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T Langon

Publications and source records attributed to T Langon.

4 recordsLinked to original sources

Single cells can sense their position in a morphogen gradient.

Xenopus blastula cells show a morphogen-like response to activin by expressing different genes according to the concentration of activin to which they are exposed. To understand how cells recognize their position in a concentration gradient, it is essential to know whether each cell responds individually to activin concentration. An alternative idea, proposed by previous work, is that cells need to interact with their neighbours to generate a concentration-related response. To distinguish between these ideas, we have cultured blastula cells under conditions which provide different degrees of contact with other cells, allowing nil to maximum communication with their neighbours. The cultures include cells attached to fibronectin and cells resting unattached on an agarose base. The cultures also include cells that have no contact with any cell except their clonal progeny, cells that have lateral contact to neighbouring cells, and cells that are completely enveloped by other cells in a reaggregate. We have used RNase protection and in situ hybridization to assay the expression of the activin-responsive Xenopus genes Xbra, Xgsc, Xeomes, Xapod, Xchordin, Mix1, Xlim1 and Cerberus. We find no difference in gene expression between cells attached to fibronectin and those unattached on agarose. Most importantly, we find that cells respond to activin in a concentration-related way irrespective of their degree of contact with other cells. Therefore interaction among cells is not required for the interpretation of morphogen concentration, at least in the case of the early genes studied here. We conclude that isolated blastula cells can sense and respond individually to activin by expressing genes in a concentration-dependent way.

Activins↗

A novel vector for the study of hepatitis delta virus replication.

In order to study HDV replication without the difficulties caused by the use of a multimeric construction and to obtain a selectable expression vector, a minimal amount of antigenomic HDV cDNA, sufficient to initiate RNA dependent replication was cloned into the plasmid pUTSV1. The first plasmid, pUTdelta1.7, contained 1.7 genomes of HDV cDNA. After transfection of pUTdelta1.7 into HuH7 cells, antigenomic HDV RNA was produced, processed and could enter into the replicative cycle of HDV. However, after transfection of an antigenomic ribozyme mutant (pUTdelta1.7(AGR)) constructed on the same model, plasmid DNA dependent production of genomic HDV RNA was observed, especially in COS7 cells. It seems that a promoter within vector sequences downstream from the HDV insert may initiate counter-clockwise transcription of the plasmid. The presence of two genomic ribozymes in the insert permits the excision of a genome length genomic HDV RNA from this counter-clockwise transcript. In order to allow quantitative analysis of HDV replication, this problem was eliminated by removing the second genomic ribozyme from the insert to give the vector pUTdelta1.5. This vector can be used conveniently for transfection experiments to explore HDV biology.

Animals↗

Therapeutic attempts in infants with nonketotic hyperglycinaemia.

Identical male twins with non-ketotic hyperglycinaemia did not exhibit any development progress while on strychnine treatment. Since other therapeutic attempts with single agents previously had failed in most instances, we tried a combination of various treatment modalities. The results indicated that the administration of glycine receptor antagonist (strychnine) together with a low-protein diet (1.5 gm/kg/day), augmentation of 1-C units (N(5)-formlytetrahydrofolate), and removal of glycine from extracellular fluid (sodium salicylate and sodium benzoate) yielded some clinical improvement and positive biochemical changes in out patients.

Adrenocorticotropic Hormone↗

Analysis of a hepatitis delta virus isolate from the Central African Republic.

Based on the analysis of HDV genomes from different areas of the world, three genotypes of HDV have been identified. Genotype I is the most prevalent and widespread. Genotype II is represented by two isolates from Japan and Taiwan. Genotype III has been found only in the Amazonian basin where it is associated with a history of severe disease, fulminant hepatitis with microvesicular steatosis (spongiocytosis). We report here the cloning and the analysis of the complete viral genome from woodchuck serum-derived HDV RNA after transmission from Central African Republic (RCA) patients with fulminant spongiocytic delta hepatitis. Two overlapping cDNA fragments, covering the entire HDV genome, were generated by RT-PCR and cloned. Three clones obtained from each fragment were fully sequenced. A complete consensus RCA HDV genome was reconstituted. The individual and the consensus nucleotide sequences were compared with those of 16 other fully sequenced isolates belonging to the three genotypes. Phylogenetic trees generated by the neighbour joining method firmly place our isolate in genotype I, and show that this RCA isolate differs significantly from the east African isolates previously analysed. Transfection experiments showed that the isolate is replication-competent, but less so than the control "wild-type" strain. Two novel mutations encountered in this work, one in the antigenomic ribozyme sequence and one affecting delta antigen, were studied.

Amino Acid Sequence↗