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V Toder

Publications and source records attributed to V Toder.

At least 19 recordsLinked to original sources
PubMed1995

Pregnancy-associated effect on mouse thymocytes in vitro.

Thymic involution during pregnancy is a phenomenon which has been described for a long time in various mammalian species but its significance for the success of pregnancy in not yet known. Consequently, we have studied the effect of placental cells on functional activity and cell surface antigen expression of thymocytes in combination with the thymic stroma. Trophoblast cells inhibited almost completely the proliferative response of thymocytes whether or not combined with the thymic stroma. Decidual cells were also found to have an inhibitory effect on thymocytes proliferation while their combination with the thymic stroma decreased the thymocyte proliferation rate almost completely. Both decidual and trophoblast explants in combination with the thymic stroma increased CSF production by the thymocytes while inhibiting IL-6 production. Also, both trophoblast and decidual cells caused no significant changes in the expression of Thy-1, CD5, CD4, CD8, CD3, CD25, CD44, and L-selectin by the thymocytes. Comparable results were obtained for lymph node cells in terms of both proliferation and cell surface antigen expression, except for a trophoblast-dependent decrease in L-selectin expression. These results suggest a possible role for placental cells in immunoregulation of functional activity of thymocytes, which might represent one of the mechanisms mediating pregnancy-associated thymic involution in vivo. However, no correlation between thymocytes functional activities and changes in their cell surface antigen expression could be established.

Animals↗
PubMed1994

MHC-associated immunopotentiation affects the embryo response to teratogens.

The present study was performed to evaluate whether the effect of environmental teratogens can be modified by maternal immunostimulation. Two chemicals, cyclophosphamide (CP) and 2,3-quinoxalinedimetanol,1,4-dioxide (QD) were used as the reference teratogens (RT). The response to these RT was investigated in two animal models: (i) primigravid C57Bl/6 mice who underwent intrauterine immunization with allogeneic paternal (CBA/J), third-party (BALB/c) or syngeneic male splenocytes 21 days before mating; (ii) C57Bl/6 and CBA/J mice who were treated with RT during the second pregnancy only, after a different mating combination (syngeneic or allogeneic) in the first and the second pregnancy. Different doses of CP and QD were injected on days 12 and 9 of pregnancy, respectively. On day 19 of pregnancy implantation sites, resorptions, live and dead fetuses were recorded and live fetuses were examined for external and internal malformations with methods routinely used in teratological study. It was shown that intrauterine immunopotentiation with allogeneic paternal splenocytes clearly enhances the tolerance of F1 embryos to RT. Thus, in CP-treated females the resorption rate and the proportion of malformed fetuses were significantly reduced. It was followed by an almost two-fold increase in fetal weight. The protective effect of such immunization in QD-treated females was manifested as a dramatic decrease of the proportion of malformed fetuses and the resorption rate. Syngeneic splenocytes could not significantly influence an embryo's sensitivity to RT. The response to RT was also significantly weaker in the second pregnancy of female mice mated twice allogeneically than that observed in allogeneically mated primigravid mice. These results show that the embryo's response to environmental teratogens may be influenced by fetomaternal immune interactions.

Abnormalities, Drug-Induced↗
PubMed1993

Congenital malformations after immunotherapy for habitual abortion: is there an increase?

The risk of congenital malformations as assessed in infants born to women who underwent immunotherapy for habitual abortion. One hundred and eighty women were immunized with paternal mononuclear cells and 85 were not. Of 135 pregnancies in immunized patients, 27 (20%) were miscarriages, and 4 of the remaining 108 had congenital malformations. Two (encephalocele and common AV canal) were diagnosed in the 20th and 21st week of gestation. A case of esophageal atresia and Fallot's tetralogy were diagnosed at birth. Of 65 pregnancies in the non-immunized group 38 (58.5%) were miscarriages, and of the remaining 27, 1 case of Down's syndrome occurred. In a subgroup of 7 habitually aborting couples with parental balanced chromosomal anomalies, the balanced translocation was transferred to the infant in 1 case. No other congenital anomalies were found in either group. Consequently, these anomalies are probably not the result of abnormal pregnancies retained as a result of immunization.

Abortion, Habitual↗
PubMed1991

Induction of anti-phospholipid syndrome in naive mice with mouse lupus monoclonal and human polyclonal anti-cardiolipin antibodies.

The primary anti-phospholipid syndrome is characterized by recurrent venous and arterial thromboembolic phenomena, recurrent fetal loss, thrombocytopenia, and serological evidence of anti-cardiolipin (aCL) antibodies or/and the presence of lupus anticoagulant (prolonged activated partial thromboplastin time). The exact role of aCL antibodies in pathogenesis is not clear and the mechanism by which the antibodies may induce the various manifestations is unknown. In the current study we evaluated the effect of passive transfer of aCL antibodies (to the tail vein of naive mice) on fecundity, fetal loss (fetal resorption), and the weight of embryos and placentae. Two types of aCL antibodies were employed: (i) mouse monoclonal aCL antibodies derived from a BALB/c mouse in which experimental systemic lupus erythematosus was induced by a pathogenic idiotype (idiotype 16/6) of anti-DNA antibodies and (ii) polyclonal IgG and IgM aCL antibodies derived from serum of a patient with primary anti-phospholipid syndrome. After infusion of either antibody (10 micrograms per mouse) we could demonstrate lower fecundity rate, increased resorption index of embryos (equivalent to recurrent fetal loss), lower number of embryos per pregnancy, and lower mean weights of embryos and placentae in comparison to mice infused with appropriate control immunoglobulins. We conclude that the aCL antibodies may have direct effects on fecundity and on the outcome of pregnancy.

Animals↗
PubMed1991

Immunopotentiation reverses the embryotoxic effect of serum from women with pregnancy loss.

OBJECTIVE: To assess the effect of sera of women with habitual abortions (AB) on attachment and spreading of mouse blastocysts in vitro. DESIGN: Expansion, attachment, and spreading were the mouse blastocyst parameters utilized. Deoxyribonucleic acid (DNA) synthesis and cell markers expression were also assayed by autoradiography analysis and the indirect immunofluorescent technique. SETTING: Sera were drawn from patients attending a habitual AB clinic in a tertiary care university hospital. PARTICIPANTS: Thirty-nine serum samples were drawn from habitually aborting women and the effect compared with 17 control AB sera. INTERVENTION: Habitually aborting women were immunized with paternal leucocytes; 18 post-immunization sera were also assessed. OUTCOME AND RESULTS: After 48 hours, there was delayed attachment and spreading (4% of test blastocysts spread as compared with 50.5% of controls). This was more profound after 72 hours culture (7.5% spread as compared with 72.8% of controls). Experimental sera were capable of reducing DNA synthesis, cytokeratin, fibronectin, or placental alkaline phosphatase expression by blastocyst cells. Leucocyte immunization of women with habitual ABs, clearly reversed the embryotoxic effect of the sera and enhanced cell markers expression. CONCLUSIONS: These data suggest that immunopotentiation may improve blastocyst survival in utero.

Abortion, Habitual↗
PubMed1991

Mouse model for the treatment of immune pregnancy loss.

Spontaneous abortions can be associated with preimplantation embryo loss, implantation problems and a variety of postimplantation pregnancy failures. The long list of possible causes for the postimplantation pregnancy loss includes, among others, genetic abnormalities in fetus, anatomical abnormalities of the uterus, endocrinological insufficiency, and microbiological problems. However, more than 50% of recurrent miscarriages still have no recognized causes. The concept that many such abortions may be immunologically mediated has gained increasing support over the years. Moreover, immunization of such women with husband's or third party leukocytes has resulted in more than 70% of subsequent pregnancies resulting in live births. Since neither the mechanisms leading to pregnancy loss nor the success of immunotherapy are clear, the set-up of animal models for recurrent abortions would be of supreme significance. Our recent data show that immunopotentiation of maternal immune system by Complete Freund Adjuvant significantly improves pregnancy rate in CBA x DBA/2 mouse combination with high percentage of fetal resorptions. This effect is followed by decrease of IL 2 production in spleen; increase of MAC 1-positive cells at placenta; amplification of suppressive activity of local and systemic lymphocytes and by reverse of embryotoxic effect of maternal serum. Data obtained in this model seems to be valuable in substantiation of rationale for nonspecific immunotherapy of human abortions.

Abortion, Spontaneous↗
PubMed1990

Selection of patients with habitual abortion for paternal leucocyte immunization.

After potentiation of the immune response in habitual aborters 75-85% of subsequent pregnancies are claimed to result in healthy term infants. However, all publications to date have either been based on the authors concept of the immune processes involved or an attempt to demonstrate the efficacy of treatment either empirically or by matched trials. As immunization is coming into wider clinical use, it is necessary to determine which patients will benefit from this form of treatment. This paper presents our experience with paternal leucocyte immunization over the period 1985-1988. 207 patients were classified on a clinical basis and by immunological testing. 143 patients have been immunised, 129 pregnancies have occurred in 108 patients. The vast majority of our patients have recurrent missed abortions. Only six women habitually aborted live fetuses. Two had subsequent live births. Secondary aborters seem to do well in subsequent pregnancies, whether immunized or not. The patient most likely to benefit from immunization is the Primary missed aborter who does not possess antipaternal antibody (APCA), but is induced to produce APCA by immunization. Using these criteria, 75% success rates are observed in the subsequent pregnancy. This success rate is irrespective of HLA antigen sharing or in-vitro mixed lymphocyte reactivity.

Abortion, Habitual↗
PubMed1990

Nonspecific immunopotentiators and pregnancy loss: complete Freund adjuvant reverses high fetal resorption rate in CBA x DBA/2 mouse combination.

CBA/J female mice mated with DBA/2J males show a high incidence of fetal resorptions. This paper presents data demonstrating that nonspecific immunopotentiation by complete Freund adjuvant (CFA) reversed pregnancy loss in CBA/J mothers. Immunization of more than 70 CBA/J females mated with DBA/2J males with CFA reduced the incidence of fetal resorption from 27.3 +/- 1.9 to 7.9 +/- 1.5%. The injection of Thymus Humoral Factor known to be a potent T cell stimulator did not reduce the number of fetal resorptions. The route of CFA distribution was found to be important--only foot pad injections were effective in fetal protection, whereas i.p. treatment did not reduce fetal resorptions. Fetal protection could be transferred by splenocytes of CFA-injected CBA/J mothers (9.6 +/- 5.0% fetal resorptions). Sera from treated CBA/J mice could not cause such an effect (17.6 +/- 4.6 vs. 21.3 +/- 6.1 in control animals). Thus, stimulation of the maternal immune system by nonspecific immunopotentiators can improve reproductive performance of this mouse combination which has an increased rate of pregnancy loss. Possible mechanisms of this fetal protection are discussed.

Animals↗
PubMed1990

Immunization by paternal leukocytes for prevention of primary habitual abortion: results of a matched controlled trial.

Habitual abortion is a difficult clinical problem, as no cause can be found for abortion in over 50% of patients. At the habitual abortion clinic of the Sheba Medical Center, immunological activity is tested and patients who are considered suitable are offered immunopotentiation with paternal leukocytes. Patients are only treated if they have no other cause for habitual abortion, no lupus anticoagulant and no antipaternal complement-dependent antibodies (APCA). Immunization is thought to potentiate the maternal immune response to paternal antigens encountered on the trophoblast. The production of APCA antibody indicates that an immune response has occurred. Of the 156 patients so far immunized, 109 have developed these antibodies. To date, 79 of these 156 patients have become pregnant. Sixty-seven patients (with 3-12 miscarriages each) belong to the antibody-positive group. Sixty-four of the 89 subsequent pregnancies have been carried past their previous dates of abortion. Forty-seven live births have occurred. By contrast, 12 patients have been pregnant in the antibody-negative group, of the 16 subsequent pregnancies only 6 were successful. A control group is available for comparison. This consists of patients suitable for immunization, but not immunized. Of these patients, only 11 of 30 pregnancies have been carried to term.

Abortion, Habitual↗