Antepartum fetal monitoring in insulin-dependent diabetic pregnancies.

In order to minimize unexplained stillbirths in insulin-dependent diabetic pregnancies, fetal well-being was assessed by antepartum monitoring while development of pulmonary maturity was awaited. Antepartum monitoring consisted of outpatient nonstress tests beginning at 32 weeks' gestation. Fetuses with nonreactive nonstress tests were further evaluated by contraction stress tests and were delivered if tests were positive. With use of this system there were no unexplained stillbirths during management of 119 insulin-dependent diabetic pregnancies. Of 14 infants delivered because of positive contraction stress tests, six were found to have major disorders; the other eight had no major residual neonatal morbidity. Thus this system of antepartum fetal surveillance: eliminated unexplained stillbirths, identified a subgroup of insulin-dependent diabetic pregnancies with a high rate of major fetal abnormalities, and allowed for identification and subsequent timely delivery of the other distressed fetuses that were at a high risk of neonatal morbidity and/or mortality, such that potential long-term adverse outcomes were avoided.

Sequence comparison of rat liver phenylalanine hydroxylase and its cDNA clones.

Classical phenylketonuria, an inborn error in metabolism, is caused by a deficiency of the hepatic enzyme phenylalanine hydroxylase. The identification of putative cDNA clones coding for rat liver phenylalanine hydroxylase by hybrid-selected translation has previously been reported [Robson, K. J., Chandra, T., MacGillivray, R. T. A., & Woo, S. L. C. (1982) Proc. Natl. Acad. Sci. U.S.A. 79, 4701-4705]. The authenticity of the clones, however, could not be definitively ascertained at the time because of a lack of amino acid sequence data of the enzyme in the literature. Purified rat liver phenylalanine hydroxylase was subjected to cyanogen bromide treatment, and the resulting fragments were used for N-terminal amino acid sequence analysis. The partial amino acid sequence was then compared to that deduced from an open reading frame in the nucleotide sequence of the cDNA clones. A perfect match of 17 amino acid residues was found between the two sequences following a unique methionine codon present in the nucleotide sequence, thereby providing unambiguous evidence for the identity of the rat liver phenylalanine hydroxylase cDNA clones.

Congenital abnormalities induced by heterologous antisera directed against rat kidney glycoproteins isolated by concanavalin A affinity chromatography.

It has been well established that heterologous antisera against whole rat kidney homogenate when injected into pregnant rats during the embryonic organogenetic period may induce abnormal embryonic development. Attempts were made to isolate the active components from soluble rat kidney extract by ammonium sulfate precipitation, anion-exchange chromatography, and concanavalin A-Sepharose 4B affinity chromatography. The glycoproteins isolated were capable of stimulating the production of potent rabbit antisera. When injected ip into the 9th day pregnant rats, these antisera induced embryonic death, congenital abnormalities, and fetal growth retardation. Eighty-four surviving fetuses were examined, all of them were malformed. The most frequently observed congenital defects were anophthalmia and microphthalmia. Attempts were made to analyze the glycoprotein fraction by discontinuous and sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. The results indicate that the glycoproteins were of high molecular weight and could be dissociated by SDS into a multitude of molecules or subunits. Although double immunodiffusion indicated that there were one major and two minor antigens in the glycoprotein fraction, attempts to identify the antigens as to their size by analytical gel electrophoresis have not been successful. Electron microscopic study seemed to suggest that the glycoproteins might tend to aggregate to form particulates. The underlying mechanism whereby the antisera to these glycoproteins induce abnormal embryonic development is not understood. The hypotheses to explain the possible sites of teratogenic antibody interaction are discussed.