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Biomedical subjects

C Devaux

Publications and source records attributed to C Devaux.

At least 73 records · Page 4Linked to original sources
PubMed1997

Transrepression of lck gene expression by human T-cell leukemia virus type 1-encoded p40tax.

To understand the mechanism of p56lck protein downregulation observed in human T cells infected by human T-cell leukemia virus type 1 (HTLV-1), we have investigated the ability of the 3' end of the HTLV-1 genome as well as that of the tax and rex genes to modulate p56lck protein expression and p56lck mRNA synthesis. By using Jurkat T cells stably transfected with constructs that expressed either the 3' end of the HTLV-1 genome (JK C11-pMTEX), the tax gene (JK52-Tax) or the rex gene (JK9-Rex), we found that the expression of p40tax (Tax) was sufficient to modulate p56lck protein expression. Similarly, we found that the expression of the mRNA which encoded p56lck was repressed in Jurkat T cells which expressed Tax. This downregulation was shown to be proportional to the amount of tax mRNA found in the transfected cells, as evidenced by experiments that used cells (JPX-9) stably transfected with a tax gene driven by a cadmium-inducible promoter. Furthermore, cadmium induction of Tax in JPX-9 cells transiently transfected with a construct containing the chloramphenicol acetyltransferase (CAT) gene under control of the lck distal promoter (lck DP-CAT) resulted in the downregulation of CAT gene expression. In contrast, cadmium induction of Tax in JPX-9 cells transiently transfected with a CAT construct driven by a lck DP with a deletion extending from position -259 to -253 (a sequence corresponding to a putative E-Box) did not modulate CAT gene expression, suggesting that the effect of Tax on p56lck is mediated through an E-Box binding protein.

Cell Line↗
PubMed1996

A conserved sequence region of scorpion toxins rendered immunogenic induces broadly cross-reactive, neutralizing antibodies.

Scorpion toxins constitute a family of proteins with a high degree of sequence diversity but a common mode of action. Neutralization of the toxic effects of scorpion stings by serotherapy is limited due to the various serotypes expressed by these proteins. We explored the possibility of raising antibodies to conserved parts of the toxins which could recognize several members of the family. We established the variability profile of a set of 25 scorpion toxin sequences, then evaluated systematically by peptide-scanning methods the antigenicity of one scorpion toxin. The most conserved regions were generally very poorly antigenic. One exception was the N-terminal region, which is both conserved and antigenic. Antibodies were raised in rabbits against an eight-residue synthetic peptide mimicking the N-terminal region. These peptide antibodies were cross-reactive with several scorpion toxins belonging to different serotypes and neutralized both the pharmacological effects (binding to rat brain synaptosomes) and the biological activity (toxicity in mice) of the parent toxin. The molecular model of the toxin indicates that antibody binding to residues 1-8 probably either masks some residue(s) of the N-terminus critical for the biological activity or overlaps with the epitope previously defined by neutralizing monoclonal antibody. These findings could open the way for new therapeutic strategies for the medical care of envenomations.

Amino Acid Sequence↗
PubMed1996

Binding of HIV-1 virions or gp120-anti-gp120 immune complexes to HIV-1-infected quiescent peripheral blood mononuclear cells reveals latent infection.

HIV-1-infected quiescent CD4+ cells harbor the virus in an inactive state until subsequent activation. The possibility that HIV-1 itself and the virus envelope glycoprotein 120 (gp120) might be important agents of this activation was investigated. The present data indicate that binding of heat-inactivated HIV-1 (iHIV-1) to infected resting PBMCs was sufficient to activate NF-kappa B and AP-1, to induce transition from the G0/G1 stage of the cell cycle to the S/G2/M stage, to induce cell surface expression of CD25, to stimulate provirus integration, and to commit cells to produce virus. The cumulative amount of HIV-1 produced by iHIV-1-stimulated cells strictly depended on the concentration of p24gag in the virion preparations used for stimulation. Moreover, virus production was not evidenced in infected resting cells exposed to iHIV-1 previously incubated with soluble CD4 (sCD4), indicating that activation requires a contact between HIV-1 envelope glycoproteins and cell surface CD4. Although soluble gp120 did not stimulate virus production, we found that transition to the S/G2/M stage of the cell cycle, cell surface expression of activation Ags, and virus production were stimulated by cross-linking of CD4 by gp120-anti-gp120 immune complexes. Finally, incubation of gp120-anti-gp120 immune complexes with sCD4 inhibited these effects. These findings suggest that virions and gp120 anti-gp120 immune complexes found in infected patients at all times of infection can stimulate virus production in CD4+ cells harboring HIV-1 in an inducible state.

Antigen-Antibody Complex↗
PubMed1996

An antibody that binds domain 1 of CD4 inhibits replication of HIV-1, but not HTLV-I, in a CD4-positive/p56lck-negative HTLV-I-transformed cell line.

mAbs that bind to the Ig CDR3-like region in D1 domain of the CD4 molecule can inhibit the HIV-1 life cycle in CD4-positive T cells and lymphoblastoid cell lines at the stage of transcription. This antiviral effect requires the integrity of the cytoplasmic tail of CD4, which acts as a signal transduction region through its association with protein tyrosine kinases such as p56Ick. Here we investigated the role of p56Ick in the cascade of molecular events that control HIV-1 transcription in cells treated with anti-CD4 mAb directed against the Ig CDR3-like region. The Ig CDR3-like region-specific mAb, 13B8-2, blocked HIV-1 production in CD4-positive/p56Ick-negative HTLV-I-producing MT2 cells superinfected by HIV-1Lai, but had no effect on HTLV-I production, although it did inhibit Tax-induced NF-kappa B translocation. These results raise the possibility that an as yet unidentified tyrosine kinase may be capable of associating with CD4 and mediating intracellular signaling.

Antibodies, Monoclonal↗
PubMed1996

HIV induces activation of phosphatidylinositol 4-kinase and mitogen-activated protein kinase by interacting with T cell CD4 surface molecules.

T cell surface CD4 molecules act as co-receptors that amplify the T cell receptor (TcR)/CD3-induced signal transduction by a mechanism that requires the interaction of CD4 with p56lck tyrosine kinase (Veillette et al.; Nature 1989 338:257). Here, we demonstrate that in the absence of TcR signaling, heat-inactivated HIV-1 (HIV-HI) also elicits a cascade of events generally considered to convey a positive signal, such as protein tyrosine phosphorylation, phosphatidylinositol 4-kinase and mitogen-activated protein kinase activation. These results contribute to understand better the control that HIV may exert on its own replication or on T cell apoptosis by modulating the activation status of its target cells through its interaction with T cell surface CD4 molecules.

1-Phosphatidylinositol 4-Kinase↗
PubMed1996

What role does dietary protein restriction play in the management of chronic renal failure in dogs?

Dietary protein restriction has been the mainstay of conservative medical management of canine renal failure for many years. Although dietary protein restriction minimizes many signs of uremia, its potential benefits to the progression of renal failure are now being questioned. Two case scenarios of different degrees of renal failure are described; guidelines for dietary protein restriction are based on currently available scientific knowledge.

Animals↗
PubMed1996

Adverse events in patients treated with 5-aminosalicyclic acid: 1993-1994 pharmacovigilance report for Pentasa in France.

BACKGROUND: The incidence of the side-effects of 5-aminosalicylic acid (5-ASA) in clinical practice is not known. AIM: To present the safety reports on the use of Pentasa in France. METHODS: Pentasa-related adverse events were recorded from 1 January 1993 to 31 December 1994. Spontaneous reports to Ferring S.A. came from physicians or pharmacovigilance regional centres. RESULTS: In 1993 and 1994, 51 and 79 adverse events were reported; the estimated gross incidence was 6.6 and 9.0 per million days of therapy. Detailed information was obtained 64% of cases in 1993 and 53% in 1994. Adverse events with a high likelihood of causalty included five cases of diarrhoea, 14 cases of pancreatitis, seven cases of liver abnormalities, seven of blood dyscrasias, two cases of renal insufficiency (one of which was in a fetus), and eight of cardiac disorders including three myocarditis. CONCLUSIONS: Pentasa seldom has adverse effects. The majority of the adverse events do not seem to be dose-related. Clinicians should be aware of exceptional but severe adverse events including pancreatitis, cardiac disorders, blood dyscrasias and renal insufficiency.

Aminosalicylic Acids↗
PubMed1996

Inhibition of human immunodeficiency virus type 1 production in infected peripheral blood mononuclear cells by human leukocyte antigen class I-specific antibodies: evidence for a novel antiviral mechanism.

A well-characterized mechanism by which anti-HLA class I monoclonal antibodies (MAb) inhibit human immunodeficiency virus type 1 (HIV-1) propagation in in vitro cell cultures is the neutralization of the virus through interactions with HLA molecules associated with the virion envelope. Yet, the possibility that another mechanism of inhibition might affect a postbinding stage of the virus life cycle has been strongly suggested by our previous investigations. To demonstrate that the interaction of MAb B1-1G6 with the light chain of cell surface-expressed HLA class I molecules inhibits a postbinding step of the HIV-1 life cycle, peripheral blood mononuclear cells (PBMCs) were exposed to viruses grown in HLA class I-negative, CD4-positive cells (these viruses, which did not carry HLA class I molecules, cannot be neutralized by anti-HLA MAb during the first round of infection), and PCR was used at various times postexposure to search for the different forms of HIV-1 DNA and RNA in virus-exposed PBMCs cultured in either the presence or [correction of] absence of MAb B1-1G6. Although viral DNA was found in MAb B1-1G6-treated cells, spliced HIV-1 mRNA could not be detected in those cells. In contrast, HIV-1 gene expression was found in HIV-1-infected PBMCs treated with B9-12-1, another HLA class I-specific MAb which prevents infection of cells by cell-free viruses but which fails to inhibit cell-to-cell transmission of HIV-1. These results highlight a second antiviral mechanism by which anti-HLA MAb inhibit in vitro HIV-1 propagation.

Antibodies↗
PubMed1995

Recombinant and chemical derivatives of apamin. Implication of post-transcriptional C-terminal amidation of apamin in biological activity.

The use of the colicin A lysis protein to direct the extracellular release of a fusion protein from Escherichia coli was investigated as an approach for the preparation of recombinant animal toxins. Apamin, a bee venom neurotoxin, was used as the model toxin. It is reticulated by two disulfide bridges and interacts with small conductance Ca(2+)-activated K+ channels. Substantial amounts of free recombinant apamin were obtained by CNBr cleavage of the fusion protein [col-(1-171)-apa] and HPLC purification. It was recognized by conformation-dependent monoclonal antibodies with a K0.5 value close to that for natural apamin, indicating that folding was correct. In toxicity and binding experiments, the recombinant apamin displayed low activity. The recombinant and natural molecules differed by the amidation of the C-terminal histidine residue. Previous structure/activity relationship studies do not implicate this C-terminal residue in activity but the role of its amidation was not investigated. An apamin analog with a non-amidated C-terminal residue was then chemically synthesized. The biological properties of both recombinant and chemical molecules were determined. Amidation of the C-terminal alpha-carboxyl of apamin appears to be essential for full expression of its biological activity.

Amides↗
PubMed1995

Use of dantrolene in experimental scorpion envenomation by Androctonus australis hector.

Hyperthermia and profuse perspiration are rarely absent in severe cases of scorpion envenomation. Based on these observations, the aim of this study was to determine the therapeutic effects of dantrolene, on experimental poisoning by the venom of Androctonus australis hector. Dantrolene is a directly acting muscle relaxant which lowers the body temperature in malignant hyperthermia. The results indicate that the early use of this drug raises the LD50 in experimentally poisoned mice. If these results are transposable to humans, dantrolene could be a useful therapeutic adjuvant.

Animals↗
PubMed1995

Beta-endorphin in multiple trauma victims.

BACKGROUND: In animals and in humans, stress is known to be accompanied by increased beta-endorphin secretion. METHODS: Blood samples from 47 patients in a state of stress induced by multiple trauma were assessed for beta-endorphin concentration by radioimmunoassays. RESULTS: We show that there is a clearcut correlation (Spearman's R = 0.72, P = 2.1 x 10(-6) between the level of consciousness evaluated with the Glasgow score and levels of circulating beta-endorphin. In addition, beta-endorphin levels are higher than normal in patients with Glasgow coma with scores higher than seven, and lower than normal in those with Glasgow coma scores of seven or less. Finally, in the complete absence of stress (shown by the lack of brain activity in six irreversible coma patients), there is a severe drop in the level of circulating beta-endorphin. CONCLUSION: beta-endorphin serum levels correlate with the state of consciousness of multiple trauma patients.

Adult↗
PubMed1995

beta-Endorphin and blood pressure in multiple trauma victims.

In addition to pain and stress, endogenous opiates and in particular beta-endorphin could be involved in the modulation of cardiovascular parameters. Several studies have thus shown increases in plasma beta-endorphin levels in the course of septic or hypovolemic shock. Our study involving 44 multiple trauma patients indicates that even in the absence of any hemodynamic disorders, there is a correlation between systolic blood pressure and plasma beta-endorphins. These results argue in favor of the existence of feedback between systolic blood pressure and plasma beta-endorphins.

Adult↗
PubMed1995

Antigenic analysis of HIV type 1 external envelope (Env) glycoprotein C2 region: implication for the structure of Env.

To determine whether the amino acid sequence extending from residue 273 to residue 288 in the second conserved region C2 of the HIV-1 envelope glycoprotein represents a target for antibodies on monomeric and oligomerized HIV-1 gp120env, we characterized several antisera and monoclonal antibodies (MAb) raised against C2 synthetic peptides. A cross-reactive epitope was evidenced on HIV-1Lai and HIV-1Eli C2-derived peptides, but was not encountered on HIV-2 C2-derived peptide. This epitope was found to be expressed on the native monomeric gp120env but was not detected in the context of oligomeric Env, suggesting this region is sequestered in the oligomeric molecule. Preincubation of oligomeric Env with sCD4 apparently failed to expose this epitope. Our results suggest that the amino acid sequence extending from residue 273 to residue 288 in C2 of HIV-1 gp120env may be involved in intermolecular interaction within the oligomeric Env complex.

Amino Acid Sequence↗
PubMed1995

Functional epitope analysis of the human CD4 molecule: antibodies that inhibit human immunodeficiency virus type 1 gene expression bind to the immunoglobulin CDR3-like region of CD4.

We recently demonstrated that monoclonal antibody (MAb) 13B8-2, specific for the immunoglobulin (Ig) complementary determining region 3 (CDR3)-like region of the CD4 molecule, inhibits viral transcription in human immunodeficiency virus (HIV)-infected CEM cells and HIV type 1 (HIV-1) promoter activity. Here, we have studied the capacity of several MAb specific for the D1 domain of CD4, including anti-CDR2-like (Leu-3a and ST4) and anti-CDR3-like (13B8-2 and ST40) MAb, and for the D2 domain of CD4 (BL4) to inhibit both provirus transcription in HIV-1LAI-infected CEM cells and transcription of the chloramphenicol acetyltransferase (CAT) gene under control of the HIV-1 long terminal repeat in transiently transfected CEM cells. We found that HIV-1 promoter activity and provirus transcription are inhibited only by MAb that bind to the CDR3-like region in domain 1 of CD4. Moreover, we demonstrated that the Fab fragment of an anti-CDR3-like region-specific anti-CD4 MAb is a powerful inhibitor of HIV-1 promoter activity. These results have implications for understanding the role of the CDR3-like region in CD4 T-cell signaling, which controls provirus transcription.

Antibodies, Monoclonal↗
PubMed1995

The cytoplasmic tail of CD4 is required for inhibition of human immunodeficiency virus type 1 replication by antibodies that bind to the immunoglobulin CDR3-like region in domain 1 of CD4.

Monoclonal antibodies (MAb) directed against the immunoglobulin complementary determining region 3 (CDR3)-like region of the CD4 molecule inhibit human immunodeficiency virus type 1 (HIV-1) transcription. We report here data showing that the cytoplasmic tail of CD4 is required for such inhibition to be achieved. To this aim, we studied the effect of MAb 13B8-2 treatment on (i) HIV-1 production in A2.01 cells, which express different forms of the CD4 gene, (ii) Tat-induced HIV-1 promoter activation, and (iii) mitogen-activated protein kinase (MAPK) activation, which is induced in CD4-positive cells by HIV-1 cross-linking of CD4. Inhibition of HIV production by 13B8-2 MAb treatment was consistently observed in cells expressing wild-type CD4 and cells expressing a hybrid CD4-CD8 molecule (amino acids 1 to 177 of CD4 fused to the hinge, transmembrane, and cytoplasmic domains of CD8). However, no delay in HIV-1 production was observed in cells expressing a truncated CD4 which lacks the cytoplasmic domain (CD4.401). Chloramphenicol acetyltransferase assays demonstrated that Tat-dependent activation of the HIV-1 long terminal repeat promoter was inhibited by MAb 13B8-2 in A2.01/CD4 and A2.01/CD4-CD8 but not in A2.01/CD4.401 cells. Finally, we found that MAb 13B8-2 treatment inhibited the activation of MAPK induced in A2.01/CD4 and A2.01/CD4-CD8 following cross-linking of CD4 by HIV-1.

Antibodies, Monoclonal↗
PubMed1994

The cytoplasmic domain of CD4 plays a critical role during the early stages of HIV infection in T-cells.

The role played by the cytoplasmic domain of the CD4 molecule in the process of HIV infection was investigated, using A2.01 cells which express different forms of the CD4 gene. A delay in HIV production was consistently observed in cells expressing a truncated CD4 which lacks the cytoplasmic domain (CD4.401) compared with cells expressing the wild type CD4. The delay was much less in cells expressing a hybrid CD4-CD8 molecule (amino acids 1-177 of CD4 fused to the hinge, transmembrane and cytoplasmic domains of CD8). Yet the extent of viral entry and reverse transcription, monitored by semi-quantitative PCR, was similar in each cell type studied. For further study of the mechanism responsible for delayed HIV replication in the A2.01/CD4.401 cell line, cells were treated with phytohaemagglutinin (PHA), 24 h after HIV infection. Under such experimental conditions HIV production was detected at the same time in the culture supernatants of A2.01/CD4 and A2.01/CD4.401 cells. Moreover, we found that CD4 oligomerization by HIV-1 induced NF-kappa B translocation in A2.01/CD4 and A2.01/CD4-CD8 but not in A2.01/CD4.401 cells. This was consistent with CAT assay experiments which provided evidence for Tat-independent NF-kappa B mediated activation of HIV-1 LTR promoter after HIV binding to CD4 in A2.01/CD4 and A2.01/CD4-CD8 but not in A2.01/CD4.401 cells. In contrast to results published recently by Tremblay et al. (1994, EMBO J., 13, 774-783), we propose that a positive cellular signal initiated following oligomerization of the CD4 by the virus itself is involved in NF-kappa B-dependent early HIV transcription in A2.01/CD4 cells.

Base Sequence↗
PubMed1994

Jacalin, a lectin with anti-HIV-1 properties, and HIV-1 gp120 envelope protein interact with distinct regions of the CD4 molecule.

Jacalin is a multimeric plant lectin able to interact with the lymphocyte cell-surface molecule CD4, a known receptor for the human immunodeficiency virus type 1 (HIV-1). Moreover, jacalin is able to block HIV-1 infection of CD4+ lymphoblastoid cells. Here we studied whether jacalin prevents HIV-1 gp120-CD4 interactions. We found (i) that jacalin did not inhibit HIV-1 Lai-induced syncytium formation that requires gp120-CD4 interactions; (ii) that jacalin prevented neither rgp120 binding to cell-surface CD4 nor sCD4 binding to viral envelope proteins expressed at the surface of HIV-1-infected lymphoblastoid cells; (iii) that jacalin did not compete for binding to CD4 with anti-CD4 mAb specific for the CDR2- or CDR3-like regions of the D1 domain of CD4; (iv) that jacalin did not bind a recombinant soluble molecule containing the D1/D2 domains of CD4; and, (iv) that jacalin binding to CD4 is inhibited by sugars known to interact with the lectinic-site of jacalin. These data have implications for the understanding of the mechanism by which jacalin blocks HIV-1 infection of CD4+ cells.

Acetylgalactosamine↗