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J Madar

Publications and source records attributed to J Madar.

At least 19 recordsLinked to original sources

[Role of sperm antibodies and cellular autoimmunity to sperm in the pathogenesis of male infertility].

OBJECTIVE: To test the hypothesis of relationship between sperm pathology and elevated humoral and/or cell-mediated antisperm autoimmunity in male partners from infertile couples. DESIGN: Analytic study. SETTING: Department of Immunobiology, Institute for the Care of Mother and Child, Prague. METHODS: Sperm samples were evaluated according to WHO rules. Sperm-bound antisperm autoantibodies (ASA) were determined by SpermMar Test (FertiPro N. V., Sint-Martens-Latem, Belgium). For evaluation of cell-mediated antisperm autoimmunity (CMAA) the authors used their own modification of migration-inhibition test (Dimitrov et al., J. Immunol. Methods 154: 147, 1992). RESULTS: The pool of men was divided into groups according to the result of sperm examination: normozoospermia (740 men), asthenozoospermia (244), teratozoospermia (191), oligoasthenozoospermia levis (61), oligoasthenozoospermia gravis (29), oligoteratozoospermia (82), and azoospermia (54). Subgroup of fertile men (32) consisted of normozoospermic men--fathers of child younger than 3 years. Percentage of sperm-bound ASA-positive samples was significantly higher in asthenozoospermia in comparison with normozoospermia in both IgA (20.8% versus 10.6%) and IgG classes (13.8% vs 6.8%). Positivity of CMAA was significantly more frequent in group of asthenozoospermic (52%) than in normozoospermic (28.5%) and fertile (12.5%) men. CONCLUSION: Antisperm autoimmunity, namely its cell-mediated form, appears to play a significant role in impairment of spermiogenesis. Sperm-bound autoantibodies were found more frequently in asthenozoospermia, but also in some men with normozoospermia they may impair fertility.

Autoantibodies↗

Autoimmune antiovarian antibodies and their impact on the success of an IVF/ET program.

In previous papers, we referred to studies of the influence of antiovarian autoantibodies on menstrual cycle disorders in adolescent girls. We examined autoantibodies against ooplasma, zona pellucida, membrana granulosa, theca folliculi interna, and lutein cells. In infertile women in the IVF/ET program, we studied the positivity of antiovarian antibodies and cytokines, namely, TNF-alpha and IL-1 beta, in follicular fluid correlated with the following subgroups, characterized by the outcome of in vitro fertilization, as follows: G, pregnant; F, fertilized; N, nonfertilized; and O, no oocyte gained. The presence of autoantibodies corresponds to the success or failure of the IVF/ET program. Our results support the hypothesis that antiovarian autoantibodies play an important role in both the endocrine and the reproductive function of the human ovary and that it can influence them negatively.

Adult↗

[Use of human sperm protein monoclonal antibodies in the diagnosis of sperm pathology and selection of a suitable assisted reproduction method for fertilization].

OBJECTIVE: Use of monoclonal antibodies against sperm proteins in human medicine. DESIGN: Experimental and clinical studies. SETTING: Dep. Biology and Biochemistry of Fertilization, Institute of Molecular Genetics, Prague, Laboratory IVF, Iscare IVF, Prague, Dep. of Immunobiology, Institute for the Care of Mother and Child, Prague. METHODS: Monoclonal antibodies against human sperm intra-acrosomal and cell surface proteins were used for quantitative analysis of these proteins by the immunofluorescence test in samples of human sperm of good and poor qualities. RESULTS: The detection of intra-acrosomal proteins was decreased and, on the other hand, detection of surface proteins was the same or higher in pathological spermatozoa. CONCLUSIONS: Monoclonal antibodies can be used for diagnostics of sperm pathology (quantitative detection of proteins) and for evaluation of the physiological state of sperm cells (state of acrosome before or after acrosome reaction). Finally, monoclonal antibodies could be useful for selection of a suitable method of fertilization (IUI, standard IVF, ICSI) in the laboratories of assisted reproduction.

Acrosome↗

Surfactant-deficient respiratory distress after elective delivery at 'term'.

Babies of 37-41 wk gestation are, by international convention, said to be born at 'term', but some still develop respiratory distress. It is not clear how mature a baby has to be to be free of risk of primary surfactant deficiency. An area-based retrospective study of all the 179,701 babies of 34 or more weeks' gestation born alive in a defined area of the north of England in 1988-92 identified 149 babies with features of respiratory distress typical of surfactant deficiency severe enough to be managed with ventilatory support and with no evidence of aspiration or intrapartum infection. Gestation was carefully cross-validated against antenatal information, including at least one ultrasound assessment in the first half of pregnancy. Thirty-six of these babies were born at or after 37 wk gestation. Only 4 of the 35 delivered at 37-38 wk went into spontaneous labour. Seven became ill enough to be candidates for ECMO and two died. A review of all neonatal deaths in the study area between 1981 and 1995 identified four similar deaths in 1981-87 and two in 1993-95. Babies who are not premature, using the internationally agreed definition, can show signs of potentially lethal pulmonary immaturity at birth, especially if subjected to pre-labour Caesarean delivery. Those born at 37-38 wk are 120 times more likely to receive ventilatory support for surfactant deficiency than those born at 39-41 wk. Elective delivery should only be undertaken before 39 wk gestation for good medical reasons.

Cesarean Section↗

[Practical results of monitoring pregnancy in women with systemic lupus erythematosus].

BACKGROUND: The authors dealt with the urgent problem under what conditions it is possible to achieve in a woman with systemic lupus erythematosus (SLE) or another collagenosis, or secondary antiphospholipid syndrome (APS) a favourable outcome of pregnancy and the delivery of a healthy infant. METHODS AND RESULTS: The investigation comprised 23 women incl. 20 with SLE, two with the mixed form of a diffuse connective tissue disease (MCTD) and one with Sjögren's syndrome of the primary type. From the total number of 20 pregnancies six were consulted in advance with a doctor (group I-s-called planned pregnancies) and all terminated by a successful delivery. Of 11 pregnancies which were not consulted with a doctor in advance (group II-so-called unplanned pregnancies) 9 were terminated in term, however, only 5 with a successful delivery (55.5%), two women are still pregnant. Exacerbation of the basic disease during pregnancy was recorded only once and did not lead to discontinuation of the pregnancy. CONCLUSIONS: The authors provide evidence that desired pregnancy of informed women suffering from SLE or another collagenosis when assisted by a specialized medical team can lead to a successful delivery of an infant.

Adult↗

Correlation of asthenozoospermia with increased antisperm cell-mediated immunity in men from infertile couples.

To investigate whether cell-mediated immunity (CMI) against sperm and/or antisperm circulating antibodies are associated with poor semen quality, a leukocyte migration inhibition factor (LMIF) assay and an enzyme-linked immunosorbent assay (ELISA) were performed in groups of men from infertile couples, men from fertile couples and sperm donors. Twenty-five of 102 men (25%) revealed positive CMI against sperm and 10 (10%) had positive antisperm antibody titers in their sera. Fifteen of 28 asthenozoospermic men (53%) from infertile couples revealed positive antisperm CMI. The incidence of antisperm CMI was significantly increased (P < 0.05) in the infertile men with asthenozoospermia compared with the men from the other two groups (men from fertile couples and sperm donors). No significant differences between migration indices were seen when such a comparison was done for oligoasthenoterato- and teratozoospermics. The results indicate that increased antisperm CMI is associated with asthenozoospermia in a significant number of men from infertile couples. The importance of these findings is discussed.

Autoantibodies↗

Immunological properties of heterozygous nu/+ mice: changes in antibody response and inducibility of tolerance to protein antigens.

Heterozygous nu/+ mice are not fully identical in their immunological properties with the mice of wild +/+ genotype. A colony of nu/nu, nu/+ and +/+ mice from the same breeding nucleus was established and their immune reactivity to human serum albumin, inducibility of adult immune tolerance to hen egg lysozyme (HEL), sensitivity of their lymphoid cells to stimulation by mitogens and ratio of CD3, CD4 and CD8 positive cell populations was studied. Both the numbers of antibody-forming cells in regional lymph nodes and the antibody titres in sera of nu/+ mice were highly variable, between undetectable values of nu/nu and high values of +/+ homozygotes. Intravenous pretreatment with soluble HEL, leading in +/+ mice to a deep hyporeactivity to subsequent immunization with the same antigen, did not decrease the response of nu/+ mice significantly. These results indicate that the immunological alteration of nu/+ mice is not only quantitative and that T cell subpopulations might be differentially modified by the presence of nu allele. The finding of decreased CD4:CD8 ratio in nu/+ mice also supports this idea.

Animals↗

Corticosterone treatment affects neonatal induction of immunological tolerance to hen egg lysozyme in mice.

Immunological tolerance to hen egg lysozyme (HEL) was induced in mice by one injection of 0.1 mg of HEL intraperitoneally on day 0 (i.e. within the first 24 h after birth). After immunization with the same antigen 8 weeks later, such mice developed markedly lower numbers of specific antibody-forming cells than did the untreated controls. When the tolerized mice were injected with three doses (1 microgram each) of corticosterone (CN) on days 1, 3 and 5, the tolerogenic effect was markedly diminished. However, in adult animals neither the inducibility of tolerance nor the intensity of immune reaction was influenced by the early treatment with CN. No influence of early CN treatment on the in vitro response of spleen cells to T- and B-cell mitogens was found, when tested in adult animals. The results support a view that neonatally induced immunological tolerance to hen egg lysozyme is mediated by a population of antigen-specific regulatory cells, generation of which can be prevented by treatment with CN.

Animals↗

Increase by bacterial lipopolysaccharide of antibody production in mice rendered hyporesponsive to lysozyme.

The effect of bacterial lipopolysaccharide (LPS) on the immune response of adult mice to hen egg lysozyme (HEL) was studied under conditions in which hyporesponsiveness to HEL was induced by: (i) the intravenous injection of syngeneic spleen cells incubated with HEL; (ii) the intravenous administration of soluble HEL, and (iii) the intraperitoneal injection of HEL in IFA. In all cases, mice were immunized by footpad injection of HEL, with or without LPS. The antibody response produced was measured by the number of indirect anti-HEL plaque forming cells (PFC) detected in popliteal lymph nodes. The incorporation of LPS in the immunizing dose of HEL had little effect on the response of controls; however, it resulted in an appreciable increase in the antibody response of all three groups of hyporesponsive mice. Although, after treatment with LPS, the number of PFC detected in mice made tolerant by spleen cell injection approached those of the controls, lower increases in the antibody response were noted for the remaining two groups of hyporesponsive mice.

Animals↗

IL-2 influences the balance between immunity and unresponsiveness in the picryl (TNP) contact sensitivity system by blocking the development or action of an Lyt-2+, I-J+ T suppressor cell.

Mice injected with antigen (picrylated spleen cells) intravenously fail to develop contact sensitivity. However, contact sensitivity occurs if these mice are injected with IL-2. This effect of IL-2 was reproduced in vitro by taking spleen cells 2 days after injecting antigen intravenously and culturing them with either 150 u/ml recombinant IL-2 for 2 days or by pulsing with 600-1200 u/ml IL-2 at 4 degrees C for 1 hr. After 2 days in culture these antigen-exposed cells transfer contact sensitivity to naive recipients in a 24-hr experiment. However, the ability of antigen-exposed cells, pulsed with IL-2, to transfer contact sensitivity is abolished when they are incubated with unpulsed antigen-exposed cells and as few as 1/16 of their number have a significant effect. This phenomenon is specific, as normal cell or cells from mice injected with oxazolonated cells intravenously have no effect. The suppressor cells were Thy-1+, Lyt-1-, 2+, I-J+ T cells. It was concluded that IL-2 prevents the development/action of antigen-specific T suppressor cells.

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↗

Generation of lymphokine-activated killer cells does not require DNA synthesis.

We studied the role of DNA synthesis in the induction of lymphokine-activated killer (LAK) cells by recombinant interleukin-2 (IL-2) and the dependence of this phenomenon on DNA synthesis. Doses of gamma-irradiation (1000-5000 rads) that profoundly reduced DNA synthesis in human peripheral blood mononuclear leucocytes (PBL) also effectively suppressed the development of cytotoxic activity in the absence of IL-2. However, the same doses of irradiation affected the induction of LAK activity by IL-2 to a much lesser extent. Blocking the formation of deoxyribonucleotides by hydroxyurea, which resulted in a complete inhibition of DNA synthesis in PBL or purified T lymphocytes, had virtually no effect on the generation of LAK cells. These results indicate that the expression of LAK activity is not dependent on DNA synthesis.

Cytotoxicity, Immunologic↗

The effect of bone marrow regulatory peptides on antibody production by hybridoma cells.

Peptides produced by bone marrow cells (myelopeptides) increase antibody production. Since antibody producing cells seemed to be their targets, we tested in these experiments the effect of myelopeptides on antibody production by 2B2 and 2C12 hybridoma cells. Both hybridomas produce anti-SRBC monoclonal antibodies of the IgM class. The 2B2 cells do not produce direct haemolytic plaques and less than 5% of them produce the indirect ones during the 90-min assay period. When they were cultivated with myelopeptides for 15 h, the number of indirect plaques increased two-fold. A slightly lower increase was observed after 24 h of incubation, while the 48-h incubation period did not increase the number of detected plaques. After 6 h of preincubation, only a slight increase in indirect plaque numbers was observed. About 25% of the 2C12 hybridoma cells produce both direct and indirect haemolytic plaques during the assay period. The effect of myelopeptides was studied only on the indirect ones and no clear effect was observed. Only after the 15-h incubation period a slight increase in plaque numbers was observed. Because the myelopeptides affect antibody production of hybridoma cells, antibody producing cells are evidently the targets of these substances. It remains to be established, whether they are the only target cells in the myelopeptide action on the immune response.

Animals↗

The effect of thymectomy on immunological tolerance to human serum albumin in chickens.

The effect of thymectomy performed on the day of hatching has been studied in chickens rendered tolerant by 100 mg of HSA injected also on the day of hatching. After challenge at the age of 6 and 9 weeks, no significant difference was observed between the group of tolerant chickens, in which the thymectomy was complete or incomplete, and the non-operated tolerant one. The delayed recovery from tolerance observed in mammals was not seen even in chickens in which thymus was removed completely and no thymic residue remained. The anti-HSA antibodies were even slightly higher in thymectomized birds than in the non-operated ones but the difference was statistically non-significant.

Animals↗