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Biomedical subjects

A Billiau

Publications and source records attributed to A Billiau.

At least 19 recordsLinked to original sources
PubMed1979

Human fibroblast interferon for clinical trials: production, partial purification, and characterization.

The production and partial purification of human fibroblast interferon for performing clinical trials is described. The interferon was produced by superinduction (exposure to riboinosinic-ribocytidylic acid, cycloheximide, and actinomycin D) of large numbers of human diploid fibroblast cultures. The yield averaged 750 units per cm(2) of culture area. The interferon was concentrated and purified by a two-step procedure involving acid desorption from controlled-pore glass beads and dialysis against polyethylene glycol. Human plasma protein was added as a stabilizer. The lyophilized end product had a specific activity of 0.5 x 10(6) to 1 x 10(6) units/mg of protein; it could be reconstituted for injection at a concentration of 2 x 10(6) units/ml. The composition of this interferon was characterized by crossed immunoelectrophoresis with polyspecific antibodies prepared against the principal sources of potential contaminants: human serum, calf serum, and normal human fibroblasts. Several components of each source were detected. Although the major component of calf serum, bovine serum albumin, was absent, other minor components were retained by the production and purification sequence. One of the main contaminants of fibroblast origin was found to be fibronectin.

Cells, Cultured↗
PubMed1979

Human fibroblast interferon for clinical trials: pharmacokinetics and tolerability in experimental animals and humans.

Human fibroblast interferon (F-interferon) purified by adsorption on controlled-pore glass was given intramuscularly to patients at daily dosages of up to 20 x 10(6) units. Serum levels of antiviral activity were low or undetectable. In contrast, reasonably high serum titers were found in patients receiving interferon prepared from leukocytes (L-interferon). Similarly, in rabbits lower serum titers were seen with F-interferon than with L-interferon. These results are at variance with those obtained earlier (V. G. Edy, A. Billiau, and P. De Somer, J. Infect. Dis. 133:A18-A21, 1976). Possible explanations for this discrepancy are discussed. The F-interferon evoked febrile reactions, delayed skin reactivity, and transitory lymphopenia in humans. Some patients developed an allergic state of the reaginic type as evidenced by a weal and flare reaction after intradermal challenge. However, these patients did not show allergic symptoms after intramuscular injections. None of the side effects was severe enough to prohibit continuation of the treatment; most of them seemed to be due to contaminants not removed by the purification method. The possibility is considered that some of the side effects, e.g., delayed skin reactivity, are sufficiently specific to justify identification of the active principals.

Adolescent↗
PubMed1978

Interferon inhibits C-type virus at a posttranscriptional, prerelease step.

The mode of action of interferon in JLSV 5-cells, chronically infected with Rauscher murine leukemia virus (MLV), was studied by examining the fate of preexisting labelled viral RNA in interferon-treated cells and by determining the infectivity/physical particle ratio of cell-associated and extracellular virus. Interferon added together with 3H-uridine inhibited the production of labelled virus particles even when it was only allowed to act after all viral RNA synthesis had been stopped by actinomycin D. This indicated that the interferon-induced antiviral state primarily functions at a posttranscriptional step. When interferon was given after a 3H-uridine pulse label and arrest of label incorporation by glucosamine and unlabelled uridine, it prevented a portion of the preexisting radioactive RNA from occurring in extracellular particles. However, part of the labelled viral RNA had reached a stage beyond which interferon could not prevent it from occurring in extracellular virus particles. The notion that interferon primarily affects release of fully assembled and enveloped MLV particles may be eliminated: interferon-treatment did not affect the release of particle-bound reverse transcriptase in cells treated with cycloheximide after the antiviral state had been established. It was confirmed that interferon-treated JLSV 5-cells contained an increased number of virus particles associated with the cell membrane. However, these particles were found to have a reduced infectivity compared to those associated with control cells, thus confirming the view that virions produced by interferon-treated cells are defective; perhaps lacking in certain components.

Cell Line↗
PubMed1978

Infection of human cell cultures with bovine visna virus.

Fibroblastoid cell cultures derived from leukaemic bone marrow were successfully infected with BVV. After 2 months of subcultivation the cultures showed the appearance of foci of altered cells, suggestive of malignant transformation. Such foci were absent in non-inoculated cultures. Both control and inoculated cultures had a limited life span, i.e. neither of them could be developed into continuous transformed cell lines. The presence of at least some BVV genome functions in the inoculated cells was demonstrated (i) by immunofluorescence using a reference BVV serum, (ii) by detection in the supernatant culture fluid of sedimentable particles bearing RNA-dependent DNA polymerase activity with preference for Mg2+ ions, and (iii) by electron microscopic detection of scarce cell-associated virus particles in one of the infected cultures. Infectious BVV could not be rescued. In contrast to leukaemic bone marrow cultures, diploid human embryonic fibroblasts of various origin could not be infected with BVV.

Animals↗
PubMed1978

Double-blind study of interferon administration in renal transplant recipients.

In a double-blind trial renal allograft recipients were treated with fibroblast interferon preparations for 3 months in an attempt to prevent viral infections. Interferon therapy did not reduce the overall incidence of viral infections. No adverse effects were noted on liver function, platelet counts, or leucocyte counts, or acute rejection episodes.

Adolescent↗
PubMed1978

Interferon treatment of NZB mice: accelerated progression of autoimmune disease.

The effect of long-term administration of interferon in New Zealand Black and New Zealand Black/New Zealand White F1 hybrid mice was studied. Treatment with moderate doses of interferon (10(4) units, five times weekly for 8 weeks) did not depress murine leukemia virus gp69/71 levels in serum and spleen, nor p30 levels in the spleen. Interferon given at 10(5.1) units (three times weekly for 37 weeks) caused an increased incidence of anti-erythrocyte antibodies in New Zealand Black mice. Finally, the hybrid mice given interferon at 10(6.0) units (three times weekly for 33 weeks) had increased renal immune complex deposits and increased incidences of proteinuria and anemia.

Anemia, Hemolytic↗
PubMed1978

In vitro cultivation of human tumor tissues. II. Morphological and virological characterization of three cell lines.

Nineteen human tumors, mostly of sarcomatous nature, were cultured in vitro. Three cell lines were isolated and further characterized: MG-57 derived from a giant cell tumor, MG-63 derived from an osteosarcoma and MG-72 derived from a xanthohistiocytoma. The cell lines varied in morphology and growth pattern. An abnormal karyotype with marker chromosomes was present in Mg-63 and MG-72. None of the cell lines spontaneously produced detectable C-type virus particles. Stimulation with IUDR and dexamethasone also failed to induce detectable particle release.

Animals↗
PubMed1977

Analysis of murine C-type virus structural proteins by rocket and crossed immunoelectrophoresis.

We have examined the structural proteins of Rauscher murine leukemia virus (R-MuLV) by means of rocket immunoelectrophoresis and crossed immunoelectrophoresis, using polyspecific antisera to Tween/ether-disrupted purified R-MuLV. Fifteen different precipitation lines were recognized in virus lysates. Using five reference antisera prepared to purified R-MuLV-structural proteins, the precipitation lines of p 10, p 15, p 30 and gp 69/70 were identified. These techniques, although less sensitive than radioimmunoassay, have several advantages, such as simplicity, direct control of precipitation reactions and possibility of using crude antigen preparations.

Animals↗
PubMed1977

Induction of interferon in human lymphoblastoid cells by Sendai and measles viruses.

Sendai and measles viruses were tested for their interferon-induced capacity in human lymphoblast cells. Sendai virus reproducibly induced considerable amounts of interferon (I research reference interferon unit/10(3) cells), but no increase in infectious virus titre was observed. Two Edmonston-Enders strains of measles virus grew very well. The attenuated (A) strain was a good interferon inducer (4 units/10(3) cells), while the virulent (V) strain induced only minimal amounts at a high multiplicity of infection. Pre-treatment of the cells with 5-iododeoxyuridine (IdUrd) had no effect on the growth of Sendai or EE measles virus and on interferon yields induced by Sendai virus. It slightly potentiated interferon induction by EE measles virus. Partial u.v.-light-inactivation of Sendai virus infectivity resulted in a parallel loss in interferon-inducing capacity.

Cell Count↗
PubMed1977

Synthesis and cleavage processing of oncornavirus proteins during interferon inhibition of virus particle release.

The effect of interferon on the rate of synthesis and the cleavage processing of viral proteins in mouse cells, chronically infected with Rauscher murine leukemia virus, has been studied by immunoprecipitation of newly synthesized viral proteins from virus-infected cells pulse-labeled with [35S]methionine. Immuno-precipitated, labeled polypeptides were resolved by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and then examined by autoradiography. Cleavage processing was studied in the same manner with cells that had been pulse-labeled and then incubated with non-radioactive media for a sufficient time to allow normal cleavage processing to occur. At a concentration that strongly inhibited the release of virus particles, interferon had no effect on the synthesis of proteins carrying antigenic determinants of the major core protein p30 or of the envelope glycoprotein gp69/71. Nor did it affect the post-translational cleavage processing of the precursors to these proteins. Similarly, interferon did not affect labeling or chasing of precursor protein carrying the p15 determinants; labeling of p15 itself could not be studied because it does not contain methionine.

Animals↗