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Biomedical subjects

L B Epstein

Publications and source records attributed to L B Epstein.

At least 73 records · Page 4Linked 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

Sensitivity of human ovarian carcinoma cells to interferon and other antitumor agents as assessed by an in vitro semi-solid agar technique.

To determine the sensitivity in vitro of human ovarian carcinoma cells to the antiproliferative effects of human leukocyte interferon, 18 samples of ascitic fluid from 15 affected patients were cultured in semi-solid agar by the technique of Hamburger and Salmon. Cultures were examined at weekly intervals after initiation and the number and size of each tumor colony recorded. Growth as defined by increase in total tumor colony number with time was obtained in 45% of the samples, or 53% of the patients, or 67% of the ascitic fluid samples with tumor cells demonstrated by Pap smear. No growth occurred in samples from recently treated patients or in samples devoid of tumor cells as assessed by Pap smear. Response to interferon directly incorporated into the agar culture system or preincubated with cells prior to their inclusion in culture was defined as reduction in total colony number by greater than or equal to 50% and partial response by greater than or equal to 25% reduction. The response rate for samples, The nontreated controls of which showed evidence of growth, was 71%, and that of samples that contained tumor colonies with no increase in growth during the culture period was 75%. Sensitivity to interferon was not related to the histology or grade of the tumor or to the stage of the disease. In general the responsiveness of the tumor cells to interferon ran parallel to the overall responsiveness to a variety of other chemotherapeutic agents. As this culture system has been proven by other investigators to be predictive of in vivo resistance to antitumor drugs with considerable accuracy and also to be predictive of in vivo response to a lesser degree, it will be important to determine whether similar relationships between in vitro and in vivo sensitivity obtain for interferon.

Adult↗
PubMed1980

Further experience in testing the sensitivity of human ovarian carcinoma cells to interferon in an in vitro semisolid agar culture system: comparison of solid and ascitic forms of the tumor.

We studied the in vitro growth characteristics of 10 solid-tumor samples of patients with ovarian carcinoma using a semisolid agar culture technique. Tumor cell colonies were observed in 8 of 10 samples, but sufficient number of tumor colonies to evaluate the effects of interferon and other antitumor agents were obtained in only four samples. As compared with cell suspensions prepared from ascitic fluid samples, solid-tumor samples had markedly lower viability, 39% vs 89%, and had more tumor cells, 81% vs 28%. Also, whereas the maximum increase in tumor-colony number occurred during the first week of growth in both solid- and ascitic-fluid-derived samples grown concurrently from the same donors, increase in tumor colony number was sustained for longer periods in ascitic-fluid-derived cultures. The ascitic-fluid-derived tumor colonies were more sensitive to the antiproliferative effects of interferon than colonies derived from solid-tumors. At a concentration of 300 units/ml incorporated into the agar for the duration of the culture, three of four ascitic fluid samples showed a reduction in tumor colony number by greater than or equal to 25%, whereas none of the solid-tumor samples were affected by the interferon to that degree. In contrast, solid-tumor samples showed greater response to cis platinum and Adriamycin than did ascitic-fluid-derived cultures. Such studies and observations are critical in designing clinical trials for the use of interferon in the treatment of malignancy and the judicious selection of patients and route of administration most likely to provide optimal results, especially in view of present critical shortages in availability of interferon.

Adult↗
PubMed1978

A micromethod for preparation of human macrophage cultures for the study of lymphocyte-macrophage interaction in immune interferon production and blastogenesis.

A new economical and reproducible micromethod for the preparation of human macrophage cultures in wells of a microtiter plate is described. The technique has been employed for the study of events which occur in the interaction of lymphocytes with macrophages in PHA-stimulated immune interferon production and blastogenesis. By comparison with the current Leighton tube macroculture systems, the microculture technique yielded a 7-fold increase in the number of macrophage cultures and a 5-fold increase in the number of T lymphocyte macrophage cultures from a given volume of blood. The replicability from sample to sample with regard to 3H-thymidine incorporation and amount of interferon produced is better in the microculture system than in the Leighton tube system. Such a microculture technique will thus provide a system whereby ready analysis of monocyte-macrophage function and interaction with lymphocytes in numerous disease states can now be realized.

Cell Adhesion↗
PubMed1977

Transfer factor therapy in ataxia--telangiectasia.

The effects of weekly doses of transfer factor in four patients with ataxia--telangiectasia were investigated following a total course of 2 months therapy. Transfer factor administration showed no influence on the absolute lymphocyte counts, T-cell rosettes or antibody titres to EBV, but it caused conversion of skin-test reactivity and production of MIF to various antigens. There was a dissociation in blastic transformation response, the skin-test responses and MIF production. Serum interferon levels were low before, and 2, 6 and 24 hr after, therapy. Clinically no improvement in infections was observed following transfer factor therapy.

Antibodies, Viral↗
PubMed1976

Localization fo the gene AVG for the antiviral expression of immune and classical interferon to the distal portion of the long arm of chromosome 21.

The responses of normal fibroblasts and of fibroblasts trisomic and monosomic for chromosome 21 to exogenously administered virus-induced (classical) and phytohemagglutinin-induced (immune) human interferon were determined. The virus-induced interferon was obtained from leukocytes treated with Sendai virus and from neonatal foreskin fibroblasts treated with Newcastle disease virus. With both classical and immune interferons, the mean response of the trisomic cell lines was three times that of the normal cells, whereas that of the monosomic lines was half or less that of the normal cells, Furthermore, a line trisomic for only the distal half of the long arm of chromosome 21 (q21 leads to qter) also demonstrated increased sensitivity to virus- and phytohemagglutinin-induced interferons, a fact that indicated that the gene responsible for the antiviral effect of interferon, AVG, is located on this part of chromosome 21. Responses to the two categories of interferon (virus-induced and phytohemagglutinin-induced) of individual cell lines of different degrees of sensitivity were strongly correlated (r=0.79). It is concluded, therefore, that despite their physical and antigenic differences, the antiviral expressions of both classical and immune interferons are ultimately mediated by the same genetic locus, AVG.

Cell Line↗
PubMed1975

Studies on mouse Moloney virus induced tumours: I. The detection of p30 as a cytotoxic target on murine Moloney leukaemic spleen cells, and on an in vitro Moloney sarcoma line by antibody mediated cytotoxicity.

Antigenic determinants of p30, the most abundant internal virion protein of C type RNA viruses, were detected on the surface of spleen cells from mice bearing Moloney leukaemia and on an in vitro line of Moloney sarcoma, MSC. On both cell types, these determinants on the p30 molecules served as cytotoxic targets in a xenogenic complement dependent antibody mediated 51Cr release assay. Two antisera were used: a rat anti MLV -M induced lymphoma serum, and an antiserum raised in goats to either disrupted FeLV. The cytotoxic target antigens of these antisera were analysed by inhibition of cytotoxicity with viral and cellular proteins.

Animals↗
PubMed1975

Studies on mouse Moloney virus induced tumours: II. Detection of p30 in the serum of mice with Moloney leukaemia by in vitro blocking of complement dependent antibody mediated cytotoxicity.

Sera from Balb/c mice bearing Moloney leukaemia block complement dependent antibody mediated cytotoxicity of an antiserum prepared in rats against syngeneic Moloney virus induced lymphomata when either spleen cells from mice bearing Moloney leukaemia (M) or an in vitro line of Moloney virus transformed cells (MSC) are used as targets. This antiserum has been shown to recognize p30, the major internal virion protein, as a cytotoxic target on these cells. Viral particles were identified by electron microscopic examination of pelleted material obtained from leukaemic sera after high speed centrifugation. However, removal of virus did not affect the capacity of the leukaemic sera to absorb cytotoxicity of rat ILR-3 for MSC targets, and only depressed somewhat its ability to absorb activity of the same antisera against M targets. Virus-free leukaemic sera also blocks complement dependent antibody mediated cytotoxicity of an antiserum prepared in goats against the gs3 determinant of p30. This indicates that the material in leukaemic sera responsible for the in vitro block of antibody mediated cytotoxicity was p30. A lesser degree of block was observed with sera obtained from normal Balb/c mice, but the nature of material responsible is as yet undefined.

Animals↗