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Biomedical subjects

I Gery

Publications and source records attributed to I Gery.

At least 145 records · Page 8Linked to original sources
PubMed1983

Cyclosporin A: alterations of the cellular immune response in S-antigen-induced experimental autoimmune uveitis.

We have previously shown that Cyclosporin A (CsA) is effective in preventing S-antigen (S-Ag)-induced experimental autoimmune uveitis (EAU). Lewis rats, which readily develop EAU, were studied for the alterations in cell-mediated immune functions associated with CsA therapy. Lymph nodes draining the site of S-Ag immunization were significantly smaller in the CsA-treated animals when compared to the nonprotected group (p less than 0.01), and also showed profound histologic alterations when compared to controls. In vitro responses of lymphocytes from lymph node and peripheral blood were greatly diminished in the CsA-treated animals. Sera from rats treated with CsA also were capable of inhibiting in vitro proliferative responses. These findings demonstrate that CsA-treated Lewis rats have alterations in several cell-mediated immune functions, thereby not permitting full development of the immune events that ultimately lead to uveitis.

Animals↗
PubMed1983

Involvement of the pineal gland in rats with experimental autoimmune uveitis.

Pineal glands of rats with experimentally induced autoimmune uveitis (EAU) were studied histologically. Inflammatory changes, characterized by mononuclear infiltration, were found in the pineal glands of one-third of the Lewis rats that developed EAU by active immunization with S-antigen. No changes in the pineal gland were observed in AVN rats which are "low responders" for EAU and did not develop ocular disease. Frequency and severity of both pineal gland and ocular involvement clearly were elevated by intravenous injection of Bordetella pertussis along with the S-antigen immunization; all B. pertussis-treated rats of both Lewis and AVN strains developed pineal and ocular changes. Inflammatory changes of the pineal gland also were found in rats in which EAU was induced passively by transfer of lymphocytes from S-antigen-immunized donors. The frequency of involvement of the pineal gland was found to be lower than that of the retinas in rats where EAU was induced by active immunization or by adoptive transfer of lymphocytes.

Animals↗
PubMed1983

Macrophage mediated damage to rat lenses in culture: a possible model for uveitis-associated cataract.

Rat lenses incubated in the presence of "activated" murine peritoneal macrophages are markedly impaired in their ability to accumulate certain radio-labeled compounds from the culture medium whereas incubation with resident macrophages has no such effect. The damage to the lens can be prevented in part by addition of certain antioxidants to the culture medium. The results suggest that mediators released by activated macrophages may be involved in initiation of the cataracts associated with chronic ocular inflammation.

Animals↗
PubMed1982

Modulation of experimental autoimmune uveitis with cyclosporin A.

Cyclosporin A has been shown to be an effective inhibitor of T cell-mediated diseases. We show here that cyclosporin A was capable of totally preventing the clinical appearance of experimental autoimmune uveitis in Lewis rats, even when administered on an every-other-day schedule (10 mg/kg) or when begun seven days after immunization (40 mg/kg). At lower doses of the drug, a modulation of the disease was seen with evidence of a more chronic, granulomatous process. A long-lasting unresponsive state to the immunizing antigen was not uniformly induced with cyclosporin A if therapy was begun seven days after S antigen immunization. Because of cyclosporin A's effective control of this experimental model that is induced by an antigen to which certain patients with uveitis demonstrate cell-mediated immune responses, cyclosporin A may be an effective mode of therapy for T cell-mediated intraocular inflammatory disease.

Animals↗
PubMed1982

Experimental autoimmune uveitis in the athymic nude rat.

A single injection of the retinal soluble antigen (S-Ag, 30 micrograms) to the Lewis or the heterozygous (rnu/+) rats induces a severe bilateral uveitis, characterized initially by infiltration of the retina with inflammatory cells. The athymic nude rat (homozygous rnu/rnu), which lacks the thymus gland and T cell-mediated functions, does not develop ocular inflammatory disease, clinically of histologically, after repeated challenges with S-Ag. Circulating anti-S-Ag antibodies were found in S-Ag-immunized Lewis rats and in the heterozygous, but not the athymic nude rats. Good proliferative responses to concanavalin A, S-Ag and purified protein derivitive of tuberculin (PPD) were found in lymphocyte cultures prepared from the draining lymph nodes of immunized heterozygous rats, but not when lymphocytes from the athymic nude rats were used. Uveitis could be induced in the athymic nude rat when lymphocytes from S-Ag-immunized heterozygous rats were transferred to them. By stimulating the donor lymphocytes in vitro with S-Ag before transfer, the number of recipients that developed uveitis was increased. On the other hand, it was impossible to transfer disease with hyperimmune serum alone. The possible role of T lymphocytes in the induction of experimental autoimmune uveitis with S-Ag is discussed.

Animals↗
PubMed1981

Induction of ocular inflammation by synthetic mediators.

Chemotactic mediators, N-formylmethionyl-leucyl-phenylalanine (FMLP) and the complement component C5a, were injected into the rabbit cornea, vitreous, and skin to induce a reaction resembling the "Arthus phenomenon." Injection of these mediators induced edema and granulocytic infiltration in the cornea, conjunctiva, and skin. These histologic changes resembled the inflammation produced by antigen (ovalbumin [OVA]) in specifically immunized rabbits. Keratitis began after two hours and subsided six hours after the injection. Conversely, the vitreous response started six hours after injection of FMLP and C5a and peaked between 24 and 48 hours. All the inflammatory reactions induced by FMLP, C5a, and rechallenge with antigen could be inhibited in varying degrees by subconjunctival injection of 0.1 mL of 10(-5)M dexamethasone, quinacrine, 5,8,11,14-eicosatetraynoic acid (ETYA), or indomethacin, agents that suppress different sites of chemotaxis of polymorphonuclear leukocytes. However, only the inflammation induced by FMLP could be inhibited by carbobenzoxy-phe-met, a competitive inhibitor of FMLP.

Animals↗
PubMed1981

Resemblance between rhodopsin kinase and S-antigen induced uveitis.

The retinal S-antigen (S-Ag) has been shown to induce uveitis effectively in subhuman primates, and lymphocytes from patients with certain uveitic conditions show cell-mediated responses to this antigen. Rhodopsin kinase (RK), an enzyme probably unique to the mammalian eye, is reported here to resemble the retinal S-Ag in its capacity to induce uveitis in experimental animals. A histological comparison of rat eyes taken 2 and 3 weeks after immunisation with either RK or S-Ag reveals essentially identical pathological alterations. Ocular inflammation is seen in both the anterior and posterior portion of the globe. Areas of focal degeneration of the photo-receptor layer, from which both the S-Ag and RK are extracted, could be seen in both RK and S-Ag immunised animals. Cells from draining lymph nodes of both groups responded by increased thymidine incorporation when cultured in the presence of either RK or S-Ag. In addition antibodies directed against the S-Ag were detected in both groups. These findings, in addition to the biochemical similarities of these preparations, reported elsewhere, would strongly suggest that RK and S-Ag are one and the same. The identification of potentially uveitogenic ocular antigens could help to reclassify uveitic entities that at present have clinically similar courses.

Animals↗
PubMed1981

Cyclosporin a. Inhibition of experimental autoimmune uveitis in Lewis rats.

Cyclosporin A (CS-A), a selective inhibitor of T lymphocytes, is reported here to prevent S antigen (S-Ag) induced uveitis in Lewis rats. The S-Ag, found in all mammalian retinas, is uveitogenic under experimental conditions and patients with certain uveitic entities demonstrate cell mediated responses to this antigen. Daily treatment with CS-A (10 mg/kg) begun on the same day as S-Ag immunization totally inhibited the development of the uveitis in this experimental autoimmune model. Moreover a greater CS-A dose (40 mg/kg) efficiently prevented the disease process when therapy was started 7 d after S-Ag immunization. Anti-S-Ag antibody titers were observed to be similar in rats either protected or not protected with CS-A. Our data support strongly the need for T cell participation in this disease model. Since ocular inflammatory disease is an important cause of visual impairment, the data further suggest that CS-A may be useful in the treatment of patients with intractable uveitis.

Animals↗
PubMed1981

Selective effects of glucocerebroside (Gaucher's storage material) on macrophage cultures.

Although the enzymatic lesion in Gaucher's disease is well established, little is known concerning the pathogenic mechanisms involved in the clinical manifestations of the disease. In order to obtain insight into this unexplored aspect of Gaucher's disease, we examined the effects of glucocerebroside (GL(1)) at the cellular level in monolayers of cultured murine macrophages. The addition of GL(1) to these cultures stimulated the macrophages to release increased amounts of lymphocyte-activating factor (LAF) and lysosomal enzymes into the medium. These responses were proportional to the amount of GL(1) added to the culture. At higher levels of GL(1) (>/=20 mug/ml), lactic dehydrogenase, a cytoplasmic enzyme was also released indicating cellular damage at these doses. Intracellular LAF also increased in macrophages incubated with the high doses of GL(1), demonstrating an increase in total LAF production by these cells. Lipopolysaccharide acted synergistically with GL(1) and stimulated the release of exceedingly high levels of LAF which had a molecular weight profile similar to that of LAF released by exposure to lipopolysaccharide alone. Unlike GL(1), galactocerebroside, sphingomyelin, and ceramidetrihexoside, exerted little or no effect on the release of macrophage products. The effect of GL(1) was selective for macrophages since addition of this material to mouse lens epithelial cells had no detectable cytotoxic effect and it was only slightly toxic to lymphocytes or P815 cells in concentrations at which macrophages were clearly affected. A direct relationship was observed between the cytotoxicity of the sphingolipids and their accumulation in various cells. Macrophages accumulated large amounts of GL(1) but not sphingomyelin, whereas the other cells examined in this investigation did not accumulate either of these lipids. Human monocytes, like murine macrophages, also release increased amounts of LAF when incubated with GL(1). The effect of GL(1) was dose-responsive and synergy was found with lipopolysaccharide. The relevance of these findings to the pathogenesis of Gaucher's disease is considered.

Acetylglucosaminidase↗
PubMed1981

Dissociation between humoral and cellular immune responses to lens antigens.

Rabbits immunized against lens extracts from various other (xenogeneic) species reacted well with the immunizing lens extracts by immunological assays measuring either humoral or cellular immune responses. A dissociation was observed, however, between the humoral and cellular immune responses when lenses from rabbit (allogeneic) or from nonimmunizing species were tested. Antibodies from these rabbits cross-reacted with lenses from rabbit or all other tested species, with levels similar to those obtained with the immunizing lens extracts. The antibodies were determined by both serological tests and the Arthus skin reaction. On the other hand, these rabbits failed to cross-react with rabbit or nonimmunizing animal lens extracts by the cell-mediated delayed skin reaction, and their lymphocytes reacted poorly in culture with the nonimmunizing lenses. A similar dissociation between the humoral and cellular responses was found in rabbits immunized against allogeneic lens. Most of these rabbits produced moderate levels of lens antibodies demonstrated by the serological tests and the Arthus skin reaction but failed to exhibit delayed-type hypersensitivity, and their lymphocyte cultures reacted poorly or not at all to the rabbit or other lenses. The results are discussed in view of their relevance to the hypotheses concerning the pathogenesis of phacogenic uveitis.

Animals↗
PubMed1981

RCS rat macrophages exhibit normal ROS phagocytosis.

Peritoneal macrophages from RCS rats exhibit phagocytic capability equal to that found in macrophages from normal strains of rat. The similarity in phagocytic activity was found with rat or bovine rod outer segments as well as with dystrophic retinal debris. Thus the genetic defect in RCS pigment epithelium is not expressed in the macrophages, which are available to clear the debris layer that accumulates in dystrophic RCS retinas.

Animals↗
PubMed1980

Altered suppressor-cell activities in uveitis.

Suppressor-cell function was evaluated by two in-vitro assay systems in forty patients with intraocular inflammatory disease (uveitis) and in sixteen healthy age-matched controls. A concanavalin-A (Con A)-induced suppressor-cell assay showed that patients with posterior uveitic conditions had greater suppressor activity than did the anterior uveitic group or the control group (p < 0.005); but an assay for non-induced suppressor-cell activity showed that the posterior uveitic group had less suppressor activity (p < 0.001). These findings suggest (a) that at least two cell types may be involved in immunoregulation, and (b) that not all diseases of presumed autoimmune origin are the result of reduced suppressor activity, which has been shown in some "autoimmune" conditions.

Adult↗
PubMed1980

Cellular immune responsiveness of uveitis patients to retinal S-antigen.

S-antigen, an organ-specific substance isolated from the retinal photoreceptor region, was shown to be a potent agent for the induction of experimental autoimmune uveitis. S-antigen and other ocular antigens were tested for their ability to induce blast transformation of lymphocytes from patients with a variety of ocular inflammatory diseases. Lymphocytes from 22% of patients tested manifested a positive memory response to the S-antigen prepared from bovine eyes. Responses to human S-antigen paralleled those found with the bovine. All of those with a positive response had active or inactive retinal lesions. Some posterior uveitis patients responded to crude retinal extracts but not to S-antigen, indicating the possible role of other retinal antigens still to be purified. Control subjects did not manifest a positive immune response to the S-antigen, nor did patients with anterior uveitis. Possibly, these responses play some role in the pathogenesis of the disease.

Adult↗
PubMed1980

Inhibition of DNA and RNA synthesis in lymphocyte cultures by rod outer segments and its counteraction by vitamin E and other antioxidants.

Bovine rod outer segments (ROS) specifically stimulate DNA synthesis in lymphocyte cultures from guinea pigs preimmunized with ROS. At doses above 10 microgram/ml protein, however, preparations of ROS inhibit DNA and RNA synthesis by the sensitized lymphocytes or by normal lymphocytes reacting to mitogens. The inhibtion of RNA synthesis becomes apparent after 24 hr of incubation, whereas little effect was detected after 6 hr. Of the lymphocytes tested, those from mouse and guinea pig spleen were the most susceptible to the effects of ROS, whereas were completely refractory to tested doses of ROS. Bovine retina homogenates were moderately inhibitory, whereas the corresponding cytosol fractions had no detectable effect. Intact ROS were less inhibitory than the disrupted ones, but only minimal amounts of inhibitory activity leaked from disrupted ROS during incubation. Two ROS components, retinoids and docosahexaenoic acid, were also inhibitory to the lymphocytes. The effects of ROS, retinoids, or docosahexaenoic acid were counteracted by antioxidants, with alpha-tocopherol (vitamin E) providing the best protection against ROS. These data thus show lymphocyte cultures to be useful for studying the damaging potential of ROS components and the essential role of antioxidants in protecting the retinal tissues.

Animals↗