Biomedical subjects

M Daveau

Publications and source records attributed to M Daveau.

At least 55 records · Page 3Linked to original sources

PubMed1988

The synthesis of human alpha-2-HS glycoprotein is down-regulated by cytokines in hepatoma HepG2 cells.

The regulation of the synthesis of alpha-2-HS glycoprotein (AHSG) by inflammatory mediators from activated monocytes was studied on the human hepatoma cell line HepG2 and compared to that of albumin. Monocyte-conditioned medium, recombinant human interleukin-6 (rhIL6) and interleukin-1 beta (rhIL1 beta) all down-regulated the synthesis of AHSG. This decrease was found both at the protein and the mRNA level. The most efficient mediator was the monocyte-conditioned medium, when rhIL1 beta was found to be less efficient than rhIL6. The combination of rhIL6 and rhIL1 beta resulted in an additive down-regulation of the AHSG mRNA levels. Similar results were obtained with albumin. These data indicate that AHSG is a negative acute-phase protein whose synthesis is regulated by cytokines in a manner similar to that of albumin.

Blood Proteins↗

PubMed1988

Regulation of alpha 1-acid glycoprotein plasma concentration by sex steroids and adrenal-cortical hormones during experimental inflammation in the rat.

Treatment of adult intact rats with sex steroids (estradiol-17 beta, ethynylestradiol, dihydrotestosterone) raises the concentration of serum acute-phase alpha 1-acid glycoprotein (AGP). Estrogens are more effective than dexamethasone, and experimental inflammation causes an additive effect on AGP synthesis when ethynylestradiol is given simultaneously. Adrenaline is also able to increase the AGP level. Experiments with adrenalectomized and adrenalectomized plus castrated rats result in a 50% reduction in the serum level of AGP as compared with that in normal and hypophysectomized rats. Although ethynylestradiol is the strongest inducer of AGP synthesis in intact animals, it is unable to enhance significantly the AGP level in adrenalectomized rats, contrary to dexamethasone. Adrenalectomized rats are incapable of undergoing a substantial increase in plasma AGP level following experimental inflammation, and ethynylestradiol or adrenaline cannot take the place of dexamethasone in inducing high levels of AGP in these inflamed rats. These results indicate that glucocorticoids play an obligatory role in modulating AGP synthesis either by directly regulating the AGP gene or in modulating AGP synthesis by increasing the stability of AGP mRNA. Finally, it is suggested that glucocorticoids may also act in unmasking receptor binding sites at the AGP gene level for other mediators such as sex steroids and putative inflammatory factors.

Adrenal Cortex Hormones↗

PubMed1987

IgG (Gm) allotypes in acute measles encephalomyelitis and subacute sclerosing panencephalitis.

Gm phenotype or haplotype frequencies are known to be increased in some neurological diseases involving dysregulation(s) of the immune system. Therefore, possible associations between acute measles encephalitis (AME) or subacute sclerosing panencephalitis (SSPE) and alleles of the Gm system were investigated by comparison of children (41 AME subjects and 62 SSPE subjects) with 378 ethnically and geographically matched controls. Although the Gm3;..;11 haplotype displayed a very low frequency among SSPE children, no statistically significant departure in the distribution of Gm phenotypes could be evidenced between AME or SSPE, and controls. A further appraisal of combined Gm and HLA phenotypes may be warranted in both diseases since Gm/HLA interactions have been demonstrated in other immunopathological conditions.

Adolescent↗

PubMed1986

Biosynthesis of the third component of complement (C3) by the human monocytic-cell line U-937. Induction by phorbol myristate acetate.

Phorbol myristate acetate (PMA)-stimulated human monocyte-like cells (U-937) were found to synthesize the third component of complement (C3), as shown by enzyme-linked immunosorbent assay and immunoprecipitation from [35S]methionine-labelled culture supernatants. C3 synthesis occurred at a rate of about 160 ng of C3/24 h per 10(6) cells on day 7 after addition of PMA; it was blocked by cycloheximide treatment and was restored after removal of the inhibitor. SDS/polyacrylamide-gel-electrophoretic analysis of the immunoprecipitated protein showed that the size and subunit structure of the newly synthesized C3 were identical with those of plasma C3, and that a single-chain intracellular precursor was present in the cell lysates. Haemolytic assays showed that the synthesized C3 fully expressed functional activity in early culture within 4 h. After longer culture, a loss of haemolytic activity was observed. The possibility that newly secreted C3 is cleaved by U-937 cells themselves was suggested.

Cell Line↗

PubMed1986

Long-term biosynthesis of complement component C3 and alpha-1 acid glycoprotein by adult rat hepatocytes in a co-culture system with an epithelial liver cell-type.

We used a system of co-culture of adult rat hepatocytes with another epithelial cell type from rat liver to study the synthesis of two acute-phase reactants, alpha-1 acid glycoprotein (alpha 1AGP) and the third component of complement (C3), and we have obtained long-term secretion of these two proteins. After a period of adaptation corresponding to the first 2-4 days of the co-culture, hepatocytes secreted C3 and alpha 1AGP for at least 2 weeks at a mean level higher than that observed in the first days of a pure culture of hepatocytes. When pulse-chase analysis was performed on day 6 of co-culture, kinetics of synthesis of alpha 1AGP and C3 were the same as those observed on day 1 of a conventional culture of pure hepatocytes. Furthermore, intracellular and extracellular alpha 1AGP had Mr values respectively of 39,000 and of 42,000-52,000, identical with those observed in pure cultures of hepatocytes. Similarly, the molecular size and subunit structures of C3 were the same in co-culture and in cultures, indicating an identical processing of this protein. C3 produced in co-culture was also haemolytically active. Therefore, the system of adult hepatocytes co-cultured with this liver epithelial cell provides a physiological system in vitro which permits long-term synthesis of the two acute-phase reactants C3 and alpha 1AGP. This model opens the possibility to study the modulation of the synthesis of these two proteins during a long period by inflammatory agents or by hormones.

Animals↗

PubMed1986

HLA in familial malignant melanoma.

In a family displaying the familial atypical multiple-mole melanoma syndrome, linkage analyses were performed between HLA and an assumed dominant gene respectively determining each of the following affected phenotypes: precursor lesions; cutaneous malignant melanoma (CMM); and precursor lesions or CMM or both. The results suggest that there is a complex mechanism involving several factors, genetic and environmental interacting with the gene determining precursor lesions to cause the neoplastic transformation.

Adolescent↗

PubMed1986

Combined influences of Gm and HLA phenotypes upon multiple sclerosis susceptibility and severity.

In some Caucasian populations, multiple sclerosis (MS) susceptibility has been independently related to given alleles of HLA or Gm systems that respectively code for major histocompatibility complex class I and II antigens or immunoglobulin G heavy chains. Whether given combinations of alleles at both series of loci simultaneously influence MS susceptibility and/or severity was investigated by comparing 147 French MS patients and 226 geographically-matched healthy controls. The G2m(-23)/HLA-B35 phenotype and G1m(-1)/HLA-B7(-)/HLA-DR2 phenotype were respectively associated with significant protection against (relative risk = 0.05) and susceptibility to (relative risk = 4.3) MS. When considering MS severity, the presence of HLA-B7 antigen correlated with a more severe disease in Gm1/Gm3 heterozygous patients, but not in Gm3/Gm3 homozygous patients. Conversely, an HLA-B12-associated milder disease was restricted to Gm3/Gm3 homozygotes. These results demonstrate the combined influence on MS of genetic loci that are unlinked but immune response-associated. Combined Gm and HLA typing is very likely able to serve as a prognostic indicator in this disease.

Disease Susceptibility↗

PubMed1986

[Characterization of lysosomal-type hyaluronidase in the culture medium of 2 cell lines derived from human hepatomas].

A sensitive assay for hyaluronidase was developed using as a substrate, hyaluronic acid insolubilized on polystyrene microtest plates. Hyaluronic acid was measured exploiting the fact that it can bind immune complexes made up with hyaluronectin and alkaline phosphatase-conjugated anti-hyaluronectin antibodies. Hyaluronidase was detected in both cell line culture media. Optimum pH was between 3.25 and 3.75. Sodium chloride dependence was absolute, and the optimum concentration of sodium chloride was between 0.2 and 0.3 M. The activity was not affected by dialysis, and was suppressed by a 5 minute heating at 50 degrees C or by protease treatment. The molecular weight was 68 K as determined by gel permeation chromatography. The results are close to those reported for human lysosomal hyaluronidase.

Carcinoma, Hepatocellular↗

PubMed1985

Modulation of complement receptors of a human monocyte cell line, U-937, during incubation with phorbol myristate acetate: expression of an iC3b-specific receptor (CR3).

The human monocyte line, U-937, derived from an individual with histiocytic lymphoma was studied for the expression of surface C3 receptors, after cultivation in the presence of phorbol myristate acetate (PMA) or T lymphocyte-conditioned medium. Receptors were detected by using EAC4b, EAC3b, EC3b, EAC3bi and EAC3d intermediates. U-937 cells, in exponential growth phase, poorly bound the intermediates; after exposure to PMA or T lymphocyte-conditioned medium, U-937 cells strongly bound both EAC3b and EAC3bi since about 50% of cells rosetted with these intermediates. This binding was totally inhibited by EDTA and by Mac-1 monoclonal antibody, suggesting the presence of only CR3 receptor types on these cells. Although U-937 cells formed rosettes with EAC3b, there was no evidence for the presence of CR1 receptors since no rosette was observed either with EAC4b or with EC3b intermediates (EC3b were prepared by coupling purified C3b to erythrocytes with N-succinimidyl 3-(2-pyridyldithio)propionate. As small amounts of factor H were present on EAC3b intermediates, incubation of EAC3b with U-937 cells induced their transformation into EAC3bi and their binding to CR3. Moreover, U-937 cells did not promote the cleavage of C3b in the presence of factor I alone, suggesting that these cells did not bear a sufficient amount of functionally active CR1. These results demonstrated that U-937 cells predominantly expressed CR3. The study of the kinetics of EAC3bi rosette formation demonstrated that CR3 expression is closely related to PMA activation. We suggest that CR3 activity could result from a phosphorylation of existing receptors.

Antibodies, Monoclonal↗

PubMed1985

IgG (Gm) allotypes and multiple sclerosis in a French population: phenotype distribution and quantitative abnormalities in CSF with respect to sex, disease severity, and presence of intrathecal antibodies.

The association of a given Gm allotype or phenotype with MS susceptibility, as previously described in some Caucasian populations, was not observed in a large French MS group, whether or not considering the possible influence of sex or disease severity. This result could be related to variations in geographical distribution of Gm alleles and MS susceptibility gene(s) or suggests the simultaneous involvement of Gm and other genetic system(s). In contrast, the corresponding CSFs exhibited already known MS-associated abnormalities of IgG1 (G1m) allotype contents, which therefore did not merely result from a Gm-associated MS susceptibility. These quantitative abnormalities were not sex dependent, but may fluctuate with MS severity. The G1m allotype levels in each CSF were not correlated with titers of various intrathecal antibodies but with the number of antibody specificities detected, a picture arguing for a polyclonal, non-antigen-specific activation of G1m allotype-producing B cells present in MS brain.

Antibodies↗

PubMed1985

HLA-DR-dependent variation of intrathecal IgG1 (Gm) allotype synthesis in multiple sclerosis.

Genetic susceptibility to multiple sclerosis (MS) in Caucasians was previously shown to be correlated to the presence of given alleles at the HLA-DR and Gm loci. We now demonstrate that the humoral immune response in MS central nervous system (CNS) is modulated by both loci: the levels of IgG1 subclass and IgG1 allotypes in cerebrospinal fluid of MS patients depend on both their Gm genotype and their HLA-DR2 or HLA-DR7 phenotype. That HLA-DR molecules may either participate in a preferential recruitment of IgG1 allotype-producing B cells in MS CNS or act after such a selective homing is discussed. These results demonstrate that both HLA and Gm loci are synergistically involved in the modulation of the humoral immune response.

Disease Susceptibility↗

PubMed1984

Measurement of serum IgG4 levels by a competitive immunoenzymatic assay with monoclonal antibodies.

A competitive indirect ELISA is described for the measurement of IgG4 levels. It uses a monoclonal anti-subclass and antibody and purified monoclonal IgG4 as standards. This method is sensitive and reproducible and more accurate than hemagglutination inhibition and radial immunodiffusion. Serum IgG4 levels in 173 normal adults were less than 0.01-2.1 mg/ml (mean 0.30 mg/ml) in women and less than 0.01-1.87 mg/ml (mean 0.465 mg/ml) in men.

Adult↗

PubMed1984

A linkage study between HLA and cutaneous malignant melanoma or precursor lesions or both.

In seven pedigrees displaying the familial atypical multiple mole-melanoma (FAMMM) syndrome, three successive linkage analyses were performed between HLA and an assumed dominant gene determining respectively each of the following affected phenotypes: (1) precursor lesions, (2) cutaneous malignant melanoma (CMM), and (3) precursor lesions or CMM or both. Close linkage could be excluded in (1) and (3). However, if the transmission of malignant melanoma itself were assumed to be due to a single gene different from the one responsible for precursor lesions, a maximum lod score of 1.64 was observed at a recombination fraction of 5%, assuming low penetrance values. These different results are discussed in respect to the possible mechanisms causing the familial distribution of these traits. Two alternative hypotheses were proposed. Either the FAMMM syndrome is a rare genetic entity not closely linked to HLA or the association and transmission of precursor lesions and CMM in families are due to several factors among which HLA might play a role.

Disease Susceptibility↗

PubMed1983

Antimelanoma hybridoma antibodies against partially purified melanoma antigen.

We have immunised BALB/c mice with a melanoma antigen obtained after papain solubilisation of the membranes of a metastatic melanoma tumour and fused the immune spleen cells to the mouse myeloma line P3-NS1/1-Ag4.1. The produced hybridoma antibodies (Mel-PV antibodies) recognised the initial melanoma antigen in haemagglutination, but did not react with any of the HLA phenotypes tested by cytotoxicity on a panel of B lymphocytes with known HLA-A and B phenotypes. We rosetted red blood cells coated with protein A with dispersed cells from fresh melanoma tumours, and a high degree of specificity for human malignant melanocytes was observed. Purified Mel-PV antibodies were also tested by indirect immunofluorescence and found to be oriented towards cytoplasmic components of malignant melanoma cells. These results indicate that the use of melanoma antigens for preparing monoclonal antibodies maintained a satisfactory degree of specificity and may be an adequate starting point for defining common and specific antigenic determinants on human melanoma.

Animals↗

PubMed1983

Regulation of the binding of C3-coated particles to human lymphocytes by human complement component H.

Human complement component H was found to modify greatly the binding of C3-coated particles to lymphocytes. We used an experimental model in which lymphocytes were mixed successively with various amounts of H and C3b-coated erythrocytes. At least three mechanisms were postulated to interpret the phenomenon: (i) release of endogenous I by lymphocytes triggered by H through specific binding sites, (ii) cleavage of iC3b by I, promoted by complement receptor type one, and (iii) inhibition of immune adherence by H. Such qualitative and quantitative changes in C3-coated particle recognition by the binding sites might mediate important functions of lymphocytes.

Binding, Competitive↗

PubMed1983

Latent immunoglobulin G (Gm) allotypes: occurrence in the cerebrospinal fluid in some neuropathological states.

Gm allotypes were detected and quantitated by radioimmunoassay (RIA) in paired serum and CSF samples from patients suffering from various neurological diseases. Of 115 patients with neurological disorders (65 MS and 50 others), seven subjects displayed one or two allotypes in their CSF which were absent in serum. The Gm phenotype in the patient's serum allowed us to infer the genotype without the need of familial data. A comparison of the regression curves obtained in RIA from the unexpected allotype in CSF and the counterpart in a normal serum pool argued for an identity of the Gm antigen carried by both inhibitory molecules. The unexpected allotype(s) in CSF can be considered as the product of a latent Gm gene which may be activated by either immune perturbations due to the disease per se or some particular immune regulations in the central nervous system.

Humans↗

PubMed1981

Differential binding of IgG subclasses to enzyme-treated human lymphocytes.

Human erythrocytes coated with each of the four human IgG subclasses were used to detect Fc gamma receptors on human peripheral blood lymphocytes (HPBL). Rosette formation was obtained only with erythrocytes coated with IgG3 (EA gamma 3). Neuraminidase treatment of HPBL induced rosette formation with EA gamma 1, EA gamma 2, and EA gamma 4 complexes. Pronase treatment also induced rosette formation to a lesser extent, but abolished EA gamma 3 rosetting. Trypsin treatment enhanced EA gamma 3 rosette formation. These phenomena occurred on both 'T' and 'non-T' lymphocytes. Erythrocytes coated with small quantities of IgG 3 did not form rosettes with HPBL. Neuraminidase treatment enhanced their binding, whereas pronase did not. These two phenomena occurred only on non-T lymphocytes. Rosette formation with EA gamma 1 was also obtained with lymphocytes stimulated in vitro with mitogens. After 2 days of culture, stimulated lymphocytes expressed receptors that were able to bind both EA gamma 1 and EA gamma 3 complexes. These results suggest the existence of cryptic receptors for IgG1, IgG2, and IgG4 that could be disclosed by neuraminidase and pronase treatment and exposed on stimulated lymphocytes. A hypothesis of one or several Fc gamma receptors is suggested.

Animals↗

PubMed1980

[Augmentation of HL-A A9 antigen in malignant melanoma, principally in metastatic or recurrent forms. Apropos of 105 cases of melanoma of which 34 were serious forms].

HLA-A and B phenotypes of 105 patients suffering from malignant melanomas were determined, with special regard for metastatic form or relapse. A highly significant increase of the HLA-A9 antigen is seen (X2 = 17.47); such data had already been shown by van Wijek [2], but other authors did not find this abnormality when studying melanomas whose histologic form was not specified.

HLA Antigens↗