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J M Pleau

Publications and source records attributed to J M Pleau.

At least 19 recordsLinked to original sources
PubMed1995

Prevention of autoimmune diabetes in nonobese diabetic female mice by treatment with recombinant glutamic acid decarboxylase (GAD 65).

The nonobese diabetic (NOD) mouse spontaneously develops insulin-dependent diabetes (IDDM or type I diabetes), resulting from T-lymphocyte-mediated destruction of pancreatic beta cells. This autoimmune phenomenon includes mononuclear cell infiltration of the islets of Langerhans (insulitis) and the presence of circulating autoantibodies. The specificity of the autoantibodies and of the autoreactive T cells was investigated and several autoantigens were proposed, in particular glutamic acid decarboxylase (GAD). This enzyme exists in two forms (GAD 65 and GAD 67) encoded by two independent genes. To explain the role of GAD in type I diabetes, we prepared recombinant rat GAD 65 as fusion protein, produced in an Escherichia coli expression system, and we treated NOD female mice from 4 to 7 weeks of age by repeated intraperitoneal injections of 5 micrograms fusion protein (3 injections per week); control groups received the fusion partner, maltose binding protein (MBP) or dissolving agent (NaCl 0.9%). We investigated two parameters, the degree of insulitis 5 weeks after the last injection and the overall incidence of the disease. Histological examination of the pancreata from GAD-treated mice revealed a significant reduction in the severity of insulitis compared with the two control groups. Furthermore, we observed that the time of onset and the frequency of diabetes in NOD females injected with GAD fusion protein differed significantly from the control groups receiving MBP or NaCl (P < 0.0001). These results show that a 3-week treatment of NOD female mice starting at 4 weeks of age protects them from diabetes, again emphasizing the crucial role of GAD as autoantigen in type I diabetes.

ATP-Binding Cassette Transporters↗
PubMed1990

A new radioimmunoassay for the thymic peptide thymulin, and its application for measuring thymulin in blood samples.

A new, specific and sensitive radioimmunoassay, using a polyclonal antiserum raised in rabbits, is described for quantitating plasma thymulin. As little as 300 fg thymulin can be measured in one assay tube. The method has been used to measure thymulin in human blood (umbilical vessel blood, 2191 +/- 123 fg/ml; children and adults up to the age of 20 years, 1499 +/- 119 fg/ml; and adults between 21-65 years, 371 +/- 18 fg/ml). There is a highly significant decrease within these three groups (P less than 0.001 by one way analysis of variance). Also plasma thymulin levels were determined in rats (601 +/- 127 fg/ml) and in pooled plasma samples from mice (638 +/- 56 fg/ml). No thymulin was detected in plasma obtained from nude rats, nude mice and thymectomised mice. These results show that the radioimmunoassay described here is a useful quantitative tool for measuring plasma thymulin that will have applications in basic, applied and clinical research.

Animals↗
PubMed1985

Thymulin.

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Animals↗
PubMed1984

Studies on the zinc binding site to the serum thymic factor.

Gel filtration studies of 65Zn2+ binding to thymulin show that the nonapeptide can strongly bind one zinc metal ion. At pH 7.5, thymulin binds one zinc ion with an apparent affinity constant Kd of 5 +/- 2 X 10(-7) M. Binding is pH dependent. No binding is observed below pH 6.0. Ga3+, Al3+, Mn2+ and Cu2+ can compete with the binding of Zn2+ at pH 7.5. A good correlation between the competition potencies of metal ions used and the extent of biological activity of thymulin in the presence of these metal ions in an in vitro rosette assay is observed. Structural analogs of thymulin and non-thymulin-related peptides were used in a gel filtration technique to tentatively define the nature of amino acids present in the Zn2+-binding site of thymulin.

Binding Sites↗
PubMed1983

Interaction of thymopoietin peptides with the specific receptor of facteur thymique serique (FTS).

The capacity of ubiquitin (UB) and thymopoietin II (TP) related peptides (TP 5 and TP 13) to interfere with the specific binding of [3H]FTS on intact 1301 cells or on 1301 plasma membrane preparations was studied. All 3 peptides significantly inhibited the binding of [3H]FTS to its receptors on intact 1301 cells at concentrations 20 to 100 times higher than FTS itself. Conversely, none of the 3 peptides provided a significant inhibition of the specific [3H]FTS binding to plasma membrane preparations of 1301 cells compared to control peptides. These contrasted results suggest that TP-related peptides and, to a lesser degree, UB may share the same target cells with FTS and interfere with FTS effects on T cells, but this interaction probably does not involve direct high affinity binding to the FTS receptors.

Animals↗
PubMed1982

High affinity binding sites on plasma membrane obtained from the lymphoblastoid cultured 1301 cell line for highly radioactive serum thymic factor.

The interaction of the synthetic serum thymic factor (FTS, facteur thymique sérique) with a plasma membrane preparation of human T lymphocytes from the lymphoblastoid T cell line 1301 was studied using 3H-labelled FTS (specific activity 120 Ci/mmol). The binding is temperature dependent and function of the concentration of both 3H-labelled FTS and membrane proteins. At 37 degrees C, using 1 nM of 3H-labelled FTS as steady state is observed within 80 min. The binding is reversible, specific and saturable. Scatchard analysis reveals the existence of at least two binding sites with respective Kd of the order of 0.516 +/- 0.2 nM and 110 +/- 27.8 nM with concentration of 0.186 +/- 0.045 pmol and 2.026 +/- 0.367 pmol per mg of membrane protein.

Binding Sites↗
PubMed1982

Monoclonal antibody against the serum thymic factor (FTS).

Hybrid cell lines secreting antibodies specific for synthetic serum thymic factor (FTS) were prepared by cell fusion and cloning techniques. Spleen cells from BALB/c mice immunized with BSA-coupled FTS were fused with P3-x63-Ag8.653 myeloma cells. Antibodies produced by these hybrids were screened in vitro for their ability to absorb the activity of synthetic FTS in a rosette assay and in vivo for their capacity to induce the disappearance of endogenous FTS. Subsequently, the clones selected were transferred intraperitoneally into BALB/c mice. Ascitic fluid was produced and used as a source of antibody. The monoclonal antibody was shown to bind specifically to thymic reticulo-epithelial cells, using an indirect immunofluorescence technique. Furthermore, once injected into normal mice, the antibody induced the disappearance of FTS from the serum and modified the azathioprine sensitivity of spleen rosette-forming cells for more than 3 weeks.

Animals↗
PubMed1982

Identification of FTS (facteur thymique serique) on thymus ultrathin sections using monoclonal antibodies.

Using a new immunoelectromicroscopical technique, this study confirms the localization of the 'facteur thymique sérique' (FTS) in the reticulo-epithelial cells of mouse thymus. The use of anti-FTS monoclonal antibodies on ultrathin sections for electron microscopy reveals FTS in cytoplasmic vacuoles, labelling density depending on the density of the vacuolar content. The successful application of this technique opens the way to its use for double-immunolabelling.

Animals↗
PubMed1982

Location of FTS (facteur thymique sérique) in the thymus of normal and auto-immune mice.

This study was concerned with the in situ localization of facteur thymique sérique (FTS) by immunoelectron microscopy in the thymus of normal C57BL mice and aged auto-immune SWAN mice. Normal young mice have anti-FTS antibodies fixed specifically on the floccular material present in the cytoplasmic vacuoles of epithelial cortical and medullary cells. In aged auto-immune SWAN mice the anti-FTS antibodies show an activity only in the granules present in the vacuoles or free in the cytoplasm of epithelial cells. The floccular material is not labelled by the same antibodies. FTS positive granules show a repetitive structure which is characteristic of crystalline protein formations. The presence of FTS in the granules of cells confirm the hypothesis of FTS storage in the cytoplasm of epithelial cells in vivo during the auto-immune process.

Animals↗
PubMed1981

[Modification of the antigenicity of the serum thymic factor (thymulin) by zinc].

We have previously reported that the serum thymic factor (FTS) exists under two forms, one deprived of zinc, biologically inactive and another one containing zinc, biologically active for which we have proposed the name of thymulin (FTS-Zn). A new iodinated tracer (125I FTS-Zn) has been prepared by fixing zinc on synthetic FTS. This tracer is recognized by a Rabbit anti-FTS antiserum at a 1/20,000 dilution. Normal Mouse sera displace the binding of FTS-Zn to the antiserum (40-60% inhibition) whereas thymectomized mouse sera have no effect. These results should allow the establishment of a simple radioimmunoassay for thymulin (FTS-Zn) present in biological fluids.

Animals↗
PubMed1981

[Role of zinc and other metals in the biological activity of the serum thymic factor (thymulin)].

The serum thymic factor (FTS) used in synthetic or natural form, loses its biological activity after passage on a chelating agent, Chelex 100. Such activity is recovered after addition of zinc and, to a lesser degree, of certain other metals. FTS activation is secondary to zinc binding to the peptide. These results indicate the existence of two FTS forms: the first one, deprived of zinc and biologically inactive, the second one containing zinc and biologically active, for which we purpose to coin the name of thymulin.

Animals↗
PubMed1980

Cytoplasmic localization of FTS (facteur thymique sérique) in thymic epithelial cells. An immunoelectronmicroscopical study.

This study was concerned with the localization of the facteur thymique sérique (FTS) by immunoelectronmicroscopy in cultured thymic epithelial cells. The FTS antibodies labelled differently sized cytoplasmic vacuoles containing a substance of variable density. This substance occurs occasionally in crystalline structures which reacted strongly with purified FTS antibodies. On the ultrastructural level the FTS-positive cells were demonstrated to fix specifically keratin antibodies and to contain tonofilaments. Some of these cells originated from the thymic medulla proved by the presence of microvilli-forming cytoplasmic vacuoles. The existence of FTS-positive crystalline inclusions confirmed the hypothesis of a storage process in the cytoplasm of thymic epithelial cells in vitro or in pathological conditions.

Animals↗
PubMed1977

Structural study of circulating thymic factor: a peptide isolated from pig serum. I. Isolation and purification.

A circulating thymic factor (FTS) has been characterized by a bioassay based on its ability to render theta-negative rosette-forming cells theta-positive and azathioprine-sensitive. FTS was sequentially purified and finally isolated from 1000 liters of pig serum by ultrafiltration, gel filtration, and ion exchange chromatography. Its amino acid composition and apparent molecular weight estimated by Sephadex G-25 chromatography, indicate that FTS is a nonapeptide of composition lysine, aspartic acid (or asparagine), serine 2, glutamic acid (or glutamine) 2, glycine 2, and alanine.

Amino Acids↗
PubMed1977

Structural study of circulating thymic factor: a peptide isolated from pig serum. II. Amino acid sequence.

The amino acid sequence of a circulating thymic factor (FTS, facteur thymique sérique) isolated from pig serum has been established as less than Glu-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn-OH. This sequence was obtained by Edman analysis both on the intact peptide and after tryptic digestion. The COOH-terminal residue was identified by carboxypeptidase A digestion. A synthetic peptide was prepared which showed the same biological activities as native pig circulating thymic factor, thus confirming the proposed primary structure.

Amino Acid Sequence↗
PubMed1977

[De novo purine biosynthesis. In vitro measurement in hyperuricemia (author's transl)].

De novo purine biosynthesis has been investigated in circulating blood lymphocytes in vitro. N-formyl-glycinamide ribonucleotide (FGAR) has been mesured using 14C-formate incorporation in the presence of azaserine, a metabolic inhibitor blocking the metabolical pathway at the level of FGAR synthesis. Such a synthesis was measured in 20 healthy controls, 24 patients with primary gout (11 on allopurinol therapy) and 26 patients with chronic renal failure and secondary hyperuricemia (8 on allopurinol therapy). Among gouty patients without allopurinol therapy, FGAR synthesis was normal in 5 and increased in the others. FGAR synthesis was decreased in patients with renal failure whatever the therapy. However, FGAR synthesis remained increased in patients with a primary gout complicated with renal insufficiency. The test we propose for de novo purine biosynthesis measurement is simple and of value to analyse the patho-physiology of hyperuricemia and its therapy. The test allows an acurate discrimination between primary and secondary hyperuricemia in the presence of renal insufficiency.

Adult↗