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Biomedical subjects

K Nouza

Publications and source records attributed to K Nouza.

At least 37 records · Page 2Linked to original sources

[Cell-mediated immune reactivity to sperm in disorders of human reproduction].

Besides the pathological anti-sperm humoral immunity, pathological anti-sperm cell-mediated immunity is considered as a crucial facet of the disturbances of human reproduction (male and female infertility, recurrent abortions, endometriosis, late EPH gestosis, fetal hypotrophy). A precise and objective method is designed, based on a one-step agarose Leukocyte Migration Inhibition Factor assay. The migration areas are evaluated by a computer-assisted image analysis system. Optimal concentrations of leukocytes and sperm, as well as technical conditions are described. The Radius Migration Indexes and Area Migration Indexes are computed and expressed as a Migration Index percentage for each patient or control. Preliminary clinical results indicate a highly significant association between leukocyte migration inhibition and cases of "immunopathological" infertility and repeated fetal loss.

Cell Migration Inhibition↗

Immunology and immunopathology of reproduction.

This review is dealing with the roles of the immune system in the development and functions of the male and female reproductive systems. Further, it describes the topical views on the roles of immunopathologic events and mechanisms involved in the male and female infertility, recurrent abortions, endometriosis, EPH gestosis and disorders of fetal development. Particular attention is paid to the complicated immunological cross-talk and interplay between the mother and its offspring, including the active role played by the placenta and mainly the trophoblast tissue, in the course of gestation. In the light of the "immunotrophic theory", maternal immune responses to foreign fetal components, occurring in normal pregnancies, within the limits of "tolerated" or even beneficial levels, are described. Emphasis is given on the possible deregulation of materno-fetal immunological balance, leading to immunopathological events and putting in danger the overall reproductive capacity of the couple. The contemporary therapeutic--mainly immunological--approaches to the main reproductive failures are also mentioned.

Female↗

[Comparison of the immunomodulating properties of the cyclosporin Sandimmune (Sandoz) with the newly developed Consupren (Galena)].

An experimental comparative investigation provided evidence of identical immunomodulating properties of the Swiss cyclosporin A of Sandoz Company (Sandimmune) and the Czechoslovak cyclosporin of Galena Company (Consupren). Both preparations administered by the oral route to mice in low doses stimulated the reaction of the late hypersensitivity and in higher doses they inhibited markedly this reaction. Immunostimulation was also observed when influencing the host's reaction against the graft by low doses of the substance. The systemic reaction of the graft against the host was markedly suppressed by repeated doses. The development of antibody-producing cells in the spleen was markedly inhibited by high as well as small doses of the preparations. Inhibition of the formation of total antibodies is caused by inhibition of IgG formation, while IgM formation is enhanced and persists longer. This phenomenon is due to a block of the shift from IgM to IgG formation. In the allogenic tumour model both preparations caused a dose-dependent temporary immunosuppression.

Animals↗

Bacterial endotoxins: comparison of mitogenic, polyclonal, antibody-inducing and toxicity activities.

The mitogenic effects on mouse spleen lymphocytes were determined in a large series of commercially available and laboratory-prepared lipopolysaccharides (LPS) obtained from Escherichia, Salmonella, Serratia and Shigella species; part of these LPS preparations was chemically modified prior to testing. In order to establish whether the degree of mitogenic activity corresponds with other biological effects of these preparations, polyclonal activity, capability to induce specific antibody formation and toxicity were determined for selected LPS's with different mitogenic effects. Some of the detoxication procedures used succeeded in reducing the toxicity of LPS while preserving its high mitogenic activitione of the Fe-detoxified preparations of LPS (from the R-form of Shigella dysenteriae serovar 1) exhibited a medium-degree efficacy in all parameters studied. Generally, there was no correlation between the degree of mitogenic activity and the polyclonal and antibody-inducing activities, but in some instances polyclonal activity did correlate with the antibody-inducing activity.

Animals↗

Preclinical screening and analysis of the immunotoxic and immunomodulatory activity using a multiple immunoassay (MIA) in mice.

Screening and analysis of immunotoxic and immunomodulatory activity has become an integral component in preclinical studies of pharmaceuticals and xenobiotics. In an attempt to replace laborious and expensive batteries of assays used at present we developed a multiple immunoassay (MIA) enabling the determination, in a single mouse, of: the weight of the thymus, spleen and a group of lymph nodes; delayed type hypersensitivity and antibody response to SRBC; phagocytic activity of peritoneal macrophages and the responsiveness of spleen lymphocytes to "T" (PHA, ConA) and "B" (LPS) mitogens in vitro. The MIA responsiveness to two prototype immunostimulators (Thymostimulin and Listeria factor Ei) was tested at two time periods after antigenic stimulation, not only in normal mice, but also in animals with selectively depressed T-systems (anti-Thy1.2 monoclonal antibody) and B-systems (cyclophosphamide); in both dexamethasone-treated and irradiated animals. The findings indicate, that this MIA is capable of reflecting both immunosuppressive and immunostimulatory activities of the tested agents and permits partial insight into the mechanisms underlying these activities.

Adjuvants, Immunologic↗

Functional heterogeneity of Sarcoma I cells in transplantation experiments.

Cell suspensions prepared from Sarcoma I (SaI) allografts at various stages of development in C57BL10/ScSn (B10) mice immunosuppressed with xenogeneic antithymocyte serum (ATS) were adoptively transferred into secondary syngeneic (A/Ph) and allogeneic (B10) recipients. In the syngeneic recipients, a gradual decrease in the tumorigenic capacity of transferred suspensions was proved, while in the allogeneic recipients the tumorigenic activity was proved in early and late periods. The suspensions from the period of both permanently and temporarily regressing tumors showed a suppressed growth capacity in syngeneic and immunosuppressed allogeneic recipients. On the other hand, the suspensions from growing tumors produced in both types of secondary recipients a sharp and permanent growth. The data obtained suggest changes in functional properties of SaI cells during the course of their development in allogeneic recipients.

Animals↗

[Thymosin fraction 5. Preclinical study].

Thymosin fraction 5 from the Research Institute for Pharmacy and Biochemistry possessed the immunomodulatory activity in performed tests. The activity is manifested mostly by the induction of the maturation and the differentiation of T cell precursors, which are released from thymus to secondary lymphoid organs. Thymosin fraction 5 causes the expression of the surface membrane markers Thy-1.2, Lyt-2 and L3T4 on the immature T lymphocytes as well. The induced cells are immunocompetent and able to exert the complete functional activity. In the intact mice thymosin fraction 5 had not pronounced effect on the functional potency of mature immunocompetent cells, but in MTA influenced mice its stimulatory effect on the proliferative response to mitogens and on the antibody production against the T-dependent antigen was demonstrated. Thymosin fraction 5 influenced positively not only the components of the specific immunity, but also the functional activity of peritoneal macrophages. The toxicity of thymosin fraction 5 was in the battery of tests in vitro and in vivo very low and therefore it can be considered to be harmless for the clinical practice.

Adjuvants, Immunologic↗

The immunological properties of listerial complex Ei.

Factor Ei, besides exerting toxic reactions, is amphipathic, antigenic, chemotaxinogenic, causes blastic transformation, adjuvant effect, hypersensitivity (MIF, skin test), activates the RES (splenomegaly), increases the macrophage production, prevents listerial infection in mice, mycobacterial infection in guinea pigs and enhances the effect of BCG experimental tuberculosis and neoplasia in mice (Sa 180).

Animals↗

Immunomodulatory action of double-stranded RNA in unirradiated and irradiated mice.

Double-stranded RNA (ds RNA) stimulates the regional graft-versus-host reaction (GVHR) in mice irradiated with 3 Gy or 5 Gy (but not 7 Gy) of gamma-rays; in control animals GVHR is not influenced. Sensitization of animals to delayed-type hypersensitivity (DTH) reaction is suppressed by ds RNA in both irradiated and unirradiated mice. In the antibody formation to sheep and blood cells (SRBC) ds RNA given before immunization inhibits the switch of IgM to IgG. When injected simultaneously with or after immunization, ds RNA markedly stimulates antibody formation. The differences in the influence of ds RNA on individual immune reactions can be explained by its different action on the regulatory mechanisms.

Animals↗

Immunomodulatory properties of monoclonal anti-Thy-1.2 antibody in vivo.

Monoclonal mouse anti-Thy-1.2 antibody of IgG3 isotype (MTA) inhibits in a significant and long-term manner the regional graft-versus-host reaction (GVHR) when administered to donors as well as to recipients. The process of sensitization in the reaction of delayed type hypersensitivity to SRBC (DTH) is, on the other hand, suppressed only if MTA is administered immediately prior to sensitization. If the time interval between the injection of MTA and of SRBC is extended, the resulting DTH is stimulated. Similarly, the titers of total Ig against SRBC are decreased only if MTA is administered shortly before immunization. Contrasting effects of MTA on the production of IgM and IgG were observed. While the production of IgG was inhibited even after the time interval between the administration of MTA and immunization had been increased, the production of IgM antibodies was stimulated. In recipients of allogeneic Sarcoma I treated with MTA, the primary growth of the tumor is enhanced and the percentage of permanent progressors is increased. Mechanisms of MTA activity are discussed.

Adjuvants, Immunologic↗

Comparison of the effects of anti-Thy-1.2 monoclonal antibody and xenogeneic antithymocyte serum on the development of SaI tumor allograft in mice.

Using the model of Sarcoma I (SaI) (H-2a) tumor allograft transplanted to normal B10 (H-2b) mice and to B10 mice pretreated with ATS, we studied the effects of anti-Thy-1,2 monoclonal antibody (MTA) and compared them with those of rabbit polyvalent antiserum against mouse thymocytes (ATS). When administered shortly before tumor transplantation, MTA showed immunosuppressive effects, at one dose identical to those of ATS, at two doses exceeding ATS effects. In the period following the transplantation of SaI to normal mice, single doses of MTA and ATS showed weak antitumor effects. In mice immunosuppressed with ATS before the tumor transplantation the effects of each agent differed: MTA showed opposite immunomodulatory effects depending on the period of its administration, while ATS supported the primary growth of tumors independent of the time of administration. The results indicate that the immunomodulatory influence of MTA on the development of the tumor allograft is more selective than that of ATS.

Animals↗

Immunodiabetes in rabbits.

The changes of basal glycemia and of that during the glucose and insulin tolerance tests as well as of the production of hemagglutinating antibodies in rabbits immunized with crystalline insulin (CI), chromatographically purified insulin (CPI) and waste products of the chromatographic purification of insulin (WP), both with and without complete Freund's adjuvant (CFA) were studied. Following immunization with CI and its components the glycemia increased characteristically and the course of glucose and insulin tolerance tests was changed. The peak levels of antibodies were found following immunization with WP, while the lowest ones appeared following the application of CPI. Following the immunization with a mixture of antigens with CFA higher levels of antibodies were usually observed than following the administration of antigens without adjuvant. No association was found between the titers of antibodies and glycemia values. The principal morphological change in immunized animals was found to be a partial degranulation of B-cells, often accompanied by hyperplasia of A-cells. In groups immunized with CI or CPI mixed with CFA we detected even insulitis, which was absent in the other groups. Following immunization with CI mixed with CFA such cells were found whose granules in the ultrastructure showed conspicuous similarity to those of foetal (immature) rabbit B-cells. It was assumed that in insulin immunized rabbits the initial damage of islets was followed, at least in some regions, by reparative processes. This was indicated by the findings of mitosis figures in B-cells as well as by the islet A-cell hyperplasia.

Animals↗

Modulation of cell-mediated immunity with 5-azapyrimidine nucleosides.

5-azacytidine [5-AzCR] and 5-aza-2'-deoxycytidine [5-AzCdR] can produce an immunosuppressive or an immunostimulatory effect on the graft-versus-host or host-versus-graft reactions in the regional popliteal lymph node of the mouse. The result depends on the dose of the drug and the time between its administration and induction of the cell-mediated immune response. Syngeneic spleen cells are capable of inducing regional lymphadenomegaly if injected into the footpads of recipients treated 1 day previously or concurrently with 5-AzCR or 5-AzCdR. Spleen cells from allogeneic and syngeneic donors treated with 5-AzCR or 5-AzCdR in vivo or in vitro can elicit greater regional lymphadenomegaly than the untreated cells. Both drugs not only seem to influence the proliferative activity of effector and regulatory populations of immunocompetent cells, but they probably also change their recognition ability and immunogenic properties.

Adjuvants, Immunologic↗

Lentil lectin inhibits cells producing graft-versus-host reaction but does not suppress hematopoietic stem cells in mice.

Treatment of mouse donors or recipients of allogeneic spleen cells with repeated injections of lentil lectin markedly suppressed regional and systemic graft-versus-host reactions. The lectin acted selectively on lymphoid cells; hematopoietic stem cells were largely left unaffected. Repeated administration of the lectin decreased the number of lymphocytes and red blood cells and the amount of hemoglobin; other white blood cells increased in number.

Adjuvants, Immunologic↗

Modulation of the effects of cyclophosphamide on the lymphoid system of mice by double-stranded RNA.

The ds RNA, an inducer of interferon, displayed a marked modulatory action on damage induced in the lymphoid system of mice by a single injection of cyclophosphamide. Its action depended on the type of lymphoid tissue and on the time interval between injection of ds RNA and CY. The "unwanted" synergy between the action of ds RNA and CY was most pronounced in the thymus in which a further great decrease in weight and cellularity was observed at all time intervals. In the case of the spleen and lymph nodes, the undesirable synergy was manifest only when the ds RNA was injected prior to CY. Simultaneous injection of ds RNA and CY, or injection of ds RNA after CY, had beneficial effects on the weight and cellularity of lymphoid organs, possibly by accelerating the regeneration processes.

Animals↗

A study of the role of macrophages in the graft-versus-host reaction.

Resting PEC and fractions of spleen cells adherent to nylon wool (NASC) or polystyrene (PASC) from A/Ph mice evoke a weak regional GVHR or no systemic GVHR in (B10 X A/Ph)F1 hybrids. Blockage of macrophages in vivo by silica or silica gels or removal in vitro of cells phagocytosing iron particles did not change GVH reactivity of A/Ph spleen cells. Addition of PEC or NASC from A/Ph mice to the A/Ph spleen cell suspension somewhat suppressed regional GVHR but enhanced systemic GVHR. Addition of PASC from A/Ph mice, conversely, enhanced regional GVHR and suppressed systemic GVHR. Repeated administration of silica and silica gel to the recipients suppressed regional GVHR; a single dose of silica was most effective at suppression when given one day before the cells. Systemic GVHR was not influenced by this treatment of the recipients. The results indicate that macrophages do not directly induce a GVHR, but they serve as important targets in regional GVHR. In regional and systemic GVHR macrophages perform regulatory functions. Macrophages of donor origin may modify both types of GVHR significantly, depending on the source and type of macrophages and the treatment of donors.

Animals↗

Regulatory role of macrophages in tumor allograft development.

In the study of the role of macrophages in antitumor immune response the model of Sa I (H-2a) allograft development in B10 mice (H-2b) treated with xenogenous antithymocyte serum (ATS) was used. In the treated recipients tumor growth was enhanced as compared to untreated mice, subsequently in some of the mice the tumor permanently regressed while in the rest the temporary regression was followed by a secondary progressive growth. To determine the role of macrophages at different periods of tumor development, both silica (which is known to damage the function of macrophages) and double-stranded RNA (dsRNA; which, in turn, stimulated their function), were used. The administration of silica on the day of tumor cell transplantation slightly promoted tumor regression, whereas silica administered on days 7 or 14 after the cell transfer enhanced the secondary growth of the tumor. On the other hand, administration of dsRNA on the day of tumor transplantation promoted tumor growth, whereas, when administered on days 7 or 14, it enhanced the regression of the tumor. An administration of both substances at later periods had no effect on the growth of the tumor. From these results it can be assumed that macrophages at the time of induction of antitumor immune responses participate in the events enhancing the subsequent growth of the tumor allograft, whereas at later times they have an antitumor activity.

Animals↗