Fetal umbilical Doppler in a population of 541 high-risk pregnancies: prediction of perinatal mortality and morbidity. Doppler Study Group.

OBJECTIVE: To evaluate the usefulness of systematic umbilical Doppler in the assessment of high-risk pregnancies. METHOD: In a prospective multicentre study, a group of high-risk pregnancies (intrauterine growth retardation, hypertension during pregnancy, abnormal obstetric history) was systematically studied by Doppler exploration of the fetal umbilical artery between 28 and 34 weeks. All the details of pregnancy development to the first postnatal days were collected and analysed a posteriori. RESULTS: Three groups were formed according to Doppler results (Index S-D/S) A, index < 90th percentile (n = 458, 84.6%); B, index > or = 90th percentile and diastole over zero (n = 67, 12.4%); C, zero diastole (n = 16, 2.9%). There was a strong correlation between Doppler results and pregnancy development. Group C corresponded to a greatly altered prognosis (hypotrophy, < 3rd percentile in 69%; intrauterine deaths in 9/16). In group B, relative to group A, the prognosis was significantly altered (hypotrophy, 24% versus 6%, P < 0.01; prematurity rate, 25% versus 11%, P < 0.001) but these repercussions were not as severe as in group C. CONCLUSION: In high-risk pregnancies, fetal umbilical artery Doppler study is of interest for prognostic assessment. Normal results should provide temporary reassurance. Abnormal umbilical Doppler indicates that chronic suffering will occur or is onset in at least one-third of cases.

A murine monoclonal multireactive immunoglobulin kappa light chain.

N12.12 is a monoclonal immunoglobulin (Ig) kappa light chain (KLC) secreted by a B-cell hybridoma derived from spleen cells of a normal SJA mouse. No heavy chain was detected in the culture supernatant of this hybridoma using an enzyme immunoassay (EIA) and after polyacrylamide gel electrophoresis (SDS-PAGE) of the 35S-methionin biosynthetically labelled proteins secreted by the cells. It was shown that N12.12 KLC reacted with mouse actin, trinitrophenylated bovine serum albumin (TNP25-BSA) and weakly with bovine myoglobin. The binding of the N12.12 'monoclonal antibody' to mouse actin or to TNP25-BSA was inhibited specifically by both antigens with a dissociation constant (KD) for binding to mouse actin of 10(-7) M. The results indicate that a free KLC can bind both to mouse and to non-mouse molecules, thus exhibiting binding characteristics usually attributed to natural multireactive antibodies.

Thymic epithelium induces neither clonal deletion nor anergy to Mls 1a antigens.

Grafting of thymic anlagen from day-10 DBA/2 (H-2d; Mls-1a) embryos to newborn athymic BALB/c (H-2d; Mls-1b) mice leads to reconstitution of T cell populations in the recipients. Analysis of adult chimeras shows that their V beta T cell receptor (TcR) repertoires, particularly V beta 6 and V beta 8.1, do not significantly differ in most animals (10 out of 13) from those scored in control chimeras that received syngeneic thymic anlagen. In all cases analyzed, such Mls-1a-reactive T cells could be stimulated at levels comparable to control responses, both in vitro and in vivo. The few cases in which Mls-1a reactive V beta TcR were reduced seem to reflect the variability in TcR V beta repertoires found in this experimental system. In contrast, BALB/c mice, injected at birth with DBA/2 spleen cells show a marked, albeit variable, reduction in the frequencies of V beta 6- and V beta 8.1-bearing CD4+ T cells, and lower frequencies of Mls-1a-reactive T cells in limiting dilution analyses. It appears, however, that V beta 6- and V beta 8.1-bearing T cells remaining in these mice are functionally competent. We conclude that Mls-1 antigens are not expressed by thymic epithelium.

Transplantation tolerance correlates with high levels of T- and B-lymphocyte activity.

Mice tolerized (treated to make them tolerant) at birth to transplantation antigens by injection of semiallogeneic cells contain very high numbers of activated T and B lymphocytes in their spleen. Lymphoid hyperactivity correlates with the tolerant state: it is present only in animals accepting skin allografts. Tolerized mice that reject the allogeneic skin graft have approximately the same numbers of total and activated lymphocytes as normal mice. The high level of lymphocyte activation in tolerant mice persists for up to 1 year of age, although it declines with age, and is markedly increased by a secondary allograft. The magnitudes of both primary and secondary tolerant responses are significantly higher than the immunological response of a normal mouse rejecting the same type of allograft. These observations contradict concepts of clonal deletion or anergy as the basis of neonatally induced transplantation tolerance and may contribute additional approaches to experimentation and control of transplantation reactions.

Production and characterization of a mouse monoclonal antibody to the glycolipid asialo-GM1.

The glycosphingolipid asialo-GM1 (aGM1) is a true differentiation antigen of murine lymphoid cells. This glycolipid is highly immunogenic in the rabbit, but the antisera produced shows some cross reactivity with GM1, the naturally occurring sialylated derivative of aGM1. In the present study we examined the ability to raise anti-aGM1 antisera in the mouse. We compared the efficiency of several immunization methods in various strains of mice. The most effective procedure involved repeated intraperitoneal injections of aGM1-cholesterol rich particles in the NZB mouse. Hybrid B cell lines were generated by fusion of mouse myeloma cells with the splenocytes of an NZB mouse immunized with aGM1. The specificity of the antisera produced and of the monoclonal antibody secreted by one of these hybridomas (103HT30) was defined by ELISA and by immunostaining on thin layer chromatograms. The monoclonal antibody 103HT30 is an IgM. It reacted with aGM1 but not with any of the structurally-related ganglioside or neutral glycolipids tested. In particular, 103HT30 monoclonal antibody did not present any detectable cross-reactivity with GM1.

Genetics of susceptibility to oral tolerance to ovalbumin.

Inbred mouse strains vary widely in their susceptibility to the induction of tolerance following oral (intragastric) administration of ovalbumin. Marked differences were found between strains that form a congenic pair differing at the H-2 complex: C3H/HeJ (H-2k) and C3H.SW (H-2b)-which were very susceptible and resistant to tolerance induction, respectively. In contrast, no significant differences were found between A/J (H-2a) and A.BY (H-2b) congenics, which were both susceptible, nor among C57BL/10J congenics, which were uniformly resistant to tolerance induction. We conclude that H-2-linked genes determine tolerance susceptibility in conjunction with background genes.

Genetics of susceptibility to oral tolerance to ovalbumin

Inbred mouse strains vary widely in their susceptibility to the induction of tolerance following oral (intragastric) adminsitation of ovalbumin. Marked differences were found berween strains that form a congenic pair differing at the H-2 complex: C3H/HeJ (H-2K) and C3H.SW(H2b) - which were very susceptible and resitant to tolerance induction, respectively. In comtrast, no significant differences were found betwwwn a/J(H-2a) and A.BY (H-2b) congenics, which were both susceptible, nor among C57BL/10J congenics, which were uniformly resitant to tolerance induction. We conclude that H-2-linked genes determine tolerance susceptibility in conjunction with background genes