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Biomedical subjects

C J Epstein

Publications and source records attributed to C J Epstein.

At least 217 records · Page 12Linked to original sources
PubMed1980

Genes coding for sensitivity to interferon (IfRec) and soluble superoxide dismutase (SOD-1) are linked in mouse and man and map to mouse chromosome 16.

By using 12 hamster-mouse hybrids segregating a mouse T(16;17)Bnr Robertsonian translocation chromosome in conjunction with 10 similar hybrids segregating normal mouse chromosomes, we have shown that the loci that control cellular sensitivity to interferon (IfRec) and code for the soluble enzyme superoxide dismutase (SOD-1) (superoxide:superoxide oxidoreductase; EC 1.15.1.1) are syntenic in the mouse and map to mouse chromosome 16. IfRec and SOD-1 are also syntenic in man. They have previously been assigned to the distal segment of the long arm of human chromosome 21, trisomy for which causes Down syndrome. Because both IfRec and SOD-1 map to mouse chromosome 16, it will now be possible to use mice trisomic for this chromosome to determine whether certain aspects of the Down syndrome phenotype in man are caused by an altered dosage of IfRec and SOD-1.

Animals↗
PubMed1980

Synthesis of interferon-induced polypeptides in normal and chromosome 21-aneuploid human fibroblasts: relationship to relative sensitivities in antiviral assays.

Localization of the gene for the species specific response to interferon (IFRC) to human chromosome 21 has stimulated interest in the effect of aneuploidy for chromosome 21 on cell sensitivity to interferon. Previous reports have shown that the relative sensitivities of trisomy 21, diploid and monosomy 21 human fibroblasts as measured in an antiviral assay are greater than the ratio 0.67 : 1.0 : 2 predicted on the basis of gene dosage for IFRC. As an alternative test for sensitivity, we have investigated the synthesis of interferon-induced polypeptides visualized by 2-dimensional gel electrophoresis and autoradiography. Of 10 such polypeptides identified, 3 were measured quantitatively in 2 diploid, 2 trisomic, and one monosomic fibroblast strains. In contrast to the antiviral response, the relative responses in this test correspond closely to expected gene dosage relationships over a range of interferon concentrations from 0.5 to 5000 units/ml. These results are compatible with the conclusion that the number of IFRC gene products (presumed to be the interferon receptor) per cell is proportional to the number of IFRC genes. Thus, the amplified effect of aneuploidy as measured in the antiviral response appears to result from some step subsequent to synthesis of interferon receptors and formation of interferon-receptor complexes.

Autoradiography↗
PubMed1980

Expression of H-Y antigen on preimplantation mouse embryos.

The expression of H-Y antigen on preimplantation mouse embryos has been studied by complement dependent cytotoxicity. Embryos at the 8-cell stage were exposed to anti-H-Y and complement and then scored for cell death. Overall, half of the treated embryos were killed, retarded, or contained dead cells. Of those embryos which were not affected by anti-H-Y, 92% were female. In control experiments, neither normal serum plus complement nor complement alone had any specific effect on male embryos. It is concluded, therefore, that the H-Y antigen is present on preimplantation mouse embryos.

Animals↗
PubMed1979

Prenatal genetic diagnosis in 3000 amniocenteses.

We analyzed 3000 consecutive amniocenteses for prenatal diagnosis to assess the frequency of abnormalities, safety of the procedure, technical and interpretive difficulties and overall diagnostic accuracy. Chromosomal abnormalities were detected in 2.4 per cent of the 2404 pregnancies tested because of advanced maternal age (greater than or equal to 35 years), in 1.2 per cent of 240 monitored because of prior trisomy 21 and in 9.1 per cent of 55 examined for other cytogenetic indications. Mosaicism was detected in 0.4 per cent, and unexpected translocations in 0.4 per cent. Amniotic fluid was obtained on the first attempt in 99.3 per cent of the last 1000 cases, and cultures established from 99.7 per cent of patients attending our clinic. The fluid was discolored in 1.2 per cent of patients, a quarter of whom had missed abortions. The rate of spontaneous abortion after amniocentesis was 1.5 per cent. There were 14 diagnostic errors, six serious enough to affect the outcome of pregnancy. The karyotyping error rate was 0.07 per cent. We conclude that prenatal diagnosis is safe, highly reliable and extremely accurate.

Abortion, Spontaneous↗
PubMed1979

Manipulation of myogenesis in vitro: reversible inhibition by DMSO.

A system has been developed for the detailed analysis of the transition from proliferative myoblast to differentiated muscle cell. Dimethylsulfoxide (DMSO) prevents the terminal differentiation of L8 myoblasts in vitro, and its effect is reversible. DMSO (2%) inhibits the fusion of myoblasts to form multinucleate myotubes, the normal increases in activity of creatine phosphokinase (CPK) and acetylcholinesterase, and the synthesis of alpha-actin and acetylcholine receptor protein. Upon removal of DMSO from the medium, a lag precedes the onset of differentiation. The potential to inhibit muscle differentiation reversibly is not specific to DMSO, but is shared by a number of compounds, including dimethylformamide, hexamethylbisacetamide and butyric acid, all potent inducers of gene expression in Friend erythroleukemia cells. L8 cells routinely cease DNA synthesis and initiate fusion and muscle protein synthesis once they are confluent. In the presence of DMSO, however, nearly all cells continue DNA synthesis, even several days after reaching confluence. Protein synthetic patterns of DMSO-inhibited cells are almost indistinguishable from those of untreated myoblasts and distinct from differentiated myotubes. It appears that cells exposed to DMSO are locked indefinitely in a proliferative myoblast stage of development and are unable to enter the Go phase of the cell cycle necessary for initiation of differentiation. DMSO coordinately inhibits all the differentiative parameters measured. In contrast, cytochalasin B uncouples normally linked differentiative events so that fusion is inhibited while muscle-specific protein synthesis proceeds. DMSO has similar effects on both cytochalasin B-treated and fusing control cultures, suggesting that its primary effect is exerted not at the level of fusion but earlier in the differentiative time-table. Once fusion and the synthesis of muscle-specific proteins are well under way, the addition of DMSO is ineffective and differentiation continues in its presence. The potential to manipulate muscle gene expression in vitro makes this system particularly useful for the detailed analysis of the processes involved in the transition to the differentiated state and for determining the linkage of developmental events.

Actins↗
PubMed1979

The effect of trisomy 21 on the patterns of polypeptide synthesis in human fibroblasts.

In addition to direct gene dosage effects, the deleterious phenotypic consequences of aneuploidy may result from secondary regulatory effects on the production and degradation of gene products coded for by other chromosomes. In an initial test of the hypothesis that extensive secondary effects play an important role in the phenotypic consequences of aneuploidy, we have used two-dimensional gel electrophoresis with radioautography to look for such secondary effects among the polypeptides synthesized by human fibroblasts grown in vitro. The polypeptide patterns of fibroblast strains from four trisomy 21 subjects and one trisomy 21/normal mosaic were compared to those from five matched normal subjects. Of approximately 850 polypeptides visualized, only four show a pattern of variation which may be related to trisomy 21. Additional differences in polypeptide concentrations were found among the strains, attributable to genetic heterogeneity between donor individuals and differences in tissue of origin. These results indicate that, at least in fibroblasts in vitro, trisomy 21 does not cause major regulatory changes in the rates of production and degradation of a large number of polypeptides.

Adult↗
PubMed1979

Partial trisomy for the distal long arm of chromosome 5 (region q34 leads to qter). A new clinically recognizable syndrome.

This report describes a family in which eight individuals in three generations had mental retardation in association with a characteristic pattern of clinical problems and physical abnormalities including short stature, eczema, hernias, delayed puberty, dysmorphic facies and digital anomalies. The family history was consistent with a chromosomal rearrangement with transmission through balanced carriers. Routine ASG banding studies showed extra chromosomal material on a chromosome 16 but failed to demonstrate any differences between the affected individuals and the presumed carriers. However, subsequent studies utilizing trypsin banding and microspectrophotometry of individual chromosomes demonstrated that the affected individuals were partially trisomic for the distal band of the long arm of chromosome 5 and that 0.273 units of a chromosome 5 were translocated to chromosome 16. This definitive cytogenetic diagnosis permitted accurate prenatal diagnosis to be carried out on the fetus of a balanced carrier female. The application of these techniques to previously obscure familial dysmorphic syndromes is recommended.

Abnormalities, Multiple↗