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Biomedical subjects

C Vincent

Publications and source records attributed to C Vincent.

At least 271 records · Page 15Linked to original sources

Serum beta-2-microglobulin binding activity in monoclonal gammopathy: correlative study and clinical significance.

Serum beta 2m binding activity (S beta 2m-BA) was determined by a polyethylene glycol exclusion test of radiolabeled human beta 2m in 185 serum samples from 62 patients with multiple myeloma (MM). Elevated S beta 2m-BA was found in more than half of the samples from IgG myeloma taken before treatment or during progression of the disease but not during the plateau-phase. Conversely, elevated S beta 2m-BA was found in only one case of IgA myeloma, one case of monoclonal gammopathy of undetermined significance and none of the Bence Jones myelomas. S beta 2m-BA appears to be related to disease progression in IgG myeloma. The activity is supported by minute amounts of serum autoantibodies which are distinct from the monoclonal component. S beta 2m-BA was independent from serum beta 2m levels.

Adult↗

Fluorescence study of human beta 2 microglobulin.

A fluorescence study human beta 2 microglobulin showed the existence of two types of Trp residues, one quite exposed to the solvent, the other buried in a hydrophobic environment. The change in excitation wavelength made obvious the existence of a Tyr to Trp energy transfer mechanism. Treatment by urea or guanidine chlorhydrate brought about quite different results. With the former denaturing agent, some Trp residues remained buried; with the latter, the protein was completely unfolded, as proved by iodide quenching. pH variations could not unfold beta 2m enough to convert all Trp residues to exposed ones. When heated, beta 2m supported a transition that began at 50 degrees (melting temperature 63 degrees) and was not reversible. All these results suggest a rather compact conformation as in a globular protein.

Beta-Globulins↗

Characterization of polyclonal autoantibodies specific for beta 2-microglobulin in multiple myeloma sera.

Among 185 sera from 62 patients with multiple myeloma, two serum samples with high beta 2-microglobulin (beta 2m) binding activity (S beta 2m-BA) were investigated. The S beta 2m-BA was shown to be distinct from the monoclonal component and to be represented by autoantibody of the IgG class. These antibodies were specific for beta 2m. They formed macromolecular complexes with beta 2m, indicating that at least two distinct epitopes of beta 2m can be recognized by these antibody molecules. The association-dissociation constants and antigen binding capacities of these autoantibodies were compared with that of monoclonal or polyclonal heterologous antibodies.

Aged↗

Synthesis of 8-(2-4 dinitrophenyl 2-6 aminohexyl) amino-adenosine 5' triphosphate: biological properties and potential uses.

We have synthetised 8-(2-4 dinitrophenyl 2-6 aminohexyl) amino-adenosine 5' triphosphate (in short : rATP-DNP), a derivative of ATP which carries a dinitrophenyl group. We show that rATP-DNP is a substrate for calf thymus deoxynucleotidyl terminal transferase (EC 2.7.7.31) and E. coli DNA polymerase I (Kornberg polymerase EC 2.7.7.7.). It can therefore be incorporated into DNA molecules by elongation from 3' ends or by nick translation. The incorporated dinitrophenyl group can be recognized by specific antibodies which can then be detected by anti-antibodies coupled to an enzyme. DNP groups could also be introduced into DNA after enzymatic incorporation of 8-aminohexyl adenosine 5' triphosphate and reaction with 1-fluoro-2-4-dinitrobenzene. Thus, DNA molecules carrying DNP groups can ultimately be revealed by enzymatic coloured reactions. Potential uses of this enzymatic labelling as a substitute to the radioactive detection of nucleic acids, are discussed.

Adenosine Triphosphate↗

Turnover studies of human beta 2-microglobulin in the rat: evidence for a beta 2-microglobulin-binding plasma protein.

1. 125I-labelled beta 2-microglobulin (beta 2m) was injected into rats and protein or non protein-bound radioactivity was determined in plasma urine and several organs. 2. The observed kinetics differed from those expected according to the bicompartmental model for plasma protein turnover. The difference was attributed to the binding of a part of the tracer to a plasma component. Chromatography of plasma taken after injection of beta 2m showed an additional peak of radioactivity at the 55,000-80,000 daltons position. 3. In animals with ligated renal arteries, disappearance of the tracer from the plasma was markedly prolonged, and little non-protein-bound radioactivity was detectable in plasma, indicating that the kidney was the major site of catabolism of beta 2m. 4. Chromatography of plasma from control rats and rats with ligated renal arteries showed that the kidney was the major site of catabolism for free beta 2m only. 5. In normal rats, the urine was found to contain only non-protein-bound radioactivity.

Animals↗

Effects of N-alkylation and n-acylation on tobramycin activity.

The activities of tobramycin derivatives acetylated and ethylated on the 6'-N,2'-N and 3-N positions were examined. The MICs of these derivatives against tobramycin sensitive strains indicated that 2'-N-ethylated and 6'-N-ethylated derivatives have a fairly good activity, and confirmed that the 3-N position is the most important one for antibiotic activity since 3-N derivatives were less active. The MICs of these derivatives against tobramycin resistant strains, and their inactivation by tobramycin modifying enzymes were examined. These results showed that 2'-N or 6'-N ethylation protects the drug against inactivation by AAC(2') or AAC(6'), respectively, and 2'-N-ethyltobramycin and 6'-N-ethyltobramycin were active against strains containing these modifying enzymes. On the other hand, 3-N ethylation protects the drug against inactivation by AAC(3) but 3-N-ethyl tobramycin does not inhibit strains containing this enzyme.

Acylation↗

beta 2-Microglobulin and beta 2-microglobulin-binding proteins in inflammatory diseases.

Beta 2 microglobulin (beta 2m) is a 11,800 daltons polypeptide non covalently associated with the heavy chain of class I histocompatibility antigens (HLA-A, B and C) at the surface of nearly all cells. Serum beta 2m levels are passively controlled by the glomerular filtration rate. Increased beta 2m production resulting in elevated serum levels despite normal renal function have been reported in malignancies of the lymphoreticular system (e.g. multiple myeloma) and in various autoimmune or chronic inflammatory diseases, including rheumatoid arthritis. In some situations beta 2m levels were shown to be positively correlated with absolute lymphocyte counts in the peripheral blood or with the score of mononuclear cell infiltrates in biopsy specimens. Together with the demonstration that activated T lymphocytes release beta 2m in culture, these data support the hypothesis that increased production of beta 2m in vivo could represent a non specific indication of lymphocyte activation. Follow-up studies of individual patients are needed to define the clinical situations in which beta 2m determination may improve the immunological monitoring, with special reference to the early diagnosis of relapses and the assessment of individual response to treatment.

Arthritis, Rheumatoid↗

[Presence of glycoproteins binding human beta 2 microglobulin in rat serum].

125I-labeled human beta 2 microglobulin forms complexes with Rat serum glycoproteins. After beta 2m injection in vivo, the serum contains a complex in a 55 K-67 K position. When incubated with Rat serum vitro beta 2m forms additional complexes in greater than or equal to 200 K position. The 55 K complex is partially precipitated by Brown-Norway anti-Lewis alloantiserum.

Animals↗

Elevation of serum beta 2 microglobulin in liver diseases.

beta 2 Microglobulin levels were measured by radioimmunoassay in the serum of 160 patients with liver disease and compared to 63 normal controls and 75 asymptomatic HBs-Ag carriers. All the latter subjects had normal values. Elevated serum beta 2 microglobulin levels were found in most of the other categories: acute viral hepatitis (35/45); chronic persistent (8/26) or active (35/41) hepatitis and liver cirrhosis (27/38). beta 2 Microglobulin values were significantly lower in chronic persistent hepatitis than in the three other groups (p less than 0.05). Steroid therapy was followed by reduction of serum beta 2m levels in 11/11 cases of chronic active hepatitis, eight of whom returned to normal value. Although linked to the course of the disease, variations of beta 2 microglobulin were independent of transaminases, bilirubin and gamma globulins. Elevated serum beta 2 microglobulin correlated with demonstration of rheumatoid factor but not with detection of circulating immune complexes, hepatitis B virus markers or autoantibodies. The results suggest that elevation of serum beta w microglobulin is encountered mostly in the active forms of inflammatory liver diseases.

Adolescent↗

Tentative identification of a second central nervous system myelin membrane autoantigen (M2) by a biochemical comparison with the basic protein (BP).

Two central nervous system myelin autoantigens, M2 and basic protein (BP), were examined, using complement-fixing antibodies against each autoantigen as markers on myelin. M2 activity was very labile and very insoluble, PB activity was very resistant. Trypsin reduced both activities an this reduction was greater after phospholipase treatment. Both activities were slightly solubilized in 8 M urea. It is known that BP is not present on the surface of myelin and is considered a peripheral membrane protein. M2 appears to be a surface and integral membrane protein, and as such resembles Folch Pi proteolipid protein. The relationship between M2 and BP requires further study.

Animals↗

A sandwich method of enzyme immunoassay. III. Assay for human beta-2 microglobulin compared with radioimmunoassay.

A sandwich enzyme immunoassay has been developed to measure human beta-2 microglobulin (beta 2m) in bilogical fluids. beta 2m is first bound by specific antibody covalently coupled to microcrystalline cellulose. The solid phase is washed and reincubated with glucose oxidase-labeled anti-beta 2m antibody. After washing, the enzymic activity of the solid phase is measured by incubation with the appropriate chromogenic substrate. The OD is directly related to the quantity of beta 2m to be measured. A second sandwich assay has also been developed which uses plastic microplates coated with the IgG fraction of rabbit anti-beta 2m serum. Reproducible results are obtained in the range 2-150 and 0.75-48 microgram/l respectively. These tests detect 17 fmoles of beta 2m. Assays of 27 sera showed good agreement between these two enzyme immunoassay methods and two radioimmunoassays.

Beta-Globulins↗

A two-step synthesis of new water-soluble polymers of NAD+ and ADP. The biological properties of these polymers.

Alkylation at the N-1 position of the adenine moiety of NAD+, ADP or ATP with 2,3-epoxypropyl acrylate, followed by polymerization with or without acrylamide at pH 8, gave water-soluble polymers of NAD+ and ADP where the alkyl chain was located at the exocyclic adenine C-6 amino group. Cofactor incorporations were good to high: 145-447 mumol NAD+/g polymer and 667 mumol ADP/g polymer. About 30% of the bound NAD+ could be reduced with rabbit muscle lactae dehydrogenase, yeast alcohol dehydrogenase and Bacillus subtilis alanine dehydrogenase; 84% of the bound ADP was phosphorylated with rabbit muscle creatine kinase. High cofactor activities were obtained with polymerized NAD+ with alcohol dehydrogenase as enzyme: the initial rate of NAD+ polymer reduction was 35-81% that of free NAD+. These values remained substantially high with agarose-immobilized alcohol dehydrogenase (15-36%) and should eventually allow their use in continuous enzymatic reactors. Enzymatic phosphorylation of ADP polymer by creatine kinase gave an ATP polymer with high biological activity: 480 mumol ATP/g polymer were transformed with yeast hexokinase.

Acrylic Resins↗