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Biomedical subjects

E Falcoff

Publications and source records attributed to E Falcoff.

At least 55 records · Page 3Linked to original sources
PubMed1984

The value of a radioimmunological monitoring in cancer patients treated with interferon alpha.

Using a radioimmunoassay for human leukocyte interferon (IFN alpha), pharmacokinetic studies were carried out in twelve cancer patients given sequential intramuscular injections of Hu IFN alpha 2. Even though individual monitoring of serum IFN titers emphasized, for a given dose, marked quantitative variations of the observed maximum concentrations, their mean values were found to be dose-dependent (358 +/- 167 U/ml at 30.10(6) U and 1044 +/- 599 U/ml at 100.10(6) U doses). Comparison with bioassay results showed that IFN activities measured in sera were of the same order of magnitude as those calculated from radioimmunoassay standard curves. Data obtained from this series on observed peak time, half-life value and serum concentrations were consistent with those reported by the other groups using recombinant leukocyte interferon in clinical trial. Therefore, radioimmunoassay is an useful method for routinely assaying IFN alpha used either as antitumour or antivirus agent because of its high sensitivity (4 U/ml) and its simplicity.

Adult↗
PubMed1984

Isolation and partial characterization of messenger RNA, from murine T cell hybrids, coding for suppressive immunoglobulin G-binding factor.

Poly A RNA has been isolated from a murine T cell hybridoma ( T2D4 ) that spontaneously secretes suppressive immunoglobulin G-binding factor ( IgGBF ). Translation products, obtained from a rabbit reticulocyte lysate translation system and after injection into Xenopus laevis oocytes, contain material with the biologic activity, the affinity, and the m.w. of murine IgGBF ; it suppresses secondary in vitro IgG antibody production in a dose-dependent fashion. The suppressive factor binds to IgG but not to IgM immunoadsorbents and, after mild NaDodSO4 treatment, dissociates in NaDodSO4 polyacrylamide gels into two peaks at 78 and 40 kD. Translation products from two non- IgGBF -secreting cell lines (BW-5147, a T lymphoma line, and A9, a fibroblast cell line) fail to exert any suppressive activity. On sucrose gradients, the RNA responsible for the biologic activity was found in one major peak located at 11S. IgGBF synthesized in a cellfree translation system by using poly A RNA and sucrose gradient fractions was also characterized by immunoprecipitation with Fc fragments of [35S]methionine-labeled proteins. On NaDodSO4 polyacrylamide gels, it migrates in one peak located at 37 kD. We conclude that IgGBF is coded for by 11S poly A RNA and that no post-translational modifications (other than proteolytic cleavage) are necessary to obtain a biologically active factor with Ig-binding properties.

Animals↗
PubMed1984

[Phase-1 study of the tolerance for increasing doses of recombinant human alpha 2 interferon in patients with advanced cancer].

Thirteen patients with malignant tumors were entered into a phase I trial with recombinant DNA human alpha 2 interferon (IFN alpha 2). The patients were given I.M. escalating doses of IFN alpha 2 ranging from 1-10(6) to 200-10(6) IU with a 72 hours washout between injections. In the majority of the patients, subjective symptoms were noted: fever, headache, chills, nausea, myalgias. Asthenia, anorexia, drowsiness appeared after the highest doses and disappeared without any sequellae. Leucopenia and thrombopenia were seen in 11 out of 13 patients. Hepatocellular toxicity was observed in 9 cases. Cardiac and vascular functions were not impaired by IFN alpha 2. The pharmacokinetic studies showed a maximum serum concentration between 4 and 6 hours after injection and the peak value was directly proportional to the dose. No neutralizing INF alpha 2 serum factor was detected during the treatment. The peak value for serum beta 2 microglobulin occurred 48 hours after and the N.K. activity was variably modified by IFN alpha 2 injections. A major clinical response was observed in 1 case, a minor response in 3 cases and a stabilisation of the disease in 4 cases.

Adult↗
PubMed1983

Action of different gamma interferons on mouse leukemic cells resistant to alpha and beta interferons.

Phytohemagglutinin-induced interferon-gamma (IFN-gamma) was reported to act on mouse leukemic L1210 R cells resistant to IFN-alpha and -beta. Results reported here show that these cells are also sensitive to various preparations of murine IFN-gamma derived from different sources and purified to different degrees and that lymphokines present in the preparations are not involved in the antiviral effect of IFN. In addition, IFN-gamma preparation increases concanavalin A binding to L1210 S and L1210 R cells indicating that the sensitivity of L1210 R cells to IFN-gamma is not limited to its antiviral effect.

Animals↗
PubMed1982

Synergistic activities of type I (alpha, beta) and type II (gamma) murine interferons.

Type I (alpha, beta) and type II (gamma) murine interferons are able to potentiate each other with respect to the inhibition of encephalomyocarditis (EMC) virus and of herpes simplex virus type 1 (HSV-1) multiplication in a murine cell line (DBT). Examination of two double-stranded RNA-dependent enzymes in DBT cells, the 2-5A synthetase and the 67,000 MW protein phosphokinase indicates that mixed interferon preparations act synergistically at least with respect to an increase in the activity of the former enzyme. The results obtained with gamma interferons of different origin and of different specific activity suggest that interferon itself, rather than the lymphokines present in the interferon preparations, is responsible for the synergistic effect.

2',5'-Oligoadenylate Synthetase↗
PubMed1982

Comparison of effects of leukocyte and fibroblast interferon on immunological parameters in cancer patients.

Patients with metastatic cancer were given single intramuscular injections of 10(7) units of partially purified preparations of either leukocyte or fibroblast IFN. Serum levels of inteferon, of beta 2-microglobulin and of carcino-embryonic antigen (CEA), as well as NK activity of circulating lymphocyte, were followed over a period of 96 hr post injection. In confirmation of previous studies, levels of circulating IFN were lower after injection of fibroblast IFN than after injection of leukocyte IFN. Despite this difference in pharmacokinetics, the natural killer activity of circulating lymphocytes was enhanced with both IFNs. Levels of DEA were not influenced by the IFN injections. Leukocyte but not fibroblast IFN caused an increase in serum levels of beta 2-microglobulin in the circulation. A similar difference between leukocyte and fibroblast IFN in their ability to influence the beta 2-microglubulin system was observed in experiments on cell cultures. Only leukocyte IFN was able to cause release of beta 2-microglobulin by either leukocytes or fibroblasts.

Adult↗
PubMed1982

Administration of fibroblast interferon to patients with advanced breast cancer: possible effects on skin metastasis and on hormone receptors.

Eleven patients with metastasized breast cancer received 8 intramuscular injections of 6 x 10(6) units of human fibroblast interferon over a period of 40 days. The injections did not cause local irritation or inflammation. Fever occurred in only 1 of the 11 patients. Although several types of metastases were monitored, only skin nodules consistently (10 out of 11 patients) exhibited changes that were suggestive of a therapeutic effect of the treatment regimen: either a simple decrease in size of some nodules or central necrosis accompanied by an inflammatory reaction. NK-activity of peripheral blood leukocytes was significantly increased after administration of the first dose; the effect of subsequent injections was less clear. Receptors for estrogens and progestogens were increased in the tumor biopsies of 2 out of 2 and 5 out of 6 patients tested respectively.

Breast Neoplasms↗
PubMed1982

Translation of mRNA from phytohemagglutinin-stimulated human lymphocytes: characterization of interferon mRNAs.

Human lymphocytes obtained by cytapheresis were stimulated in spinner culture conditions by nonpurified PHA in order to study the production of gamma interferon, and the characterization of IFN-gamma mRNA. Titers of interferon prepared in 0.6 to 4 1 batches, varied in 20 preparations from 8,000 to 32,000 units/ml. This interferon was unstable at pH 2: the residual antiviral activity after 20 h treatment was less than 3%. Antibodies raised against gamma interferon from Con A and SEA-stimulated lymphocytes neutralized the interferon induced by PHA, indicating that all three preparations are antigenically related. Poly(A)RNA from control, noncultivated lymphocytes and from lymphocytes stimulated by PHA for 18 h were translated in reticulocyte lysates and analysed by polyacrylamide gel electrophoresis. The pattern of synthesized polypeptides was different suggesting modifications in the population of mRNA. When total poly(A)RNA was inoculated into Xenopus Laevis oocytes, interferon activity was found with both, control and stimulated mRNAs although only at low levels in the control. After sucrose gradient fractionation of poly(A)RNA, each fraction was inoculated into oocytes and interferon activity measured in the oocyte bathing medium. A low level was synthesized by the RNA fractions around 28 S from control as well as from stimulated lymphocytes. These interferons were not neutralized by anti-IFN-alpha or anti-IFN-gamma sera but they were neutralized by anti-IFN-beta serum. Only the 16 S RNA fraction from PHA-stimulated lymphocytes induced high levels of interferon in oocytes. This interferon has been characterized as gamma interferon. Each fraction obtained from sucrose gradients on poly(A)RNA from control and PHA-stimulated lymphocytes was translated in reticulocyte lysate. Gel analysis of the products showed striking differences when the same fraction of both RNAs were compared. Concerning particularly the 16 S RNA from PHA-stimulated lymphocytes, where gamma interferon mRNA was present, polypeptides ranged from 15 to 55 K with a bulk around 45 K, indicating heterogeneous RNA molecules.

Animals↗
PubMed1982

Chromatographic behavior, purification, and properties of mouse BCG-induced gamma interferon.

Mouse gamma antigen-induced interferon (IFN) was produced in vivo by injecting PPD into BCG-sensitized mice. The IFN activity present in the serum was partially purified by adsorption on silicic acid and elution with buffer containing ethylene glycol, followed by chromatography of the eluate on Blue-Trisacryl. This method yielded IFN preparations with a specific activity of 1.5 x 10(5) mu/mg protein (10,000-fold purification). BCG IFN showed high affinity for polynucleotides and apparent hydrophobicity, two characteristics which allowed it to bind to Poly I agarose and Phenyl Sepharose, respectively. The chromatographic behavior of BCG IFN on Con A Sepharose indicates that BCG IFN is glycosylated. However, binding of the antiviral activity to the lectin column was only possible when purified IFN was used for chromatography. Although the purification method described here allowed purification of the antiviral activity as a major fraction, molecular heterogeneity was detected under certain chromatographic conditions. Two fractions with different molecular weights of 27,000 and 56,000, respectively, were always obtained by sieving purified BCG IFN on Sephacryl S 200.

Animals↗
PubMed1981

Effect of various interferons on the spontaneous cytotoxicity exerted by lymphocytes from normal and tumor-bearing patients.

Natural killer cell activity, which represents the spontaneous cytotoxicity of lymphocytes toward tumor cells, has been measured in 173 tumor-bearing patients and 25 healthy volunteers; no significant difference was found in mean natural killer cell activity between the two groups. The parameters of interferon-induced activation of natural killer cells were studied in order to provide a suitable test for monitoring the effect of interferon in clinical trials. The three interferons tested (leukocyte, lymphoblastoid, and fibroblast) were equally active in inducing spontaneous cytotoxicity of lymphocytes from all healthy individuals and tumor-bearing patients studied. Incubation for one hr with 100 units of interferon was sufficient to increase spontaneous cytotoxicity activity, the maximum effect being obtained when lymphocytes were incubated with 1000 units of any of the interferons used. This effect was blocked with the appropriate antiinterferon sera. The target cells for interferon seem to be positive Fc gamma receptor lymphocytes.

Adult↗
PubMed1980

Studies on Brucella interferon: chromatographic behaviour and purification.

Interferon was induced by infecting mice with Brucella suis. Serum containing interferon activity was analyzed by chromatography on Concanavalian A-Sepharose and Phenyl-Sepharose CL-4B columns. Antiviral activity was completely retained by the lectin column indicating that all the interferon molecules are glycosylated. The chromatographic behaviour of Brucella interferon on Phenyl-Sepharose CL-4B shows that, like other interferons, Brucella displays hydrophobic properties. However, the hydrophobicity of the interferon molecule was masked in the crude preparation and was only detectable when purified Brucella interferon was used for chromatography. The antigenic properties of Brucella interferon provided the means for developing an affinity chromatographic method resulting in about 60,000 fold purification. As in the case of viral interferon, treatment of L cells with Brucella interferon induced specific enhanced in vitro phosphorylation of a 67,000 molecular weight protein after incubation of cell extracts with double-stranded RNA and [gamma-32P] ATP.

Adenosine Triphosphate↗
PubMed1980

Mouse fibroblast (type I) and immune (type II) interferons: pronounced differences in affinity for gangliosides and in antiviral and antigrowth effects on mouse leukemia L-1210R cells.

Different interferons can be obtained from the same animal species depending on the cells and (or) the inducers used. Interferons of type I and type II differ not only antigenically but also in molecular weight and stability at low pH. We have investigated whether mouse type I and type II interferons also differ in properties relating to their biological action. We present evidence which suggests that the molecular mechanism leading to antiviral and antigrowth effects induced by both types of interferon in susceptible cells must differ in at least one important step. Antiviral and antigrowth activities of type I but not of type II interferon are both inhibited when gangliosides are added to cell cultures together with the interferon. Whereas type I interferon strongly binds to ganglioside affinity columns and can be eluted with solutions of N-acetylneuraminyllactose, type II interferon passes through such columns unretarded. L-1210 mouse leukemia cells (L-1210S) respond equally well to antiviral and antigrowth activities of type I and type II interferons. Type I interferon-resistant L-1210 cells (L-1210R), derived from L-1210S cells after continuous culture in the presence of mouse fibroblast interferon, lack antiviral and antigrowth response to mouse type I interferon [Gresser, I., Bandu, H.T. & Brouty-Boyé, D. (1974) J. Natl. Cancer Inst. 52, 553-559]. However, these cells display the same sensitivity toward type II interferon as do the parent L-1210S cells from which they were derived and respond equally well to its antiviral and antigrowth activities.

Animals↗
PubMed1980

Action of murine gamma (immune)interferon on beta (fibroblast)-interferon resistant L 1210 and embryonal carcinoma cells.

Treatment of leukaemic mouse L 1210 S cells with beta or gamma interferon results in the development of antiviral and anticellular effects, both of which are also induced by interferon in L 1210 R cells selected for their resistance to gamma-interferon. Here we show that treatment of L 1210 S cells with beta or gamma interferon results in the induction of two double-stranded (ds) RNA dependent enzymes which have been described previously in beta and gamma-interferon treated mouse L-929 cells: pppA (2'p5'A)n synthetase and protein kinase(s). Treatment of L 1210 R cells with beta-interferon does not result in the induction of any detectable enhanced pppA (2'p5'A)n synthetase and protein kinase activities whereas gamma-interferon is capable of inducing both of these enzymes. These results indicate that although beta and gamma-interferon induce similar intracellular events, they may have different mechanism of interaction with their target cells. In addition, here we show that similar to the action of beta-interferon, treatment of mouse embryonal carcinoma cells with gamma-interferon results in the induction of pppA (2'p5'A)n synthetase in the absence of any detectable protein kinase activity or any apparent development of antiviral and anti-cellular effects. The significance of this in relation to the mechanism of action of interferon is discussed.

2',5'-Oligoadenylate Synthetase↗