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Biomedical subjects

M Aguet

Publications and source records attributed to M Aguet.

At least 91 records · Page 5Linked to original sources
PubMed1986

[Circulating interferon in patients with systemic lupus erythematosus. A prospective study].

The serum levels of interferon (IFN) were measured in 31 patients with systemic lupus erythematosus (SLE). Among the 31 patients, 8 (25%) showed IFN in the sera: in 4 patients IFN titers of 16 U/ml, and in the other 4 patients titers of greater than or equal to 32 U/ml became detectable. Whereas antibodies to native DNA (nDNA) were present in 6 of the 8 IFN positive patients, anti-nDNA antibodies were only positive in 6 of the 23 IFN negative individuals (p less than 0.002). Eight months after the first search for IFN in the patients' sera, 6 of the 8 IFN positive patients showed reduced IFN serum levels and one each had an increased or stable IFN titer. A good correlation between IFN titers and both the anti-nDNA antibody titers and the disease activity was observed. However, there were patients with active disease, high anti-nDNA titers but no IFN in the serum.

Adult↗
PubMed1986

A monoclonal antibody against altered LFA-1 induces proliferation and lymphokine release of cloned T cells.

A murine monoclonal antibody (I-17, IgM) has the following functional effects on murine long-term T cell clones: inhibition of cell-mediated lysis, induction of proliferation, release of lymphokines and change of the cell morphology. The determinant detected by I-17 is expressed on long-term T lines but not on thymocytes, lymph node cells and spleen cells. I-17 precipitated proteins with apparent molecular mass of 220 kDa, 170 kDa, 150 kDa and 100 kDa. Biochemical studies indicate that the determinant recognized by I-17 is tunicamycin sensitive and that I-17 binds to the alpha chain of the lymphocyte function-associated antigen (LFA-1).

Animals↗
PubMed1986

Treatment of hairy cell leukemia with recombinant alpha interferon: II. In vivo down-regulation of alpha interferon receptors on tumor cells.

Interferons (IFNs) initiate their effects by interacting with specific high-affinity cell surface receptors, but little is known about the physiology of IFN receptor interaction in vivo. Treatment of patients suffering from hairy cell leukemia (HCL) with human recombinant alpha IFN results in significant tumor regression, with clinical improvement in a high percentage of cases. To investigate a possible relevance of binding parameters as response markers, IFN receptor interaction on tumor cells responsive to IFN in vivo was studied. Binding of human alpha 2 IFN to circulating hairy cells was analyzed before and during IFN therapy in ten patients selected on the basis of high numbers of peripheral hairy cells. Binding experiments were carried out on Ficoll-Paque fractionated peripheral cell samples containing a majority of hairy cells. All patients reacted to recombinant alpha IFN treatment with a striking decrease in binding capacity within 12 hours after the first injection. As demonstrated by using a monoclonal antibody able to recognize alpha 2 IFN bound to its receptor, this decreased binding capacity was not due to blocking by circulating IFN but rather to a decrease in receptor number. This receptor "down-regulation" was partially reversible after the first IFN injection. However, upon prolonged IFN therapy, all patients displayed a stable state of decreased receptor expression. Down-regulation of IFN receptors can be regarded as a response marker to IFN treatment. This response marker, however, was not correlated with the clinical response within the first months of IFN therapy.

Animals↗
PubMed1986

Treatment of hairy cell leukemia with recombinant alpha interferon: I. Quantitative study of bone marrow changes during the first months of treatment.

Seventeen patients with hairy cell leukemia (HCL) were treated with low doses of recombinant alpha interferon (IFN) for over 4 months. Marked improvement was observed in peripheral blood and bone marrow in 15 of 17 patients. Comparison of pretreatment values and hemograms obtained after 4 months of treatment showed a marked decrease in circulating hairy cells (P less than .01), a decrease in the number of lymphocytes (P less than .01), a rise in the number of platelets (P less than .05), granulocytes (P less than .05), and monocytes (P less than .01), and a rise in the hemoglobin level (P less than .01). Transient reduction in the number of granulocytes was noted during the first month. Correction of thrombocytopenia often appeared within 2 months and usually preceded improvement of anemia, monocytopenia, and neutropenia. Bone marrow biopsy specimens were taken before treatment and 2, 4, and 7 months after its initiation. The volumes occupied by hairy cells, cells of the myeloid lines, and adipocytes were studied by stereological analysis of semithin sections. Decrease in the volume occupied by hairy cells was seen after 4 months of treatment (P less than .01), and the volume continued to decrease at the seventh month (P less than .05). Hairy cells were no longer detected on bone marrow biopsies of 4 of 17 patients by the fourth month and in 3 of 8 additional patients by the seventh month. A rise in the volume occupied by normal myeloid cells was visible by the second month of treatment (P less than .01). Nevertheless, the volume occupied by granulocytes remained lower than in the normal controls (P less than .01). After an initial increase during the first 2 months of treatment (P less than .01), the overall cellularity remained unchanged at 4 months and decreased significantly (P less than .05) at 7 months. Except for biopsies at 2 months, mean cellularity was below that of control biopsies (P less than .01).

Biopsy↗
PubMed1985

A crystalline synthetic peptide representing the epitope of a monoclonal antibody raised against synthetic interferon-alpha 1 fragment 111-166.

The antigenic determinant recognized by the monoclonal antibody that had been raised against synthetic human interferon-alpha 1 (IFN-alpha 1) fragment 111-166 [Arnheiter, H., Thomas, R.M., Leist, T., Fountoulakis, M., and Gutte, B. (1981) Nature (Lond.) 294, 278-280] and that cross-reacted with human IFN-alpha 1, IFN-alpha 2, and IFN-alpha A made in Escherichia coli, was localized to the region between residues 151 and 166 using synthetic COOH-terminal interferon fragments. In solid-phase radioimmunoassays neither the strongly hydrophilic COOH-terminal nonapeptide IFN 158-166 nor its mixtures with IFN 151-162 or IFN 149-158 showed any measurable interaction with the antigen binding site of the monoclonal antibody. For antibody binding, the full covalent structure of IFN 151-166 was required. Quantitatively very similar results were obtained with IFN 149-166 and IFN 143-166. The synthetic COOH-terminal hexadecapeptide of human IFN-alpha 1 (IFN 151-166) could be crystallized.

Antibodies, Monoclonal↗
PubMed1985

Receptor dynamics of closely related ligands: "fast' and "slow' interferons.

Two related human alpha interferons with 83% homology in their primary sequences show a similar specific activity on nonhuman cells, but a striking difference on human cells, on which alpha-1 shows 1-5% of the specific molar activity displayed by alpha-2. Both interferons were labelled with 125I, and their binding kinetics followed on growing cultures of the human Burkitt line Daudi. Binding of alpha-1 showed slower rates of association and faster rates of dissociation implying that differences in apparent binding affinity were responsible for the differences in specific molar activity. However, binding was shown to reach steady-state rather than an equilibrium, so differences in the dynamics of the ligand-receptor complexes may represent amplification of differences in the initial binding constant. alpha-2, but not alpha-1, induces a marked loss of binding sites leading to a high affinity steady-state binding. Inhibition of cell multiplication by both interferons depends on a continued stimulation by free ligands at steady-state. It is proposed that the differences in specific molar activity are, in the main, kinetic and cause alpha-1 and alpha-2 to behave respectively as "slow' and "fast' interferons.

Animals↗
PubMed1985

125I-labelled human interferons alpha, beta and gamma: comparative receptor-binding data.

Binding of 125I-labelled human recombinant DNA interferons (IFNs) alpha-2, beta and gamma was compared on various human lymphoid cells and embryonic fibroblasts. While binding constants were within an order of magnitude for all three interferons (10(-10) to 10(-9) M), no competition was observed between IFN-gamma on the one hand and IFN-alpha 2 and IFN-beta on the other. However, consistent with previous reports, IFN-alpha 2 and IFN-beta competed for presumably common receptors. Depending on the cell type, binding sites for IFN-gamma were expressed in different numbers compared to those for IFN-alpha 2 and IFN-beta. These direct comparative binding studies support the hypothesis that the receptor system for IFN-gamma is unrelated to the IFN-alpha/beta system.

Binding Sites↗
PubMed1984

Various human interferon alpha subclasses cross-react with common receptors: their binding affinities correlate with their specific biological activities.

Seven different human interferon (IFN) alpha subtypes were compared with regard to competitive inhibition of specific high-affinity binding of 125I-labeled IFN alpha-2 to human and bovine cells. All IFNs tested (alpha-1, -2, -4, -5, -6, -7, -8) competed for common binding sites. Marked differences in the binding affinities were observed between IFN alpha-1 and IFN alpha-2. The binding affinities of the various subtypes correlated with the respective specific biological activities determined in an antiviral assay. These observations suggest that at least some biological effects of IFNs are initiated by receptor activation and depend quantitatively on the degree of receptor saturation.

Animals↗
PubMed1984

[Interferon production in acute virus hepatitis].

Serum interferon activity was measured in 40 patients with acute viral hepatitis A, B and non-A-non-B during the acute stage of the disease and correlated with the severity, the long-term outcome and the viral etiology of the disease. Patients with alcoholic hepatitis, patients with an influenza-like illness and healthy volunteers served as controls. 80% of all patients with virus hepatitis revealed no measureable or only borderline interferon activity in their serum. No correlation was found with severity and long-term outcome of the disease, but patients with virus hepatitis A showed a stronger interferon induction than patients with hepatitis B and non-A-non-B. Further investigations of the interferon system in patients with virus hepatitis might help to improve our understanding of the different forms of the disease. The data presently available, however, do not permit as yet to define the value of interferon in the treatment of severe forms of acute virus hepatitis.

Hepatitis A↗
PubMed1982

Antigenic correlations between components of C243 and L cell interferons.

The three components of virus-induced interferon (IFN) from C243 cells, with molecular weights of 19,000, 24,000 and 30,000, were examined for neutralization by antisera against the alpha (24,000) and beta (36,000) types of virus-induced L cell IFN. The results indicated that the C243 19,000 component belongs to the alpha type, and the 24,000 and 30,000 components to the beta type. The 19,000 component was also indistinguishable from L cell IFN-alpha in the reaction with antisera against human IFN-alpha.

Animals↗
PubMed1982

Prevention of interferon-induced augmentation of cellular antitumor effector mechanisms by phorbol esters.

Both natural killer cell- and macrophage-mediated spontaneous in vitro cytotoxicity for tumor targets is rapidly and strongly augmented by interferon. Macrophage-activating lymphokines considerably enhance macrophage-tumoricidal activity but did not affect natural killer cell-type cytotoxicity. Augmentation of cytolytic capacity by interferon and by macrophage-activating lymphokines is prevented by the tumor-promoting phorbol ester, 12-O-tetradecanoylphorbol-13-acetate. However, the classical antiviral activity and the specific binding of interferon to cell surface receptors remains unaffected by 12-O-tetradecanoylphorbol-13-acetate.

Animals↗
PubMed1981

Binding of 125I-labelled human alpha interferon to human lymphoid cells.

To investigate the binding of interferon to human lymphoid cells, we purified human alpha interferon and radio-labelled it with iodine-125. Binding at 4 degrees C could be saturated and was inhibited by unlabelled interferon; it was specific for cells of human origin. Dissociation constants for the complex of interferon and receptor site were of the order 10(-9)-10(-11) M. All human cells tested showed such binding. Occupation of these high-affinity sites, at 37 degrees C, was compared with the inhibition of cellular growth due to interferon. The most sensitive cell line (Daudi) gave a complete biological response with only a fraction of its sites occupied. Evidence of two sites was found for a line (P3HRI) showing intermediate sensitivity. A relatively insensitive line (Raji) showed no response when all its high-affinity sites were occupied.

Cell Line↗
PubMed1981

Enhancement of Fc gamma receptor expression in interferon-treated mice.

Treatment of C3H mice with partially purified or highly purified virus-induced interferon resulted in a marked increase in the expression of Fcgamma receptors (Fcgamma R) on splenic lymphocytes, mesenteric lymph node cells and thymocytes from cortisone-treated mice. An increase on Fcgamma R on splenic lymphocytes was seen as early as 5 h and lasted at least 72 h after a single injection of interferon. We suggest that enhancement of Fcgamma R is one of the mechanisms by which interferon exerts some immunostimulating effects in vivo.

Animals↗