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Biomedical subjects

I Gery

Publications and source records attributed to I Gery.

At least 127 records · Page 7Linked to original sources
PubMed1985

Analysis of the cytotoxic effects of light-exposed HEPES-containing culture medium.

The addition of N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) to RPMI 1640 medium markedly increases the production of cytotoxic products during exposure of the medium to visible light. The cytotoxicity has been analyzed by measuring uptake of [3H]thymidine by murine thymocytes cultured in preirradiated medium containing 25 mM HEPES. Complete inhibition of thymidine uptake was produced by exposing 50% of the culture medium to light for 3 h before addition of cells. The HEPES-mediated effect requires only that HEPES and riboflavin be exposed to light; other medium constituents are not necessary. Hydrogen peroxide is a principal cytotoxic agent produced in this system. It is demonstrated that most, but not all, of the inhibition of thymidine uptake can be attributed to hydrogen peroxide.

Animals↗
PubMed1985

Kinetics of T-lymphocyte subsets in the eyes of Lewis rats with experimental autoimmune uveitis.

The kinetic changes of T-lymphocyte subtypes in the eyes of Lewis rats which developed experimental autoimmune uveitis (EAU) were studied. Lymphoid cells were the majority of the ocular inflammatory cells in different stages of the disease. As EAU proceeds, there is an increase in the relative number of OX-8 (suppressor/cytotoxic) T cells, and the decrease of W3/25 (helper/inducer) T cells. These findings were also observed in the animals with EAU and partially treated with corticosteroids or cyclosporine. The kinetics may reflect the role of immunoregulation of the inflammatory response in autoimmune diseases.

Animals↗
PubMed1985

T-lymphocyte subsets in experimental autoimmune uveitis.

The dynamic changes of the lymphocyte subsets in the inflamed ocular tissue in Lewis rats with experimental autoimmune uveitis (EAU) were studied by immunohistopathological evaluation at varying intervals after initiation of the disease. Monoclonal antibodies to specific markers of the rat T-helper/inducer lymphocyte (W3/25) and T-suppressor/cytotoxic lymphocyte (OX-8) were used in the avidin-biotin-peroxidase complex (ABC) method. During the early stages of the disease following the acute inflammatory reaction, the T-helper/inducer lymphocytes are found in larger numbers within the infiltrates, the relative number of the T-suppressor/cytotoxic cells is very low during the initial phases, with a ratio as low as 5 to 1. During the later stages, there is a continuous increase in the relative number of suppressor/cytotoxic cells that reaches the ratio of 1 to 1, or even 1 to 2. It is postulated that the observed changes in the ratios between T-helper/inducer and T-suppressor/cytotoxic cells during the different stages of EAU may reflect the kinetics and regulation of the inflammatory response in autoimmune diseases.

Animals↗
PubMed1985

Differences between intra- and extracellular interleukin-1.

The intracellular (IC) and extracellular (EC) pools of interleukin 1 (IL-1) of human monocyte cultures were found to differ in their molecular size and charge characteristics. EC activity was found by Sephadex G-75 chromatography to consist mainly of a single peak in the 15,000-17,000 mol. wt range. In contrast, IC activity was distributed in four peaks (mol. wts of approx. 15,000, 26,000, 45,000 and greater than 70,000). Treatment of a pool of the IC 26,000, 45,000 and greater than 70,000 mol. wt species with CHAPS, a zwitterionic detergent, yielded a large amount of the 15,000 mol. wt species, thus suggesting that a portion of the larger species consists of aggregates of the 15,000 mol. wt molecule. Both IL-1 pools were found by isoelectrofocusing to be composed of three molecular species with pIs of 5.5, 6.7. However, the proportions of these species differed markedly between the EC and IC pools. The large majority of IC activity (approximately 90%) was found at pI 5.5, while 55-60% of EC activity had a pI of 6.7 and 35-40% had a pI of 5.5. The differences in their biophysical properties support the notion that the IC and EC pools of IL-1 also differ in their functions.

Cells, Cultured↗
PubMed1985

The failure of cyclosporin to inhibit granulomatous inflammation in acute Arthus-like panophthalmitis.

Acute Arthus-like panophthalmitis (AP) was induced in Lewis rat eyes by lens injury after immunization with whole rabbit lens extract. AP consists of an acute anterior ocular inflammation, followed by a posterior choroidal granulomatous reaction. Neither inflammatory response was inhibited by daily treatment with cyclosporin, 10 mg/kg, beginning on the day of lens injury. Cyclosporin would not be expected to interfere with the lens-induced anterior Arthus-like inflammation. The lack of inhibition of the choroidal inflammation was unexpected. The results are interpreted to indicate that the posterior granulomatous choroidal inflammation is a non-immune reaction initiated by the severe lens-induced Arthus-like reaction.

Animals↗
PubMed1985

Different susceptibilities to cyclosporin A of the mitogenic and potentiating activities of interleukins.

A dissociation was observed between the mitogenic and potentiating activities of interleukins (ILs)-1 or -2 in murine thymocyte cultures treated with drugs. The direct mitogenic effects of the ILs were unaffected by cyclosporin A (CsA) at concentrations which abolished the potentiating activities of these mediators, i.e. their synergy with lectins. Conversely to CsA, dexamethasone was more inhibitory to the mitogenic activity of the ILs than to their synergistic reactions with the lectins. The resistance to CsA of the mitogenic activity of IL-1 was unexpected since this response is assumed to be mediated by newly formed IL-2 and CsA inhibits IL-2 production. This resistance was further tested by coculturing thymocytes with the IL-2-dependent CT6 cells; net gains of thymidine uptake by the cocultures were attributed to IL-2 release. Such net gains were observed in cocultures stimulated with IL-1 alone and were relatively resistant to CsA. On the other hand, net gains stimulated by mitogenic lectins, alone or with IL-1, were eliminated by CsA. These results support the notion that IL-1 direct activity on thymocytes is mediated by newly released IL-2 and show that this IL-1 activity is unusual in being resistant to CsA. Low levels of protection against CsA were also observed in cultures potentiated by IL-1: lymphocytes stimulated by lectins or antigens and IL-1 were inhibited by CsA less than lymphocytes stimulated without IL-1. Yet, this partial protection by IL-1 was achieved only at CsA concentrations about 100 fold lower than those resisted by thymocytes directly stimulated by IL-1.

Adjuvants, Immunologic↗
PubMed1985

Dual effect of phorbol myristate acetate (PMA) on murine thymocyte cultures.

4 beta-phorbol 12-myristate 13-acetate (PMA), a potent tumor promoter, was found to have a dual effect on interleukin 1-(IL 1) stimulated murine thymocyte cultures. In the absence of 2-mercaptoethanol (2-ME) or other sulfhydryl containing compounds, PMA inhibited 3H-thymidine incorporation, while at the same concentrations but in the presence of sulfhydryl agents, PMA exerted a potent stimulatory effect. The other sulfhydryl compounds giving effects resembling 2-ME were dithiothreitol and cysteine, while glutathione and various oxygen radical scavengers (catalase, superoxide dismutase, histidine, alpha-tocopherol or mannitol) had no such effect. 2-ME enhanced the response of thymocytes incubated with PMA even when added 24 h after initiation of the cultures, but not at the 48 h interval. Harvesting the thymocyte cultures at various intervals showed that the inhibitory effect of PMA was already fully pronounced 48 h after initiation of the cultures. On the other hand, the stimulatory effect of PMA on cultures activated with IL 1 in the presence of 2-ME took place mainly during the last 24 h of the 72-h culture period. The modulation of the effect of PMA on thymocyte activation by 2-ME or similar agents may account for the apparent discrepancies in the literature concerning the action of PMA in lymphocyte cultures.

Animals↗
PubMed1985

Effects of cyclosporine and other immunosuppressive drugs on experimental autoimmune uveoretinitis in rats.

Five immunosuppressive and anti-inflammatory agents were tested for their effects on development of experimental autoimmune uveoretinitis (EAU) and immune responses to S-antigen in rats immunized with this retinal antigen. When administered daily from day 0-14 after immunization, cyclosporine at 5-20 mg/Kg was nontoxic and yet effective in inhibiting the development of EAU for at least 30 days. All other tested drugs were found toxic at their immunosuppressive doses. Of these drugs, only cyclophosphamide (at 5-20 mg/Kg) was capable of inhibiting EAU in some of the treated rats for up to 30 days. Other agents, bredinin (40-100 mg/Kg), dexamethasone (0.2-0.4 mg/Kg), or colchicine (0.5 mg/Kg) produced only a delay in the disease onset. Cyclosporine was also unique in its effect on the immune responses of the rats by selectively inhibiting only the specific T-cell-mediated responses to S-antigen (delayed skin response and lymphocyte response in culture), while having no negative effect on antibody production or the lymphocyte response to the polyclonal mitogen, concanavalin A. Other drugs, when effective, inhibited all types of immune response. In addition, cyclosporine was capable of preventing EAU even when given to rats as late as from day 7 after immunization. Only cyclophosphamide (at 20 mg/Kg/day) had a similar effect on 1/3 of the rats, while other drugs only delayed or had no effect on the disease onset when given by this late schedule.

Animals↗
PubMed1985

Adoptive transfer of experimental autoimmune uveoretinitis in rats. Immunopathogenic mechanisms and histologic features.

In order to learn about the immunopathogenic mechanisms of experimental autoimmune uveoretinitis (EAU), the capacity of lymphocytes to transfer the disease was studied. EAU was transferred to naive syngeneic rats by intraperitoneal injection of spleen or lymph node (LN) cells from S-antigen immunized rats, following their incubation in culture with either S-antigen or concanavalin A (Con A). In contrast, the same cells did not cause inflammatory changes in the recipient eyes when injected intravitreally. The identity of the lymphocytes that transfer EAU was determined by using monoclonal antibody enriched subsets of lymphocytes. EAU was transferred by the subset of helper/inducer T-cells, but not by T-cells of the suppressor/cytotoxic subset. Recipient rats of spleen or LN cells cultured with S-antigen exhibited both humoral and cellular immune responses to S-antigen. On the other hand, recipients of spleen cells cultured with Con A developed only cellular immune response to S-antigen. Yet, both groups of recipients fully developed EAU. The clinical and histologic changes in recipient rats closely resembled those in rats in which EAU was induced by active immunization. Severe tissue damage occurred at the photoreceptor cell layer, but inflammatory infiltration also was found in other ocular tissues. Involvement of polymorphonuclear leukocytes (PMNs) was noted throughout ocular tissues even in the eyes of recipients with no detectable antibodies to S-antigen, suggesting that the ocular PMNs infiltration in rats is not necessarily the result of an Arthus-like inflammatory process.

Animals↗
PubMed1984

Cytostatic and cytolytic activities of macrophages regulation by prostaglandins.

Murine peritoneal macrophages (M phi), activated in vivo or in vitro, remarkably inhibited the uptake of thymidine by a lens epithelial cell line, while resident M phi, or M phi induced by thioglycollate, exhibited much lower or no cytostatic capacity. The target cells were partially protected from the cytostatic activity by the anti-inflammatory agents indomethacin, aspirin, and dexamethasone, but not by lipoxygenase inhibitors. The protective activity of indomethacin and aspirin, but not of dexamethasone, was completely counteracted by prostaglandin E2 (PGE2). Yet, PGE2 alone has no effect on the uptake of [3H]thymidine by lens epithelial cells. PGE1 resembled PGE2 in its effect on this system, whereas PGA2, PGB2, or PGF2 alpha had no detectable activity. The counteracting effect of PGE2 was mimicked by dibutyryl cAMP or by cholera toxin, an agent which increases cAMP levels. These findings suggest that PGEs are not direct cytostatic agents, but rather, are essential mediators for the development of the cytostasis. Activated M phi did not lyse cells of the original lens epithelial cell line, but caused substantial cytolysis of cells of a subline derived from it. In contrast to its aforementioned effect on the cytostasis, PGE2 inhibited the cytolytic activity of M phi. Thus, this study provides a first demonstration in a single system of the opposite effects of PGEs on M phi activity on target cells, i.e., mediating the cytostasis and inhibiting the cytolysis.

Animals↗
PubMed1984

Production of intra- and extracellular interleukin-1 (IL-1) by human monocytes.

Human monocytes, separated by adherence and cultured in plastic wells, produced "spontaneously" high levels of intracellular interleukin-1 (IL-1) during the first 20 hr in culture while releasing in most cases less than 10% of it into the medium. The addition of bacterial lipopolysaccharides (LPS), quartz silica particles, zymosan, or phorbol myristate acetate (PMA) enhanced 3 to 50 times the overall production and 25 to 2000 times the release of IL-1. From 24 to 44 hr of culture, the "spontaneous" production and release of IL-1 decreased to negligible amounts. During the same period of time, the addition of silica particles or PMA had clearly less effect while the addition of LPS or zymosan produced high levels of intracellular IL-1 but only a modest release of it. When any of the stimuli was added after the first 48 hr and up to 6 days of culture, no release of IL-1 was detected and only a small amount of the intracellular fraction was seen when using LPS or zymosan. These results were not due to cell death prior to the addition of the stimuli but rather to a decrease in the responsiveness of the mononuclear phagocytes that coincides with their transformation into macrophages. The different patterns of production and release observed with time suggest that synthesis and secretion of IL-1 by human monocytes are two distinct biological events.

Adult↗
PubMed1984

Silica-stimulated monocytes release fibroblast proliferation factors identical to interleukin 1. A potential role for interleukin 1 in the pathogenesis of silicosis.

Previous study strongly suggests that silicotic fibrosis is mediated by macrophages and their soluble mediators. The biochemical properties of the mediators involved in silicotic fibrosis, however, are as yet ill defined. The current study, therefore, determined whether human monocyte-macrophages treated with fibrogenic silica dust released factors capable of activating fibroblasts as measured by an increase in fibroblast proliferation. Silica, but not nonfibrogenic diamond dust, stimulated the release of fibroblast proliferation factors. Moreover, the level of fibroblast proliferation activity was comparable with the level of thymocyte proliferation (interleukin-1) activity in the same culture supernatants. The factors responsible for these seemingly diverse activities were found to behave identically when analyzed by gel filtration chromatography, size exclusion chromatography, isoelectrofocusing, ion exchange chromatography, and hydrophobic chromatography. Moreover, the response of these factors to four different proteases and heat (56 degrees C) was also identical, which shows that their comigration on various separation media could not be explained by noncovalent interaction between otherwise unrelated species. The data demonstrate that a monocyte-derived thymocyte proliferation factor having the molecular properties of interleukin 1 is capable of regulating fibroblast proliferation. In silicosis and other fibrotic diseases, the local release of interleukin 1 may contribute to abnormal connective tissue deposition by stimulating fibroblast proliferation, and thereby, amplifying other signals stimulating the synthesis of connective tissue components.

Cells, Cultured↗
PubMed1984

Cellular and humoral immune parameters among patients with retinitis pigmentosa and other retinal disorders.

Patients with retinitis pigmentosa, other retinal degenerations and a group of normal volunteers were included in a masked study designed to examine the existence of autoimmune reactions toward retinal antigens and the possible defect in lymphokine production (IL-1, IL-2 and gamma interferon). The results obtained did not show any specific anamnestic response to the retinal S-Ag nor any outstanding defect in gamma interferon production by the lymphocytes of patients with retinitis pigmentosa. It is suggested that a larger masked study be conducted as soon as possible in order to clarify these aspects of immune aberrations in patients with retinitis pigmentosa.

Antibody Formation↗
PubMed1984

Purification of retinal S-antigen to homogeneity by the criterion of gel electrophoresis silver staining.

This report describes a procedure by which high performance liquid chromatographic (HPLC) techniques are used to obtain homogeneous S-antigen. Conventionally prepared S-antigen was purified further by fractionation on the anion exchange Mono-Q column followed by gel filtration on a TSK-3000 column. This procedure produced an S-antigen preparation, which appeared homogeneous by gel electrophoresis using the very sensitive silver staining method. The purified material retained its immunochemical and uveitogenic activity. The availability of homogeneous S-antigen will facilitate studies aimed at elucidating, at the molecular level, the mechanism by which S-antigen induces uveitis.

Animals↗
PubMed1984

An association between susceptibility to experimental autoimmune uveitis and choroidal mast cell numbers.

An association was found in rats of different strains between the susceptibility to EAU and the number of mast cells in the choroid of the eye. High responder rats (Lewis, CAR) had strikingly more choroidal mast cells than the low responder BN animals, whereas intermediate numbers of mast cells were found in the F1 hybrids of Lewis and BN (LBNF), which exhibited an average level of susceptibility to EAU. LeR rats, derived from the Lewis strain, developed EAU only when treated with B. pertussis, and their number of choroidal mast cells was only about 1/5 of that found in the Lewis rats. Unlike the differences in the number of choroidal mast cells, small variations were found in the skin mast cell numbers of the tested rats. It is proposed that the number of local mast cells may be one mechanism by which the susceptibility to an organ-specific autoimmune disease is genetically regulated.

Animals↗
PubMed1983

Treatment of intraocular inflammatory disease with cyclosporin A.

Eight patients with bilateral sight-threatening posterior uveitis of non-infectious aetiology that had not responded to corticosteroid or cytotoxic therapy were given cyclosporin A. Seven of the eight responded with improvement in visual acuity and disappearance of ocular inflammatory activity. The seven included two with Behçet's disease, who also had improvement in non-ocular symptoms. Peripheral blood lymphocytes from the seven cyclosporin A responsive patients, but not those from the non-responder, gave positive in-vitro blastogenic responses to the retinal S-antigen, a highly uveitogenic organ-specific material. In four patients OKT4/OKT8 ratios fell after the start of therapy, as the result of an increase in the OKT8 fraction. In the other four patients the fall was preceded by an increase in the OKT4/OKT8 ratio. Cyclosporin A did not influence natural killer cell activity. Side-effects ascribed to cyclosporin A were tolerated or disappeared with continued therapy, sometimes at a lower dosage. No neoplasms were observed. Cyclosporin A seems to be effective treatment for selected patients with severe bilateral uveitis of non-infectious aetiology.

Adult↗
PubMed1983

Effects of lipid peroxidation products on the rat lens in organ culture: a possible mechanism of cataract initiation in retinal degenerative disease.

Rat lenses in organ culture which are exposed to bovine rod outer segments (ROS) or to the major fatty acid of ROS, docosahexaenoic acid, are impaired in their ability to accumulate radiolabeled compounds which lenses normally accumulate by active processes. The extent of lens damage correlates well with the extent of lipid peroxidation in the culture medium as assessed by the thiobarbituric acid assay. Addition of vitamin E to the medium inhibits the effect on the lens while addition of Fe-ADP complexes potentiates the effect. Thus, the lens damage appears to be attributable to toxic species generated by peroxidation of the polyunsaturated lipid added to the culture medium. Toxic aldehyde products appear to be major mediators of the lens damage, since semi-carbazide, which avidly reacts with aldehydes, can protect lenses in this system. These findings may have relevance to the cataracts clinically associated with retinal degenerative diseases such as retinitis pigmentosa. The highly membranous photoreceptor cells are extremely rich in polyunsaturated lipid. Degeneration of these cells, which is the primary pathology in such diseases, would likely lead to peroxidation with generation of toxic products within the eye. Such products could potentially produce secondary damage to other ocular structures including the lens.

Animals↗