Rat embryo development on human sera is related to numbers of previous spontaneous abortions and nutritional factors.

OBJECTIVES: The objectives were to determine (1) if sera from women with histories of spontaneous abortions were teratogenic to cultured embryos more often than were sera of nonaborters, (2) if the teratogenicity could be corrected by adding nutrients to the sera, and (3) if these findings were relevant to reproductive outcomes. STUDY DESIGN: Rat embryos were cultured for 48 hours on sera from 102 subjects who had experienced spontaneous abortions. Samples from 48 were retested with nutrients added and 10 took dietary supplements, were again tested with embryo cultures, and reported on their pregnancy outcomes. RESULTS: The frequencies of teratogenic sera increased with numbers of spontaneous abortions (0 to > or = 5) in a manner that did not deviate from linearity (27% to 89%) (chi 2 p > 0.957). Nutrient supplements were added to 48 samples, and 40 were corrected and 10 subjects were given dietary supplement. Sera from six showed improved embryo cultures, and these women completed their pregnancies. CONCLUSIONS: Rat embryo cultures may provide unique insights into the causes and treatment of spontaneous abortions.

Extracorporeal shock wave lithotripsy for patients with calcified ipsilateral renal arterial or abdominal aortic aneurysms.

A total of 4 patients with renal or upper ureteral calculi associated with ipsilateral calcified renal arterial or abdominal aortic aneurysms underwent extracorporeal shock wave lithotripsy. One patient with a renal artery aneurysm had a solitary kidney. Linear distance from the calcified aneurysm to the stone, calculated by computerized and plain tomography, ranged between 4.6 and 6.5 cm. (mean 5.3). Treatment was accomplished on an unmodified Dornier HM3 lithotriptor using 900 to 2,400 shock waves (mean 1,575) at 18 kv. There were no complications of treatment and all 4 patients were discharged from the hospital within 24 hours, at which time radiographic examination revealed excellent stone comminution without change in the calcified aneurysm. With followup as long as 30 months, no adverse effects of therapy have become evident. We conclude that the presence of an ipsilateral calcified aneurysm may not necessarily preclude treatment of renal or upper ureteral calculi with extracorporeal shock wave lithotripsy, although further studies are required to help define the potential limits of such therapy in this setting.

Autoantibodies to laminin and other basement membrane proteins in sera from monkeys with histories of reproductive failure identified by cultures of whole rat embryos.

Head-fold-stage rat embryos cultured on sera taken from monkeys with histories of reproductive failure had an abnormality frequency of 97% compared with only 7% on sera taken from monkeys with excellent reproductive histories. For a group of these poor reproducers, the toxicity of their sera was associated with the immunoglobulin G (IgG) fraction. These IgG fractions bound to Reichert's membrane and other basement membranes of the embryo. For one monkey, the IgG specifically reacted with a 41 kDa polypeptide of Reichert's membrane, while for two others binding was to laminin, type IV collagen, and several other minor polypeptides of Reichert's membrane. For serum from one monkey, the toxicity to cultured rat embryos was eliminated by absorption with laminin but not type IV collagen.

Immune complexes bind to cultured rat glomerular mesangial cells to stimulate superoxide release. Evidence for an Fc receptor.

Contractile mesangial cells (MC) possess a number of macrophage-like characteristics, including oxygen radical generation. We suggest that under certain conditions MC may serve as immune effector cells in glomerulonephritis. Immune complex (IC) deposits are a hallmark of glomerulonephritis. Because IC elicit oxygen radicals from other cell types and because oxygen radicals can induce glomerular injury, we measured release of O2- by cultured rat MC in response to IC and, in separate experiments, the binding of IC to MC. Soluble and insoluble IC markedly stimulated dose- and time-dependent, saturable O2- release. Specific antibody (Ab) alone or mixtures of nonimmune Ab and antigen had no significant effect. IC-induced O2- release was not affected by cytochalasin B, an inhibitor of phagocytosis. Binding studies with radioiodinated IC demonstrated specific binding with an affinity of 1.56 X 10(6) M-1 and 1.02 X 10(5) receptors per cell. Both binding and O2- release required the Fc region of Ab. IC formed with F(ab')2 fragments did not bind specifically to or stimulate O2- release by MC. Cultured cells from rats depleted of bone marrow-derived phagocytes by irradiation produced amounts of O2- similar to cells from normal rats. These results provide evidence that IC affect the biology of the contractile glomerular MC in a manner that is dependent on the Fc region of Ab and suggest that MC structure and function may be altered at sites of injury.

Uptake and distribution of exogenous serum proteins in the cultured rat embryo.

Head fold stage rat embryos were cultured on a medium consisting of adult rat serum for 48 hr. During the final 10 or 20 hr of culture [35S]-methionine was added to the medium. Sera from visceral yolk sac blood vessels, exocoelomic cavity fluid, and amniotic sac fluid were analyzed by SDS-polyacrylamide gel electrophoresis followed by Amido Black staining and fluorography. Amido Black staining showed bands in all three embryonic fluid compartments which migrated at rates comparable to transferrin, alpha-fetoprotein, albumin, IgG, and hemoglobin. Fluorography, however, showed that radioactivity was restricted to alpha-fetoprotein, IgG, and hemoglobin. This suggested that at least some transferrin and albumin were transferred intact from the exogenous medium to the embryonic fluid compartments.