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Biomedical subjects

N W Klein

Publications and source records attributed to N W Klein.

47 records · Page 3Linked to original sources
PubMed1969

The differential sensitivity of cultured chick mesodermal cells to actinomycin D.

Cells were isolated from the somite mesoderm and from the unsegmented (presomite) mesoderm of early chick embryos and exposed to actinomycin D in single cell culture. Actinomycin D inhibited proliferation in cell cultures derived from the unsegmented mesoderm, although the same concentrations of this antibiotic did not inhibit cultures derived from the somite mesoderm. This differential sensitivity parallels the regionally specific necrosis and degeneration observed in the unsegmented mesoderm of intact chick embryos exposed to actinomycin D. In culture, both cell types exhibited approximately the same permeability to labeled actinomycin D and showed comparable inhibition of RNA, DNA, and protein syntheses in the presence of the antibiotic. However, freshly isolated mesodermal cells from the somite region had a higher content of RNA than did cells from the unsegmented region, and the somite cells maintained a higher rate of macromolecular synthesis in untreated cultures.

Animals↗
PubMedDate not supplied

Role of laminin autoantibodies on the embryo toxicity of sera from mercuric chloride treated brown Norway rats.

In previous studies, antilaminin antibodies were found to be toxic to cultured rat embryos. In order to extend these studies, Brown Norway rats were treated with mercuric chloride, which led to the production of laminin autoantibodies. Sera samples from brown Norway rats treated with mercuric chloride were found to be teratogenic as well as lethal to cultured rat embryos. This embryotoxicity was not associated with sera mercury levels, but was related to the levels of antilaminin antibodies in sera. Affinity purified laminin antibodies from these mercuric chloride treated Brown Norway rats, when added to control sera, were found to be teratogenic but not lethal. These antibodies were found to bind to the laminin sequences IKVAV (A chain) and YIGSR (B1 chain), but not RGD (A chain) or YD (B1 chain). These observations suggested the possibility that an environmental pollutant such as mercury could cause the formation of embryotoxic autoantibodies that could persist in the body as embryotoxic factors for extended periods of time.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Identification of a teratogenic drug-protein complex in sera of phenytoin-treated monkeys.

Whole rat embryos were cultured for 48 h on sera drawn from monkeys before and 10 h after phenytoin gavage (275 mg/kg body weight). Sera from treated monkeys caused exencephaly, anophthalmia, microcephaly, and incomplete ventral curvature when used as culture media, whereas sera drawn from the same monkeys before treatment supported normal embryonic development. To identify the cause of serum teratogenicity, isolated constituents of teratogenic sera were added to nonteratogenic sera for testing by embryo culture. Serum extracts containing free phenytoin and its free metabolites were not teratogenic. Teratogenicity was found associated with serum proteins. Using polyacrylamide gel electrophoresis (PAGE) and an antibody that recognized phenytoin and its metabolites, we were able to demonstrate that phenytoin was bound to a protein of 80,000 daltons. Addition of this same antibody to teratogenic sera from dosed monkeys improved the development of cultured embryos and provided additional support for this complex as the proximal teratogen. Use of the antibody to follow the uptake and distribution of phenytoin in cultured embryos suggested that only the phenytoin-protein complex (and not phenytoin itself) was able to pass through the yolk sac and reach the tissues of the embryo proper. These results suggested that a drug-protein complex may serve to transport drugs from their site of activation in the maternal liver to the developing embryo.

Abnormalities, Drug-Induced↗