Biomedical subjects

C Jacquemot

Publications and source records attributed to C Jacquemot.

9 recordsLinked to original sources

PubMed2001

Interleukin-7 and infection itself by human immunodeficiency virus 1 favor virus persistence in mature CD4(+)CD8(-)CD3(+) thymocytes through sustained induction of Bcl-2.

The sequence of events and the mechanisms leading to the destruction of the thymus during human immunodeficiency virus (HIV) infection are still poorly characterized. Investigated here are the survival capacity on HIV-1 infection of the mature single-positive CD4(+)CD8(-)CD3(+) (SP CD4(+)) and the intermediate CD4(+) CD8(-)CD3(-) thymocytes previously shown to be able to replicate the virus in the thymic microenvironment. It is demonstrated that the mature SP CD4(+) thymocytes exhibit a high survival capacity despite the production of a high yield of viruses. Interleukin-7, reported to be a crucial cofactor of tumor necrosis factor (TNF) to promote HIV replication, is shown here to counteract the apoptotic activity of TNF. Resistance to apoptosis of SP CD4(+) cells is conferred by a high expression of the IL-7 receptor (IL-7R) associated with the capacity of IL-7 to permanently up-regulate Bcl-2. In addition, this high Bcl-2 level is further enhanced by infection itself. In contrast, intermediate thymocytes, which replicate the virus at a lower level, are more sensitive to apoptosis, and their differentiation into double-positive CD4(+)CD8(+)CD3(-) (DP CD3(-)) cells strongly increases their death rate on infection. This sensitivity is related to a lower expression of IL-7R and Bcl-2 in intermediate thymocytes, which further decreases at the DP CD3(-) stage. In addition, a decreased level of Bcl-2 is observed in this subset during infection. Altogether these data suggest that in vivo, HIV infection might create a persistent virus reservoir within the SP CD4(+) thymocytes, whereas the later infection of intermediate cells might lead to thymopoiesis failure.

Antigens, Differentiation, T-Lymphocyte↗

PubMed1994

[Prenatal diagnosis of osteogenesis imperfecta].

The authors report a prenatal diagnosis of osteogenesis imperfecta or Porak and Durante disease, in which the child survived. The diagnosis was made by ultrasonography which revealed major abnormalities of osteogenesis more particularly affecting the lower limbs, which were short and deformed. Other essential features of this syndrome are osteoporosis, hyperrelaxation of ligaments and blue sclerae. This rare and genetic condition is due to type I collagen abnormalities. It is often governed by dominant transmission but manifestation of the gene is variable within a given family. Molecular biology and genetic studies offer new possibilities of prenatal diagnosis, but ultrasonography remains the investigation of choice, possibly helped by X-ray of the uterine contents.

Adult↗

PubMed1991

Exposed epitopes on a Trypanosoma equiperdum variant surface glycoprotein altered by point mutations.

African trypanosomes are covered by a dense protein layer that is immunologically distinct on different trypanosome isolates and is termed the variant surface glycoprotein (VSG). The different VSGs are expressed in a general order, where some VSGs appear preferentially early in infection and others only later. The exposed epitopes on a late antigen, VSG 78, of T.equiperdum were studied by the technique of monoclonal antibody (MAb) escape selection. MAbs that neutralize trypanosomes bearing VSG 78 reacted with the VSG only when it was attached to the trypanosome surface, suggesting that the most immunogenic surface epitopes are conformational. Trypanosome clones resistant to one of the MAbs yet still expressing VSG 78 or 78(20) were isolated in vitro. Two independent variants resistant to MAb H3 changed Ser192 to Arg by a single base change in the VSG gene and a variant resistant to MAb H21 had a single base change that converted Gln172 to Glu. A variant resistant to MAb H7 had several changes in the VSG gene, a gene conversion in the 5' region and an isolated mutation in codon 220 that is proposed to be responsible for the resistance phenotype. The isotypic bias of the MAbs against VSG 78 and an analysis of the natural variants that are resistant to MAb 78H21 suggest that glycosylation plays a role in the immunogenicity of these proteins. The analysis defines some of the exposed amino acid residues and demonstrates that VSG genes are altered by mutations and small gene conversions as well as replaced by large gene conversion-like events. The results provide biological data supporting the model of VSG structure obtained by crystallographic studies.

Amino Acid Sequence↗

PubMed1991

A study of the genomic diversity of Plasmodium falciparum in Senegal. 1. Typing by Southern blot analysis.

The genomic polymorphism of Plasmodium falciparum was investigated in a series of samples collected in Senegal during one transmission season. Restriction site polymorphism was studied by Southern blot analysis using six different probes. The patterns of the ribosomal RNA genes and of the gene coding for antigen 2L indicated a limited genomic polymorphism. Sequences hybridizing to the repeats of the Palo Alto/Wellcome serotype of S-antigen were found in one out of twelve isolates examined. This strain was shown to express the Palo Alto serotype. Restriction fragment length polymorphism was observed for the 332 gene and the 11.1 locus. The hybridization patterns showed that each sample had a distinct 11.1 locus. A comparison of three probes (332, 11.1 and rep20) detecting fragment length polymorphism indicated that maximum sensitivity was obtained using the subtelomeric repeats rep20; less sensitive patterns were observed using the 11.1 27 bp repeat probe. By using these three probes it was found that all samples were genetically distinct.

Animals↗

PubMed1991

A study of the genomic diversity of Plasmodium falciparum in Senegal. 2. Typing by the use of the polymerase chain reaction.

The genomic polymorphism of Plasmodium falciparum was investigated in a series of samples collected in Senegal during one transmission season. PCR analysis was performed on several genes coding for blood-stage antigens: the gene for the major merozoite surface antigen P190, the gene for the second merozoite surface antigen MSA2 and the gene coding for antigen 96tR/GBP130. In each case, several distinct forms of the genes studied were observed. Both the MAD20 and K1 allelic families of P190 genes were observed. PCR analysis of a single variable region did not differentiate each isolate. However, when the data obtained for several markers are combined, each isolate had a specific genotype. Thus, using PCR to study in parallel several loci is a useful tool to genetically type strains.

Alleles↗

PubMed1988

The genomic organization and transcription of the ubiquitin genes of Trypanosoma cruzi.

We describe here the organization of the ubiquitin genes of the parasitic protozoan Trypanosoma cruzi. T. cruzi contains greater than 100 ubiquitin coding sequences all of which are clustered into a 27 kb segment of the genome. Two types of ubiquitin coding sequences were found. There are five fusion genes (FUS1-5) consisting of a ubiquitin coding sequence fused to a basic non-ubiquitin sequence. The T. cruzi ubiquitin fusion protein is 84% homologous to the product of the UBI gene of Saccharomyces cerevisiae. The non-ubiquitin domains of the two proteins are 67% homologous. There are five polyubiquitin coding genes (PUB) each consisting of varying lengths of polyubiquitin coding sequence and terminating with a single copy of the larger fusion gene. Transcription of the ubiquitin genes results in the generation of six major poly(A)+ mRNAs. The pattern of transcription accurately reflects the genomic organization, in that the transcripts consist of either a single copy of the ubiquitin fusion coding sequence or varying lengths of polyubiquitin (up to 52 copies of the ubiquitin coding unit) each ending with a single copy of the ubiquitin fusion sequence. Finally, there are heat shock elements 5' to the PUB genes and transcription patterns are altered under conditions of stress.

Amino Acid Sequence↗

PubMed1984

Re-expression of an inactivated variable surface glycoprotein gene in Trypanosoma equiperdum.

Variable surface glycoprotein (VSG) genes in African trypanosomes are often activated by the duplicative transposition of a silent basic copy (BC) gene into an unlinked telomerically located expression site, producing an active expression-linked copy (ELC) of that gene. However, some BC genes that are already linked to a telomere are activated without apparent duplication or transposition. We have recently shown that an active VSG ELC can be inactivated in situ, apparently without rearrangement. To explain these observations it has been suggested that VSG genes that are associated with chromosome telomeres are activated by chromosome end exchanges that occur at a considerable distance upstream from the genes themselves and place them cis to a unique VSG expression element. In an attempt to test this model we derived five VSG-1 expressing variants from BoTat-2, a VSG-2 expressing variant of Trypanosoma equiperdum which carries an inactive residual VSG-1 ELC (R-ELC) as well as the active VSG-2 ELC near unlinked chromosome telomeres. We examined the fates of the VSG-2 ELC and the VSG-1 R-ELC in these variants. All five had maintained the VSG-1 R-ELC; three in a reactivated form and two in an inactive state. The latter two variants carried new, active VSG-1 ELCs: one in the site that had previously contained the VSG-2 ELC and one in a previously unidentified site. The VSG-2 ELC was lost in all five of the variants. The results are not consistent with the simple chromosome end exchange model, which predicts that the VSG-2 ELC would be inactivated but not deleted when the VSG-1 R-ELC was reactivated.

Animals↗

PubMedDate not supplied

Antigenic variation in Trypanosoma equiperdum.

Trypanosoma equiperdum is an African trypanosome that causes dourine in horses. Like the other African trypanosomes, T. equiperdum escapes elimination by the immune system of its host by using an elaborate system of antigenic variant. The trypanosomes are covered by a coat consisting of a single protein called the variable surface glycoprotein (VSG) that acts as the major trypanosome immunogen. As the host responds to one VSG, trypanosomes covered with another VSG become dominant. There is a loose order of appearance of these VSG during the infection. The factors that affect the timing of VSG expression and the effective size of the VSG repertoire in T. equiperdum are reviewed. The VSG genes are generally activated by a process of duplicative transposition involving the duplication of a silent VSG gene and inserting a copy of the gene into an expression site. The order of VSG expression is related to the amount of homology between the silent gene and the expression site. The genes expressed late in infection lack extensive homology with the expression site and depend on homology with the gene in the expression site. The genes coding for VSG expressed late in infection are hybrid genes because of this mode of transfer. This transfer mechanism allows the trypanosome to create complex VSG genes from parts of several different silent genes that are each pseudogenes. Additionally, data are presented showing that only a limited portion of the VSG is actually seen by the host immune system. These factors indicate that the effective VSG repertoire is greater than the number of VSG genes in the trypanosome genome.

Animals↗

PubMedDate not supplied

[Assay of human anti-exoproteins to group A streptococci by microhaemagglutination: correlation with anti-streptolysin O and various anti-enzymes (author's transl)].

A microhaemagglutination test in disposable U plates has been devised for rapid, quantitative evaluation in antistreptococcal antibodies in human sera. Fresh or freeze-dried glutaraldehyde-treated sheep erythrocytes sensitized with over fifteen extracellular proteins released by group A Streptococcus pyogenes including streptolysin O, deoxyribonucleases, hyaluronatelyase, streptokinase and nicotinamide dinucleotide glycohydrolase were used. Haemagglutination and anti-streptolysin O (ASLO) titers were determined in parallel on 434 serum specimens from 123 healthy subjects ("controls") and 311 patients with a history of supposed or evident streptococcal infection. The titration of the four above-mentioned anti-enzyme antibodies has also been made on about 100 sera from both groups. Haemagglutination titre (HT) was less than 800 in control sera. By contrast it was greater than 800 up to 12 800 in patients specimens. Very good correlation was found between HT on the one hand and ASLO or anti-SK, anti-HA and anti-NADase antibodies on the other hand. HT and anti-DNase B antibodies were less correlated. Haemagglutination titres appear to rise earlier than serological titres of conventional streptococcal antibodies. The haemagglutination test described may be particularly helpful as a rapid serologic indicator of streptococcal infections and more reliable than the titration of ASLO alone, or of any one of anti-enzyme antibodies.

Antibodies, Bacterial↗