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Biomedical subjects

R Falcoff

Publications and source records attributed to R Falcoff.

At least 37 records · Page 2Linked to original sources
PubMed1985

Correlation between endogenous interferon and the clinical evolution of patients with Argentine hemorrhagic fever.

To explore the endogenous interferon levels in patients of Argentine hemorrhagic fever (AHF) with different clinical evolution of the disease, 29 fatal and 33 surviving cases of AHF were analyzed. As previously reported, the titers of endogenous alpha-IFN in patients with AHF are very high, generally between 2,000 and 64,000 IU/ml. Thus far, these are the highest levels of circulating interferon detected in any human viral disease. In this study it was found that during the second week of evolution the titers of interferon were significantly higher in fatal cases than in survivors. Therefore, very high levels of interferon have a prognostic value in AHF.

Follow-Up Studies↗
PubMed1985

Characterization of antibodies against recombinant HuIFN-gamma produced by hybridoma cells.

Balbc/c mice were immunized with purified recombinant E. coli-derived human gamma-interferon (HuIFN-gamma). Their spleen cells were fused with a mouse myeloma cell line (Sp2/0). Hybridomas producing antibodies reacting with HuIFN-gamma were screened by a soluble-phase radioimmunoassay using pure 125I-labeled cloned IFN-gamma as antigen, and tested for their ability to neutralize the antiviral activity of IFN. Three hybridomas S1-1, S1-2, and S1-3, were cloned and subcloned and remained stable. Although the antibodies produced by clones S1-1 and S1-2 were both able to neutralize specifically the antiviral activity of natural and recombinant HuIFN-gamma, they appeared to recognize different epitopes on the HuIFN-gamma molecule. The antibodies produced by the S1-3 clone failed to neutralize the antiviral activity of either interferon. The antibodies from all three clones were characterized as IgG1 subclass. Their affinity constants were determined from competitive inhibition curves and ranged from 1 to 4.3 X 10(8) M-1.

Animals↗
PubMed1985

SLO4, a new interferon inducer isolated from Klebsiella pneumoniae and Escherichia coli.

A product isolated from Klebsiella pneumoniae and Escherichia coli, coded SLO4, has been shown to be effective in endogenous interferon induction in vivo in mouse when administered IP or IV, and in vitro with human leukocyte cultures. In these two systems induced interferon was defined. The inducer has not yet been characterized but seems not to belong to any components known to be interferon inducers such as viral particles, nucleic acids or endotoxins. An analytical study will be carried out to specify the constitution of this interferon inducer.

Animals↗
PubMed1984

Helper activity for antibody synthesis encoded by mRNA extracted from human peripheral blood mononuclear cells.

Translation products in Xenopus laevis of mRNA from human peripheral blood mononuclear cells were tested for their capacity to replace T cells in the anti-SRBC response of nude spleen cells. When the starting material came from PHA or FCS-stimulated lymphocytes, the translated lymphokines, displaying such a B cell helper activity were found to be encoded by mRNA sedimenting at 6-7S and 13S on a sucrose density gradient. 6-7S mRNA from control, non-stimulated lymphocytes was also able to code for B cell helper activity. Thorough T-cell depletion of mouse responder cell populations left unchanged the activity of 6-7S mRNA products while preventing that of 13S products. The latter were found to contain IL-2, which suggests that their action on B cells was indirect, mediated by T-cell stimulation.

Animals↗
PubMed1984

Kinetics of messenger accumulation coding for IFN gamma, related to modifications in the poly(A) RNA population of activated human lymphocytes.

Exposure of human lymphocytes to a mitogen induces the appearance of newly synthesized RNAs and proteins. This study describes the changes in overall synthesis as measured by pulse labelling of PHA treated lymphocytes as well as a qualitative analysis of the protein synthetic patterns "in vivo" and "in vitro". Both the levels of RNA and protein synthesis increase drastically in PHA stimulated cells, while cultures incubated without mitogen remained at background levels. The low translational activity in control cells is not due to the absence of messengers since the extracted RNAs clearly direct the synthesis of high molecular weight proteins when translated "in vitro". A number of qualitative differences are seen in the "in vitro" translation of RNA extracted from induced and non-induced lymphocytes, although the apparent protein synthetic pattern "in vivo" remains identical. The secretion of IFN- gamma is one of the newly expressed functions in stimulated lymphocytes and therefore has been studied more detailed in a time-course of the messenger level compared to the secreted activity of the medium. A specific probe was used to quantitate in Northern blot's the accumulation of mRNA coding for IFN- gamma.

Animals↗
PubMed1984

Studies on purification of human gamma interferon: chromatographic behavior of accompanying IL2 and B-cell helper activity.

Gamma interferon (gamma IFN) was produced in human lymphocyte cultures stimulated by PHA. Titers were in the range of 10,000-30,000 U/ml. Crude gamma IFN was adsorbed on silicic acid, from which the antiviral activity was eluted by a buffer containing a high salt concentration and ethylene glycol. This treatment allowed quantitative recovery of gamma IFN with a specific activity of 5 X 10(5)-1 X 10(6) U/mg of proteins. IL2 and B-cell helper activities were adsorbed and eluted from silicic acid together with the antiviral activity. This finding might be of practical interest for the purification of these lymphokines, particularly IL2. Gamma interferon was further purified on Blue Sepharose to a specific activity of 2 X 10(7) U/mg. The resulting preparations still contained IL2 and B cell helper activities. However, taking advantage of the differences in apparent hydrophobicity and in isoelectric point, we were able to dissociate antiviral activity from lymphokines. Such dissociation should facilitate the study of the biological properties of human natural gamma IFN.

Adsorption↗
PubMed1984

Endogenous interferon in Argentine hemorrhagic fever.

The induction of endogenous interferon (IFN) was studied in 28 cases of Argentine hemorrhagic fever (AHF), a severe systemic disease caused by Junin virus. Serum samples were taken daily during the acute period, both before and after administration of immune plasma. This form of treatment has been found to reduce mortality when given early in the course of AHF. High titers of circulating IFN were present in the serum samples taken before treatment. IFN titers drastically dropped after transfusion of immune plasma. The antiviral activity was stable at pH 2 and was completely neutralized only by antibodies against IFN-alpha. Thus, we concluded that circulating endogenous IFN in patients with AHF can be considered as typical IFN-alpha. Fever, chills, and backache were associated with the higher levels of IFN. An inverse correlation between days of evolution of the disease and IFN activity was also observed.

Back Pain↗
PubMed1982

[Incubation of Beef tRNALeu in interferon-treated cells lysate leads to a partial removal of the 3' terminal sequence (author's transl)].

Beef tRNALeu and tRNAArg labeled with [32P]-phosphate at their 3' hydroxyl or 5'-phosphate ends have been incubated in the presence of lysates of interferon-treated Mouse cells. The degradation of the two tRNAs has been followed by polyacrylamide slab gel electrophoresis. In all cases, the incubation leads to a degradation of the tRNAs to a variable extent, but tRNALeu is degraded much faster than tRNAArg. This study, provides evidence that the 3' terminal C - C - A is the primary target of degradation leading to a very fast inactivation of tRNALeu and to the inhibition of translation of exogenous and synthetic mRNAs.

Animals↗
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↗
PubMed1981

Effect of interferon on transient shut-off of cellular RNA and protein synthesis induced by Mengo virus infection.

Infection of mouse L929 cells with Mengo virus resulted in a rapid shut-off of cellular RNA synthesis followed within the first hours post infection by a gradual decrease in host protein synthesis. Pretreatment of the cells with high doses of interferon, blocking viral multiplication, did not affect the virus-induced shut-off of host macromolecular synthesis. In these interferon-treated cells the 2',5'A-activated nuclease may account for the degradation of viral RNA, soon after its replication. However, the inhibition of host protein synthesis could not be explained by this mechanism. Poly(A)-containing RNA, present in interferon-treated and infected cells, amounted to as much as 70% of that present in interferon-treated, noninfected cells. On the other hand, extracted cytoplasmic RNA was efficiently translated in a reticulocyte lysate, showing that extensive mRNA degradation was not involved in the inhibition of host protein synthesis. In the continued presence of interferon, the virus-induced shut-off was found to be transient. Late in infection, RNA synthesis was found to recover, followed by recovery of protein synthesis and survival of the cells.

Enterovirus Infections↗