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Biomedical subjects

B M Gebhardt

Publications and source records attributed to B M Gebhardt.

At least 73 records · Page 4Linked to original sources
PubMed1988

HSV-specific IgA from tears blocks virus attachment to the cell membrane.

The results of this investigation demonstrate that the IgA antibody in tears inhibits the attachment of herpes simplex virus (HSV) to cells and implicate immunoglobulin A (IgA) isotype antibody in the protection of the ocular surface. Tears were collected from the eyes of infected and uninfected rabbits and tested for the presence of infectious virus, for viral neutralization titer, and in an enzyme-linked immunoassay (ELISA) for antibody to HSV. Neither the tears from the uninfected rabbits nor the tears from the infected rabbits produced viral cytopathic effects on indicator cells in vitro. Tears from uninfected rabbits had no virus neutralization capacity while the tears from infected rabbits had titers of 1:10 to 1:40. Tears collected from HSV-1 infected rabbits, but not uninfected rabbits, had anti-HSV antibody titers as determined by the enzyme-linked immunosorbent assay. Lectin affinity column enrichment of IgA from the tears of uninfected and infected rabbits was examined for the capacity to block viral adsorption to cells using 32P-labeled virus. It was found that exposure of the radio-actively-labeled virus to the purified IgA fraction of tears from infected rabbits reduced the amount of virus binding to Vero cells, whereas the purified IgA obtained from uninfected tears had minimal activity. These results may imply a role for the IgA-containing fraction of tears from HSV-infected animals in preventing viral attachment to cells and suggest that antibody of this isotype plays a protective role at the ocular surface.

Animals↗
PubMed1988

The effect of tissue dose and site of grafting on immunity to corneal allografts.

The purpose of this investigation was to determine the quantitative relationship between corneal alloantigens and host immunity. In addition, the effect of the site of introduction of the corneal antigens on the host response was determined. Two alloantigenic strains of rats were reciprocally grafted at three different locations in the body with carefully quantitated amounts of corneal tissue: (1) orthotopically in the cornea of the eye; (2) subcutaneously; and (3) intraperitoneally. Corneal tissue placed orthotopically into vascularized graft beds did not elicit a systemic immune response. Subcutaneous grafts elicited a weak systemic alloantigenic response, whereas corneal tissue placed in the peritoneal cavity consistently induced a vigorous cellular and humoral alloantigenic response. Eight or more full thickness corneal allografts grafted subcutaneously were required to elicit a systemic response. On the other hand, as few as four corneal allografts placed intraperitoneally invariably elicited a systemic alloimmune response. The results of this investigation demonstrate that both the amount and route of introduction of alloantigen affect the recipient's response to corneal tissue and that the rejection of a single orthotopic cornea graft is a site-limited response. Immune effector cells were not found in the spleens and alloantibodies were not present in the serum of animals that had rejected corneal allografts.

Animals↗
PubMed1988

T lymphocytes in the trigeminal ganglia of rabbits during corneal HSV infection.

The results of this investigation reveal, for the first time, the presence of thymus-derived (T) lymphocytes in the trigeminal ganglia of rabbits undergoing primary corneal infection with herpes simplex virus type 1. Infiltration of T cells into the trigeminal ganglion was evident at 15 days after primary ocular infection but these cells were no longer present by 45 days after infection. Corneas and trigeminal ganglia of rabbits sacrificed at 3, 7, 12, 15, 20, 25, 30, 45, 70 and 90 days after infection were assayed for infectious virus and stained for viral antigen and immunoreactive T cells. Infectious virus and cells expressing viral antigens were present in the corneas and trigeminal ganglia during the acute phase (day 0-day 14) of the infection. T cell infiltration of the trigeminal ganglion was present as a perivascular infiltrate along with a sparse scattering of these cells among the nerve fibers. The perivascular infiltration is characteristic of viral infection of a tissue and was not seen in the sections of trigeminal ganglia obtained earlier than 15 days or in ganglia obtained 45 days or more after primary corneal infection. This investigation demonstrates conclusively that the neural ganglia are not completely shielded from the host immune response, as evidenced by the observation that immunocompetent T lymphocytes infiltrate the ganglia subsequent to the infection of a peripheral tissue such as the cornea of the eye.

Animals↗
PubMed1988

Topically applied cyclosporine in azone prolongs corneal allograft survival.

The purpose of this study was to develop and test a topical ocular delivery system for the immunosuppressive drug cyclosporine. To this end, cyclosporine was dissolved in the penetration enhancer, Azone, and applied topically to allografted rabbit eyes. The concentration of cyclosporine in the cornea, the aqueous humor, and blood of the treated rabbits was determined by radioimmunoassay. The effect of the cyclosporine-Azone preparation on the survival of corneal allografts was assessed by clinical evaluation of the grafts and by histopathologic and immunohistologic evaluation of the cellular infiltrate in the grafts. Clinically significant concentrations of cyclosporine were measured in the treated corneas but little or no drug was found in the aqueous humor or blood of the treated animals. Cyclosporine in Azone resulted in suppression in the severity and incidence of graft rejection. The suppression of graft rejection was borne out by the immunohistologic observations. Cyclosporine-treated grafts contained significantly fewer infiltrating T lymphocytes than did the drug/solvent-treated allografts, indicating that the topical application of cyclosporine actively inhibited the entry of T cells into the grafts. This study, for the first time, presents a solvent that is apparently not toxic but is effective in delivering immunologically active concentrations of cyclosporine following topical application to the cornea.

Administration, Topical↗
PubMed1987

The suppression of acute corneal inflammation by Bredinin.

This study tested the effect of Bredinin, a nucleoside antibiotic of fungal origin, on experimentally induced acute inflammation of the rabbit cornea. Inflammation was produced by abrasive removal of a 9 mm disk of corneal epithelium. In the dose-response experiments, one eye of each rabbit was treated topically with Bredinin, and the other eye with vehicle immediately after deepithelialization. The acute inflammatory leukocytes in tear film samples were counted at various times and the corneas were examined histologically at the end of the study. A paired t-test revealed that the numbers of acute inflammatory leukocytes after 5 hours were significantly less in the Bredinin-treated eyes, compared with the untreated eyes. The timing of drug-treatment was important; Bredinin was most effective in suppressing acute ocular inflammation when administered at, or within, one hour of the inflammatory stimulus. Histologic analysis demonstrated fewer acute inflammatory leukocytes on the ocular surface and in the stroma of the Bredinin-treated eyes, compared with the untreated eyes. No obvious corneal toxicity was noted, and the drug-treated eyes appeared less inflamed than the control eyes. The results of this study demonstrate the capacity of Bredinin to suppress the entry of inflammatory leukocytes into the tear film and suggest that this drug may have potential for use as a topical anti-inflammatory agent.

Acute Disease↗
PubMed1987

Fate of lyophilized xenogeneic corneal lenticules in intrastromal implantation and epikeratophakia.

The antigenicity of intrastromal and epikeratophakia xenografts of lyophilized corneal tissue was evaluated in nonimmune and immune recipients. Lyophilized feline lenticules were implanted into intrastromal pockets in unsensitized rabbits and rabbits sensitized to the donor cat. In both cases, the grafts remained clear. Sensitized rabbits with clear intrastromal grafts received fresh tissue penetrating keratoplasty grafts from the same donor cat, placed adjacent to the intrastromal grafts. The fresh tissue penetrating keratoplasty grafts were rapidly rejected, while the lyophilized intrastromal grafts remained clear. Cats sensitized to rabbits received lyophilized and rehydrated epikeratophakia grafts shaped from rabbit cornea; these lyophilized grafts also remained clear for the 3-month period of the study. The results indicate that lyophilized and rehydrated corneal stroma, which is devoid of living cells, is not antigenic and is not subjected to immunologic attack, even in cases where the donor and host are of different species and the host has been previously immunized to the donor.

Animals↗
PubMed1986

Somatomedin production and response to mitogen by lymphocytes in children with growth hormone deficiency.

Studies on the lymphocyte proliferative activity of the sera from growth hormone (GH) deficient patients have resulted in contradictory observations. The ability of lymphocytes to synthesize somatomedin-C (Sm-C) and thus account for a normal proliferative activity (previously observed by us) of the GH-deficient sera was studied, by measuring Sm-C concentration in the culture medium using a standard radioimmunoassay for Sm-C. The response of lymphocytes to the mitogen phytohemagglutinin (PHA), as determined by the incorporation of 3H thymidine into DNA, was also studied. The Sm-C concentrations in the cultures reflected the Sm-C concentrations of the respective serum added and did not alter with significant increases in the cell number induced by PHA. The lymphocytes from GH-deficient children and normal children were indistinguishable in their ability to respond to PHA. We conclude that lymphocyte proliferation in short-term culture, was not associated with an increase in Sm-C and that in the lymphocyte proliferation assay the sera and the lymphocytes from GH-deficient children respond similarly to the sera and lymphocytes from normal children.

Adolescent↗
PubMed1985

Penetration of topical cyclosporine into the rabbit cornea, aqueous humor, and serum.

Systemic and ocular absorption of topically applied 10% cyclosporine ointment was determined in rabbit cornea, aqueous humor, and serum by radioimmunoassay. The concentration of the drug in the cornea reached a peak of 900 ng/mL three hours after application. Substantial levels were still present at 24 hours. Relatively low concentrations were measured in the aqueous humor and serum, suggesting corneal stromal pooling of this hydrophobic cyclic peptide. Topical ocular application of cyclosporine may reduce or eliminate the drug's systemic toxic effects while maintaining a therapeutic level of local immunosuppressive activity.

Absorption↗
PubMed1984

Herpesvirus infection of cornea allografts.

This report describes three patients who have in common an occurrence of ocular epithelial herpes infection following a penetrating keratoplasty for a corneal opacity unrelated to herpesvirus infection. It may be that patients undergoing episodes of graft rejection are at increased risk for the reactivation of herpesvirus latent in the trigeminal ganglia, and corticosteroids should be used with this in mind. Because virtually all adults have been exposed to herpes and therefore harbor latent virus, a viral etiology should be considered for lesions in post-penetrating keratoplasty patients. Although the occurrence of this possibly rejection-related reactivation of herpes simplex virus is undoubtedly rare, management of potential cases of this nature should take this possibility into account.

Adult↗
PubMed1981

Suppression of corneal allograft rejection by cyclosporin A.

Corneal allografts can elicit a host immune response that results in their destruction as functional tissues. Just as with other types of tissue allografts, effective, safe methods are needed to prevent corneal allograft rejection in patients undergoing penetrating keratoplasty. In this study, cyclosporin A, a compound of fungal origin, was tested for its capacity to suppress corneal allograft rejection in rabbits. Corneal allografts were exchanged between pairs of randomly bred albino rabbits. Some animals received retrobulbar injections and others received similar injections of the drug vehicle only. Cyclosporin A significantly prolonged corneal allograft survival. All the allografts in untreated eyes were rejected within 40 days; four (45%) of the nine allografts in treated eyes survived more than 70 days. Cyclosporin A alone was less effective in suppressing allograft rejection in heavily vascularized, inflamed graft sites. No adverse side effects were seen when it was injected locally into the rabbit eye. We conclude that in the acute graft model in this study, cyclosporin A is a safe, potent immunosuppressive agent.

Animals↗
PubMed1981

Blood group antigens on human corneal cells demonstrated by immunoperoxidase staining.

The ultrasensitive immunoperoxidase staining technique demonstrated the presence of blood groups A, B, and D antigens on human corneal epithelial and endothelial cells. Nonspecific staining was not seen and there was little antigen in the corneal stroma. Blood group antigens probably do not initiate corneal allograft rejection, but they may lend antigenic support to the rejection response one it has begun.

Antigens, Surface↗
PubMed1976

Immunologic protection of rabbit corneal allografts with heterologous 'blocking' antibody. Immunologic protection of corneal allografts.

Exchange penetrating keratoplasties were performed in NZW rabbits using conreas soaked in heterologous 'blocking' antibody (guinea pig anti-rabbit gamma-globulin) under various experimental situations and immunogenic stimuli. Results suggest that the antibody can protect the rabbit graft from weak rejection stimuli possibly by blocking the afferent arc of the immunologic reflex, but cannot protect the graft from presensitization, or nonocular sensitization. The use of a blocking antibody in human transplantation would be simple and of slight risk to a graft recipient.

Animals↗
PubMed1976

The effect of splenectomy on corneal graft rejection.

Recent studies have suggested that the spleen may be essential for the "immunologic privilege" enjoyed by corneal grafts. We tested this hypothesis in rabbits by performing 38 exchange penetrating keratoplasties between 19 normal rabbits and 19 rabbits that had undergone splenectomy. No significant difference was found in the number of corneas rejected or the mean graft survival time between the normal and splenectomized rabbits.

Animals↗
PubMed1975

Immunologic protection of rabbit corneal allografts with heterologous blocking antibody.

We performed exchange penetrating keratoplasties in New Zealand White rabbits by using corneas soaked in heterologous "blocking" antibody (guinea pig antirabbit lymphocyte globulin) under various experimental situations and immunogenic stimuli. Results suggested that the antibody can protect the corneal graft from a weak rejection response possibility by blocking the afferent are of the immunologic rejection reflex, but cannot protect a graft subject to a strong immunologic rejection episode. Based on these results, the use of a blocking antibody in human transplantation would be of potential benefit and offer little risk to a graft recipient.

Animals↗