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Biomedical subjects

J Madar

Publications and source records attributed to J Madar.

At least 19 recordsLinked to original sources

[Immunopathological and histopathological aspects of ectopic implantation with possible effect on fertility disorders].

OBJECTIVE: To evaluate leucocytic infiltration of fetomaternal interface in ectopic pregnancy and to evaluate the changes in cell immunity against trophoblast (AT-CMI) in women with extrauterine pregnancy (GEU) in their medical history. To assess the effect of these factors on possible fertility disorders in a woman. DESIGN: A retrospective study. SETTING: Mother and Child Care Institute, Prague. METHODS: In most of the patients, we addressed GEU through laparoscopy. The tube was extirpated in toto and immediately fixed in Baker's solution. Thereafter, it was prepared in a dissection microscope and then processed in a standard way. In order to identify the intensity of AT-CMI, we used the leucocyte migration inhibition test. The cytotrophoblastic cell line JAR was used as an antigen. The degree of inhibition of the migration was monitored by means of a computer image analyser. Inhibition of migration below 75% was rated as favourable. RESULTS: We monitored the presence of inflammatory infiltrate in the place of implantation and correlated the findings with the hCG levels and the presence of the foetal ovum or its part in the tube. In 28 patients (23.5%) of the total number of 119 patients in the group, we observed an inflammatory infiltrate in the place of implantation. In these patients, the hCG levels were lower and in 17 of them (60.7%) we did not prove the presence of a foetal ovum or its parts. In women with GEU in their medical history, the AT-CMI positivity was established in 61.1% of the women 1 year after surgery, in 56.8% of the women 1-3 years after surgery and in 41.2% of the women 3 years after surgery. CONCLUSION: Ectopic pregnancy involves a pathological fetomaternal interface. The leucocytic infiltrate in the area of implantation may be of secondary character and may cause gradual destruction of the ectopically positioned product of conception. The results of our study indicate a possible participation of the increased AT-CMI in the destruction of the ectopically located trophoblast. Persisting anti-trophoblast immunity may influence the occurrence and course of further gravidities.

Cell Migration Inhibition↗

[Immunologically conditioned fertility disorders in men--experience of the immunobiological department of the Institute for Maternal and Child Care].

OBJECTIVE: To provide an overview of the results obtained from the more than ten-year systematic monitoring of the contribution of immunopathological mechanisms to the ethiopathogenesis of fertility disorders in men. DESIGN: A summarising retrospective study. SETTING: Mother and Child Care Institute, Prague. METHODS: The data source is a selected group of a total of 3,800 couples, who were examined in the Immunobiological Department (ID) of the Mother and Child Care Institute (MCCI) in Prague- -Podolí for fertility disorders in the past. From among the laboratory quantities, the following ones were systematically monitored: a) sperm parameters; b) cell-mediated immunity against spermatozoa; c) the presence of anti-spermatozoa auto-antibodies attached to spermatozoa; d) in a part of the clinical group, the serum concentrations of FSH, testosterone, SHBG and the free androgen index (FAI) were monitored. RESULTS: After selection was made according to defined criteria, the group comprised of a total of 1,680 men, of whom 49.4% were normozoospermic and 50.6% suffered from some form of seminal pathology. Increased cell-mediated immunity against spermatozoa was identified in 10.2% of fertile men, in 18.5% of normozoospermic men and in 66.3% of azoospermic men. In asthenozoospermic and teratozoospermic men, the increased cell-mediated immunity against spermatozoa was identified in 48.3% and 53.1% of them, respectively. The auto-antibodies attached to spermatozoa were identified in 3 out of every 42 fertile men (7%), while in asthenozoospermic men, it was a total of 21% (IgA antibodies) and 22% (IgG antibodies). As concerns the concentration of free androgens (FAI) in the serum, there was no difference among the individual subgroups of men. In oligoasthenozoospermic men, FSH was significantly higher on the average in comparison with normospermic men. CONCLUSION: The significantly higher incidence of increased cell-mediated immunity against spermatozoa in men with a pathological spermiogram in comparison with the control group (fertile men and normozoospermic men) indicates that cell-mediated immunity participates in the pathogenesis of seminal pathologies.

Androgens↗

Markers of inflammation in preeclampsia.

Advanced oxidation protein products (AOPP) represent terminal products of proteins exposure to free radicals. The aim of this study was to estimate the serum AOPP levels in preeclamptic patients together with ultrasensitive C-reactive protein and anticardiolipin antibodies (ACA) IgG and IgM. 21 women in the third trimester of pregnancy were included in the study--10 women with preeclampsia and 11 women with normal outcome of pregnancy. AOPP levels in preeclampsia were higher than those in normal pregnant women in the third trimester, but not statistically significantly. The comparison with AOPP levels in non-pregnant women has shown a significant increase (P<0.0001). CRP in preeclampsia was significantly increased in comparison with third trimester levels in normal pregnancy (P<0.001) as well as with non-pregnant women (P<0.0001). In preeclampsia, the ACA IgG levels were even significantly lower than in normal pregnant women in the same gestation age, but significantly higher than in non-pregnant women (P<0.001). No difference was found in ACA IgM in preeclampsia and normal third trimester pregnancy and non-pregnant women. A statistically significant negative correlation was found between AOPP and ACA IgG (r= - 0.708, P<0.05). The results indicate enhanced oxidative and inflammatory reaction of maternal organism to pregnancy, which is more pronounced in preeclampsia than in uncomplicated pregnancy.

Adult↗

[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↗