[Constant presence of alpha interferon in human amniotic fluid].
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Biomedical subjects
Publications and source records attributed to C Chany.
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beta and gamma interferons were found to enhance the organization of microfilaments, intermediate filaments, and fibronectin in the murine sarcoma virus (MSV)-transformed cell line. Furthermore, both interferons increased the number of intermediate-type junctions. Sodium butyrate was also found to act in a similar way and, when associated with interferon, an additive effect was observed. In the cell line, cultured for many passages in the presence of beta interferon (MSV-IF+), the cytoskeletal network and the extra-cellular matrix were highly developed and were reminiscent of a normal cell. These results could explain some of the biological actions of interferon, such as increased cell adhesion to the substratum and decreased cell motility.
The transformation of murine BALB/c embryonic fibroblasts by murine sarcoma virus, Moloney strain, followed by prolonged treatment with murine interferon, resulted in the appearance of a new cell population (MSV-IF+). These MSV-IF+ cells are characterized by the recovery of a normal phenotype, contact inhibition, and lack of colony formation in agar. This phenotypic change of the MSV-IF+ cells is associated to the neosynthesis of a dense fibrous matrix beyond the cell periphery. Ultrastructural studies using peroxidase-labeled antibodies enabled us to localize the extracellular distribution of fibronectin and collagen in the MSV-IF+ cell line, compared to normal BALB/c and murine sarcoma virus-transformed cells. In parallel, a significant increase of collagen and fibronectin deposit in the intercellular space of interferon-treated murine sarcoma virus-transformed cells was observed.
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The existence of a widely spread corona virus epidemic enabled us to associate this infection with necrotizing hemorrhagic enterocolitis in newborn infants. Virus is detected in the stools by direct electron microscopic examination. Virions are found agglutinated in the gut during convalescence, as they are by circulating antibodies. Arguments supporting a possible etiological role of this infection are given.
Interferon treatment of sensitized T lymphocytes enhances cytotoxicity against target cells. On the contrary, the same treatment of the target cells alone protects them, whatever the cytotoxicity of effector cells might be. We suggest that the cells having once survived contact with cytotoxic T lymphocytes could become resistant to any new attack by the same cells.
Type I interferon was released from human lymphocytes cultured on cells infected with Herpesvirus and fixed with glutaraldehyde. This process of interferon induction did not involve histocompatibility antigens nor the Herpes immunity of the lymphocyte donors. Type I interferon can also be induced after interaction between lymphocytes and other intranuclear replicating virus infected cells.
A plasmid containing two cloned hepatitis B virus genomes in a tandem head-to-tail arrangement has been introduced into mouse fibroblasts by using cotransformation with the cloned herpes simplex virus thymidine kinase gene. Several copies of the plasmid were integrated into high molecular weight cellular DNA. The original tandem structure of the hepatitis B virus DNA was conserved. Hepatitis B surface antigen was synthesized by all the 15 clones examined. The other viral antigens were not detected. The surface antigen was excreted into the cell culture medium as particles having the same characteristics as those found in human serum. It is estimated that 2-4 X 10(4) particles were produced per mouse cell per 24 hr in two clones. This value corresponds to approximately 2-4 X 10(6) surface antigen polypeptides per cell per 24 hr.
In transformed mouse embryo cells, type II interferon had much less antiviral activity than type I interferon. In non-transformed cells, the two interferons had similar high activity, Reversal of the phenotype of Moloney sarcoma virus (MSV) transformed cells by sodium butyrate restored their sensitivity to the antiviral action of type II interferon. Additional evidence for a role of the cytoskeletal network in the action of type II interferon is that its antiviral effect is reduced by cytochalasin B, colchicine or vinblastine. MSV-transformed cells, selected for their resistance to the antiviral action of type I interferon, were sensitive to type II interferon. These differences in the effects of type I and II interferon on transformed cells are at present unexplained, but suggest that they have at least partially separate mechanisms of action.
Interferon, like cholera toxin, induces in mouse adrenal YI cells the production of delta 3(4) ketosteroids. In parallel, cyclic AMP (cAMP) is activated. At high concentrations, mouse but not human interferon induces a cell rounding effect, similar to that obtained with cholera toxin. In YI cells transformed by simian adenovirus 7, production of cAMP is still increased by that of steroids is blocked. The role if interferon in these cellular events is discussed.
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In order to explore by immunological methods the interferon-induced cell membrane modulation, the effect of interferon in parental and monkey-mouse hybrid cells was studied in the presence of sensitized lymphocytes from isologous mice. After primary immunization to the hybrids, both parental interferons increased the lymphocyte-induced specific cytotoxicity in the same hybrid cells used as targets. In addition, a significnt increase of spontaneous lysis due to the two interferons was observed. In contrast, after secondary sensitization, in spite of the higher specific cytotoxicity induced by the lymphocytes, the same interferon preparation significantly protected the cells. These results are probably related to a greater number of sensitized effector cells after secondary sensitizationn. It is likely that, although interferon increases the affinity of sensitized T lymphocytes for the target cell membrane, in case of unsuccessful encounters, the target cells become resistant to new hits. Interferon could augment the number of such immune cells.
Analysis of a great number of independent hamster-human and mouse-chimpanzee somatic cell hybrid clones confirms the role of chromosome 9 as carrying one or more primate beta interferon genes. The presence of chromosome 13 in producing hybrids and its absence in all non producing clones must be kept in mind for future studies. The strong negative regulation of interferon production in the parental hamster cells also affects the human gene product. The UV irradiation target for these regulatory genes is significantly greater than the structural genes responsible for interferon production.
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Sodium butyrate enhances the antiviral and anticellular action of interferon in MSV-transformed cells but has no such effect in normal cells. The increased sensitivity could be mediated at least partially by the butyrate-induced elaboration of the microtubule and microfilament network.
Crude extracts from the human glomerular basement membranes solubilized by pepsin or bacterial collagenase agglutinate normal or transformed human cells. Cytoagglutination is inhibited by N-acetyl-osamines. These properties are reminiscent of lectins. When agglutinated cells are incubated for an additional 20 hrs. period in minimal serum free medium but in presence of these basement membrane extracts, they attach to the glass and spread out.
The association of relatively low doses of interferon with an immunostimulant, isoprinosine, enhanced the antitumor effect of interferon. Each mouse was inoculated with 10(6) Crocker Tumor 180/TG cells. The best results were obtained when both interferon and isoprinosine were injected three times a week for 1 month. Under these conditions, the mean survival time increased from 26 days in the controls to 45 days in the interferon-treated group to 64 days when both agents were used. Isoprinosine alone had no effect. The final survival rate increased from 1 mouse out of 50 mice in the control group to 10 mice out of 50 in the interferon-treated groups and to 25 mice out of 50 with the combined treatment.