Biomedical subjects

S Léonard

Publications and source records attributed to S Léonard.

7 recordsLinked to original sources

PubMed2006

FtcR is a new master regulator of the flagellar system of Brucella melitensis 16M with homologs in Rhizobiaceae.

The flagellar regulon of Brucella melitensis 16M contains 31 genes clustered in three loci on the small chromosome. These genes encode a polar sheathed flagellum that is transiently expressed during vegetative growth and required for persistent infection in a mouse model. By following the expression of three flagellar genes (fliF, flgE, and fliC, corresponding to the MS ring, hook, and filament monomer, respectively), we identified a new regulator gene, ftcR (flagellar two-component regulator). Inactivation of ftcR led to a decrease in flagellar gene expression and to impaired Brucella virulence. FtcR has a two-component response regulator domain as well a DNA binding domain and is encoded in the first flagellar locus of B. melitensis. Both the ftcR sequence and its genomic context are conserved in other related alpha-proteobacteria. During vegetative growth in rich medium, ftcR expression showed a peak during the early exponential phase that paralleled fliF gene expression. VjbR, a quorum-sensing regulator of the LuxR family, was previously found to control fliF and flgE gene expression. Here, we provide some new elements suggesting that the effect of VjbR on these flagellar genes is mediated by FtcR. We found that ftcR expression is partially under the control of VjbR and that the expression in trans of ftcR in a vjbR mutant restored the production of the hook protein (FlgE). Finally, FtcR binds directly to the upstream region of the fliF gene. Therefore, our data support the role of FtcR as a flagellar master regulator in B. melitensis and perhaps in other related alpha-proteobacteria.

Amino Acid Sequence↗

PubMed2006

Variability of the inhibition by total immunoglobulin of in vitro autoantibody-mediated erythrophagocytosis by mouse macrophages.

Several autoimmune diseases, mainly autoantibody-mediated, are attenuated by infusion of total IgG (IVIg). The efficacy varies widely from one patient to another. Using an experimental model of in vitro phagocytosis of autoantibody-coated erythrocytes by mouse macrophages, we analysed the possible causes for such a variability. Our results indicated that the efficacy of the phagocytosis inhibition depends upon different factors, such as the isotype and the extent of polymerization of the immunoglobulin used for the treatment as well as the genetic background of the mice and the state of macrophage activation that can be influenced by concomitant viral infection. The development of an in vitro assay for the phagocytic activity of macrophages might improve the selection of patients susceptible to benefit from IVIg treatment.

Animals↗

PubMed2005

The sheathed flagellum of Brucella melitensis is involved in persistence in a murine model of infection.

Persistence infection is the keystone of the ruminant and human diseases called brucellosis and Malta fever, respectively, and is linked to the intracellular tropism of Brucella spp. While described as non-motile, Brucella spp. have all the genes except the chemotactic system, necessary to assemble a functional flagellum. We undertook to determine whether these genes are expressed and are playing a role in some step of the disease process. We demonstrated that in the early log phase of a growth curve in 2YT nutrient broth, Brucella melitensis expresses genes corresponding to the basal (MS ring) and the distal (hook and filament) parts of the flagellar apparatus. Under these conditions, a polar and sheathed flagellar structure is visible by transmission electron microscopy (TEM). We evaluated the effect of mutations in flagellar genes of B. melitensis encoding various parts of the structure, MS ring, P ring, motor protein, secretion apparatus, hook and filament. None of these mutants gave a discernible phenotype as compared with the wild-type strain in cellular models of infection. In contrast, all these mutants were unable to establish a chronic infection in mice infected via the intraperitoneal route, raising the question of the biological role(s) of this flagellar appendage.

Animals↗

PubMed2002

[Multifocal progressive leukoencephalitis in a patient given fludarabine for chronic lymphoid leukemia].

A 74-year- man was hospitalized for subacute aphasia and right hemiparesis. He had had chronic lymphoid leukemia for 11 years and had been treated 5 months earlier with 3 courses of fludarabine. Magnetic resonance imaging showed lesions of the temporo-occipital white matter compatible with progressive multifocal leukoencephalitis (PML). The presence of JC virus was demonstrated first by in situ hybridation after a brain biopsy and second with polymerase chain reaction on CSF. The diagnosis of PML was confirmed. The causality of fludarabine treatment is discussed.

Aged↗

PubMed2000

Exacerbation of autoantibody-mediated hemolytic anemia by viral infection.

Strong enhancement of the pathogenicity of an antierythrocyte monoclonal antibody was observed after infection of mice with lactate dehydrogenase-elevating virus. While injection of the antierythrocyte antibody alone induced only moderate anemia, concomitant infection with this virus, which is harmless in most normal mice, led to a dramatic drop in the hematocrit and to death of infected animals. In vitro and in vivo analyses showed a dramatic increase in the ability of macrophages from infected mice to phagocytose antibody-coated erythrocytes. These results indicate that viruses can trigger the onset of autoimmune disease by enhancing the pathogenicity of autoantibodies. They may explain how unrelated viruses could be implicated in the etiology of autoantibody-mediated autoimmune diseases.

Anemia, Hemolytic, Autoimmune↗

PubMed2000

Complex formation between potyvirus VPg and translation eukaryotic initiation factor 4E correlates with virus infectivity.

The interaction between the viral protein linked to the genome (VPg) of turnip mosaic potyvirus (TuMV) and the translation eukaryotic initiation factor eIF(iso)4E of Arabidopsis thaliana has previously been reported. eIF(iso)4E binds the cap structure (m(7)GpppN, where N is any nucleotide) of mRNAs and has an important role in the regulation in the initiation of translation. In the present study, it was shown that not only did VPg bind eIF(iso)4E but it also interacted with the eIF4E isomer of A. thaliana as well as with eIF(iso)4E of Triticum aestivum (wheat). The interaction domain on VPg was mapped to a stretch of 35 amino acids, and substitution of an aspartic acid residue found within this region completely abolished the interaction. The cap analogue m(7)GTP, but not GTP, inhibited VPg-eIF(iso)4E complex formation, suggesting that VPg and cellular mRNAs compete for eIF(iso)4E binding. The biological significance of this interaction was investigated. Brassica perviridis plants were infected with a TuMV infectious cDNA (p35Tunos) and p35TuD77N, a mutant which contained the aspartic acid substitution in the VPg domain that abolished the interaction with eIF(iso)4E. After 20 days, plants bombarded with p35Tunos showed viral symptoms, while plants bombarded with p35TuD77N remained symptomless. These results suggest that VPg-eIF(iso)4E interaction is a critical element for virus production.

Amino Acid Sequence↗

PubMed2000

Childhood abuse and platelet tritiated-paroxetine binding in bulimia nervosa: implications of borderline personality disorder.

BACKGROUND: Co-occurrence of bulimia nervosa and borderline personality disorder has been attributed to shared factors, including childhood abuse and disturbances in central serotonin (5-hydroxytryptamine; 5-HT) mechanisms. To explore this notion, we conducted a controlled assessment of childhood abuse and 5-HT function in bulimics with and without borderline personality disorder. METHOD: Forty patients with bulimia nervosa, confirmed with the Eating Disorders Examination interview (14 with borderline personality disorder and 26 without), and 25 normal-eater controls were assessed for clinical symptoms (eating disturbances, mood lability, impulsivity, and dissociation) and childhood sexual and physical abuse. We also conducted tests of platelet tritiated-paroxetine binding in blood samples from 27 of the bulimics (11 with borderline personality disorder and 16 without) and 16 of the controls. RESULTS: Relative to normal eaters, bulimics showed greater affective instability, overall impulsivity, and a history of physical abuse. However, borderline bulimics alone showed elevated motor impulsivity, dissociation, and rates of sexual abuse. Paroxetine-binding tests indicated no differences attributable to comorbid borderline personality disorder, instead linking bulimia nervosa with or without borderline personality disorder to substantially reduced 5-HT transporter density. CONCLUSION: Results suggest relatively autonomous pathologic entities: one, relevant to bulimia nervosa, being associated with abnormal 5-HT transporter function and affective instability, but relatively independent of childhood sexual abuse; another, relevant to borderline personality disorder, onto which sexual abuse, dissociative symptoms, and behavioral impulsivity converge. We propose that abnormal 5-HT function may, however, constitute one basis for the frequent co-occurrence of bulimic and borderline disturbances.

Adolescent↗