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V Toder

Publications and source records attributed to V Toder.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1989

Fetal demise associated with lupus anticoagulant: clinical features and results of treatment.

There are many reports in the literature associating lupus anticoagulant with fetal death. Successful pregnancies have been reported following suppression of the antibody by prednisone and the addition of antiaggregants and possibly anticoagulants. This report describes our experience treating such patients and the outcome of subsequent pregnancies. The results are less successful than the figures in the literature, 13 live births out of 27 pregnancies in 19 patients. This may be due to lupus anticoagulant being diagnosed as the cause for a wide variety of clinical presentations including habitual first trimester abortion, mid trimester fetal death, intrauterine growth retardation and placental dysfunction in the third trimester. Our experience shows that steroids and antiaggregants have a definite place in cases of second and third trimester fetal death and in cases of clinical systemic lupus erythematosus. However, lupus anticoagulant is one of a spectrum of autoantibodies whose pathophysiology has not been fully elucidated. It is questionable whether this regimen of treatment has a place in patients with no previous fetal loss or in cases of primary habitual abortion.

Adult↗
PubMed1989

Immunopotentiation and pregnancy loss.

To test the hypothesis that immunopotentiation of the maternal immune system is beneficial for the developing embryo, we examined (1) the effect of specific preimmunization with paternal leucocytes in women and BALB/c splenocytes in CBA/J x DBA/2J mice (which show increased % fetal resorption) and (2) the influence of non-specific potentiators such as complete Freund's adjuvant and thymus humoral factor on the abortion rate in CBA/J mothers. Subsequent pregnancy was successful in 76% of habitually aborting women after immunization with paternal leucocytes. Immunization of CBA/J mice with complete Freund's adjuvant (2 foot-pad injections) decreased the resorption rate (11.3% vs 34.9% without treatment). The effect was followed by a slight decrease of the L3H4-positive lymphocyte subpopulation in the spleen but not in the draining lymph nodes, as measured by flow cytometry analysis. The amount of Lyt-2 positive lymphocytes was not changed as a result of treatment. Thymus humoral factor did not influence the abortion rate in CBA/J females mated with DBA/2J male mice. Our results show that non-specific stimulation of the maternal immune system by complete Freund's adjuvant can improve reproductive success in allogeneic mice with increased pregnancy loss. The exact mechanism of this improvement is still unclear but it seems that systemic cellular mechanisms are not responsible for the effect.

Abortion, Habitual↗
PubMed1988

Immunologic aspects of IUD action.

Embryo implantation has been demonstrated to depend on specific lymphocyte populations within the uterine cavity. Intrauterine devices (IUD) exert their contraceptive action by prevention of embryo implantation via presently still unknown mechanisms. Therefore, mononuclear cell populations from mice uteri which either contained silastic or copper (Cu) IUD fragments or were sham-operated were evaluated, utilizing monoclonal antibodies against specific cell markers. Uterine horns, bearing IUD fragments, were significantly heavier than sham-operated horns. In Cu-IUD animals this effect extended even into the non-treated contralateral horn. The total number of lymphoid cells in IUD-bearing horns was significantly higher than in sham-operated horns. This observation was also made in non-treated contralateral Cu-IUD horns but not in contralateral horns of silastic-IUD-treated animals. Significant differences in percentages as well as absolute number of various lymphoid cell populations were noted between IUD-treated and sham-operated animals. Again, the effect was more pronounced in Cu-IUD-treated animals and extended in those animals into the contralateral horn. IUD-containing horns also demonstrated a significantly increased number of mast cells, with Cu-IUDs again resulting in a significantly more pronounced effect in both treated and contralateral horns. Sham-operated mice achieved a 67% pregnancy rate in both uterine horns. In contrast, IUD-treated animals demonstrated a significantly reduced pregnancy rate with silastic IUD fragments (15% and 30% for treated and contralateral horn, respectively) and a 0% pregnancy rate for Cu-IUD-treated animals (in either horn).

Animals↗
PubMed1987

Trophoblast does not cause the cytotoxic T lymphocyte generation due to the lack of ability to stimulate interleukin-2 production.

Trophoblast was demonstrated to be unable to cause the production of interleukin-2 (IL-2) by allogeneic splenocytes in vitro in two ways: 1) The addition of lymphocyte-trophoblast culture-supernatant (LTC-SN) did not stimulate the proliferation of IL-2 dependent cytotoxic T lymphocyte (CTL-L cells; 2) When responder cells were cultured with heat-treated splenocytes (usually no CTL generation) an increase of CTL formation could be seen in the presence of mixed lymphocyte culture-supernatant (MLC-SN) but not of SN from the cultures in which trophoblast cells served as stimulators. In parallel, the trophoblast cells were found to be very poor stimulators of alloreactive CTL. The addition of interleukin-2-enriched media resulted in a significant amplification of trophoblast-induced CTL generation. The resulting killing lymphocytes were capable of destroying the only specific targets, did not lyse syngeneic target cells, and could not be generated in the absence of allogeneic trophoblast. The incubation of these lymphocytes with anti-Thy 1.2 monoclonal antibody in the presence of complement eliminated their killing effect. Lack of class II antigenic determinants on the surface of trophoblast and/or local immunosuppression of IL-2 production by trophoblast cells seem to be responsible for nondelivery of helper factor, which is essential for CTL production.

Animals↗
PubMed1985

Natural killing (NK) potential of cord blood lymphocytes.

Different parameters of natural killing were evaluated in newborn cord lymphocytes using a 51Cr-release assay, a single cell cytotoxicity technique and an immuno-fluorescence method with HNK-1 monoclonal antibody. Cord blood lymphocytes expressed a positive natural killer (NK) activity although the level of this overall NK activity was lower than that of adult control (p less than 0.05). In neonates the number of cells bearing surface HNK-1 differentiation was very low (0.7 +/- 0.3). Contrary to this finding, newborns showed only a marginal decrease in the percentage of cells capable of recognizing and binding NK-sensitive target cells. However, the killing potential of these lymphocytes was impaired more profoundly (p less than 0.05) compared to adult controls. We conclude that in the neonate two distinct populations of effector cells participate in spontaneous killing. The first group is represented by classically defined NK cells (HNK-1 positive) while the second group represents. NK-like effector cells which lack the HNK-1 antigen. It seems that in newborns the latter type of cells represents the larger factor in spontaneous killing.

Adult↗