surface.

Animals↗