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Biomedical subjects

R M Friedman

Publications and source records attributed to R M Friedman.

At least 181 records · Page 10Linked to original sources
PubMed1979

Induction of simian virus 40-specific tumour rejection by the Ad2+ND2 hybrid virus.

Immunization of BALB/c mice with Ad2+ND2, a non-defective hybrid virus containing about half of the early region of simian virus 40 (SV40) DNA covalently integrated into the human adenovirus 2 (Ad2) genome, can confer protection against subsequent challenge by syngeneic SV40 tumour cells. Analysis of subcellular fractions from Ad2+ND2-infected cells shows a close correlation between the tumour rejection activity and the presence of the two SV40-specific proteins induced by this hybrid virus. These two proteins, with mol. wt. of 56 000 (56K) and 42 000 (42K), can be specifically immunoprecipitated using sera obtained from hamsters bearing SV40-induced tumours. Such immunoprecipitates, which contain no detectable contaminating components as determined by polyacrylamide gel electrophoresis, can efficiently immunize mice against SV40 tumour challenge, suggesting that the 56K and 42K proteins are directly responsible for the induction of tumour rejection. Moreover, we have found, by immunoprecipitation, a novel antigen in SV40-transformed BALB/c cells, also of 56 000 mol. wt.; possibly, this 56K protein is responsible for induction of transplantation immunity in SV40-transformed cells.

Adenoviruses, Human↗
PubMed1978

Membrane alterations following interferon treatment.

Interferon treatment appears to induce a number of changes in the plasma membrane of uninfected cells. Interferon treatment altered the surface exposure of gangliosides of both Ly and KB cell membranes. The differences were found in the amount and pattern of incorporation of tritium after galactose oxidase treatment. In AKR,C- (AKR-2B) mouse cells, not only was there an apparent increase in the number of intramembranous particles in response to treatment with interferon but also the kinetics of the increase followed that of the establishment of the antiviral activity. The buoyant density of plasma membrane was also found to be significantly increased in interferon-treated cells. Moloney murine leukemia virus produced in interferon-treated mouse thymus and bone marrow cells had a high particle to infectivity ration. This virus contained a prominent glycoprotein with a molecular weight of about 85,000. This large glycoprotein was only a very minor component of Moloney leukemia virus produced in control TB cells and might be an uncleaved precursor to gp 69-71.

Cell Membrane↗
PubMed1978

Physical, morphological, and biochemical alterations in the membrane of AKR mouse cells after interferon treatment.

Interferon treatment of AKR,C- cells was followed by the establishment of an antiviral state and apparently concomitant morphological, physical, and biochemical alterations of the cell plasma membrane. The density of the plasma membrane was significant altered, and the concentration of some plasma membrane glycoproteins and the number of intramembranous particles observed in freeze-fracture electron micrographs were increased. A parallel increase in the concentration of intramembranous particles and the resistance to viral infection during interferon treatment as well as their parallel decrease upon removal of interferon suggests a relationship between the particle density and the establishment of the antiviral state.

Animals↗
PubMed1978

Tumor-specific transplantation antigen: use of the Ad2+ND1 hybrid virus to identify the protein responsible for simian virus 40 tumor rejection and its genetic origin.

Cells transformed by simian virus 40 (SV40) possess a tumor-specific transplantation antigen (TSTA) that has the property of immunizing animals against syngeneic tumor challenge. We find that the early SV40 DNA segment present in the human adenovirus 2 (Ad2)-SV40 hybrid, Ad2+ND1, is sufficient to induce this SV40-specific TSTA in BALB/c mice. Moreover, studies on the intracellular distribution of TSTA activity in Ad2+ND1-infected cells, as determined by the ability of various subcellular fractions to immunize mice against syngeneic tumor challenge, have suggested a correlation between this biological activity and the presence of the SV40-specific 28,000Mr protein in coded by this hybrid virus. Both the TSTA activity and the 28,000 Mr protein are found in the plasma membrane fraction and in the perinuclear region of infected cells but are virtually undetectable in the cytoplasmic fraction. Using a hamster antitumor antiserum that can specifically immunoprecipitate the 28,000 Mr protein, we are able to demonstrate a loss of TSTA activity concomitant with the removal of this SV40-coded protein. Thus, it appears that antigenic determinants responsible for SV40-specific tumor rejection in mice are contained within the 28,000 Mr protein coded for by the early SV40 DNA segment that extends from 0.17 to 0.28 map unit.

Adenoviruses, Human↗
PubMed1978

Biosynthesis, immunological specificity, and intracellular distribution of the simian virus 40-specific protein induced by the nondefective hybrid Ad2+ND1.

Ad2(+)ND(1), a nondefective hybrid virus containing a segment of the early region of simian virus 40 (SV40) DNA covalently inserted into the human adenovirus 2 genome, enhances the growth of human adenoviruses in simian cells and induces the SV40 U antigen. This hybrid previously has been shown to code for a 28,000 (28K) molecular weight protein not present in wild-type adenovirus 2-infected cells. By radioimmunoprecipitation using sera from hamsters bearing SV40-specific tumors, we have established that the Ad2(+)ND(1)-induced 28K protein is SV40-specific. This Ad2(+)ND(1)-induced protein is synthesized as a 30K molecular weight precursor, which is detectable only when infected cells are pulse-labeled in the presence of the protease inhibitor tosylamino phenylethyl chloromethyl ketone. Upon fractionation of labeled cell extracts, about 80% of the 28K protein is found in the plasma membrane fraction, whereas the remaining 20% is associated with the outer nuclear membrane. This protein is not detectable either in the nucleus or in the cytoplasm. Blockage of proteolytic cleavage by tosylamino phenylethyl chloromethyl ketone did not alter the topographic distribution of this SV40-specific protein, although the amount of the precursor protein in the outer nuclear membrane increased fourfold while that in the plasma membrane was proportionately decreased. This result suggests that the 28K protein is transferred from the outer nuclear membrane to the plasma membrane after posttranslational cleavage of the 30K precursor polypeptide. These data offer further support to the proposal that the 28K protein contains the determinants for SV40 U antigen and is responsible for SV40 enhancement of adenovirus growth in simian cells.

Adenoviruses, Human↗
PubMed1978

Relationships of the structure and function of the interferon receptor to hormone receptors and establishment of the antiviral state.

This report describes similarities between the structure and function of the interferon receptor and receptors for glycoprotein hormones and several bacterial toxins. Specifically, it describes several common molecular and mechanistic elements, including: (a) the presence of a glycoprotein as well as a ganglioside component in the receptor; (b) changes in membrane structure as a consequence of interferon action; (c) interferon-induced intracellular cyclic adenosine 3':5'-monophosphate changes; and (d) alterations in the flux of certain ions across the membrane. Since interferon has an antiviral effect, these results define a relationship between hormonal perturbation of cellular events and the ability of an agent to prevent or suppress viral infections of cells. Further definition of these relationships should be important to our understanding of the oncogenic state, of hormonal effects on the oncogenic state, and of other human diseases in which hormonal perturbations of non-target tissues or cross-reactivity of receptors could be pathogenic.

Binding Sites↗
PubMed1977

The effect of interferon on de novo infection of Moloney murine leukemia virus.

The mode of action of interferon in de novo Moloney murine leukemia virus (Mo-MuLV) infection of mouse bone marrow/thymus (TB) cells was studied. Our results indicate that in interferon-treated cells, there is approximately a 2000 fold decrease in the production of infectious MuLV, but only a 10-20 fold decrease in the level of viral specific extracellular reverse transcriptase activity, and only about a 2 fold difference in the number of virus particles observed on the cell membrane as determined by scanning electron microscopic (SEM) studies. Transmission electron microscopic (TEM) studies showed that the proportion of early budding virions, which have shallow crescent-shaped ribonucleoprotein cores (Figure 3A), to virions in later stages of assembly (Figures 3B-3D) is relatively higher in interferon-treated cells than in the untreated controls. From a temperature shift-down experiment on a temperature-sensitive mutant of MuLV, ts 3, which produces viral particles that fail to dissociate from the cell surface at the nonpermissive temperature, we demonstrated that ts 3 virions partially assembled on the cell membrane prior to the addition of interferon are able to complete assembly and to dissociate from the cell membrane on temperature shift-down in the presence of interferon action. Our data suggest that interferon neither inhibits the late stages of virion assembly at which ts 3 virions are arrested at the nonpermissive temperature nor prevents release of the virions. Our findings also indicate that in interferon-treated cells, most of the extracellular virions are noninfectious.

Cell Line↗
PubMed1977

Interferon inhibits mouse leukaemia virus release: an electron microscope study.

Scanning electron microscopy of AKR cells chronically infected with AKR mouse leukaemia virus revealed that the number of budding virions was greatly increased in interferon-treated cells. These results, together with previous biochemical findings, suggest that in this system, interferon inhibits a late stage of virus assembly or release.

AKR murine leukemia virus↗
PubMed1977

Simian virus 40-specific ribosome-binding proteins induced by a nondefective adenovirus 2-simian virus 40 hybrid.

We have studied the intracellular distribution of the two simian virus 40-specific proteins, with apparent molecular weights of 56,000 and 42,000, detectable in human KB cells infected by a nondefective adenovirus 2-simian virus 40 hybrid, Ad2+ND2. After a 20-min pulse of [35S]methionine, about two-thirds of the newly synthesized 56K protein and one-third of the 42K protein were found localized on the plasma membrane. The remainder of each protein was found in the cytoplasm, whereas the nuclear fraction was virtually free of either component. A significant portion of both proteins present in the cytoplasmic fraction was complexed to the 40S ribosomal subunits and was not removed by treatment with 0.5 M KCl. Moreover, the portion that was found free in the cytoplasm could bind preferentially and quantitatively to purified 40S ribosomes in vitro, leading us to propose that these simian virus 40 proteins may act as translational control elements in cells.

Adenoviruses, Human↗
PubMed1976

The effect of lanthanide ions on enteropeptidase-catalyzed activation of trypsinogen.

Rare earths were found to be powerful inhibitors of enteropeptidase-catalyzed (enterokinase, EC 3.4.21.9) activation of trypsinogen. Inhibition was complete at a La3+ concentration of 12.5-10(-6) M in the assay system used and still detectable at a concentration of 1.25-10(-6) M. Inhibition was observed with all lanthanides tested. No significant differences between individual metals could be established under the conditions of the inhibition assay. Increasing ionic strength decreased enzyme activity and progressively diminished the inhibitory effect of rare earth ions suggesting an electrostatic basis for the mechanism of this inhibition. La3+ did not significantly affect enteropeptidase-mediated hydrolysis of N-benzoyl-L-arginine ethyl ester. Its inhibitory effect on activation of trypsinogen by enteropeptidase, therefore, must be attributed to interaction with the zymogen rather than the enzyme. Kinetic measurements show that inhibition by rare earths is noncompetitive in nature. Binding of lanthanides to the tetraaspartyl sequence near the aminoterminus of trypsinogen may prevent this group from interacting with a critical specificity subsite on the enzyme.

Duodenum↗