Pseudo-aneurysm of the popliteal artery following an arthroscopic meniscectomy: report of a pediatric case.
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Anastomosis, Surgical↗
Biomedical subjects
C Gautier
Publications and source records attributed to C Gautier.
The compositional properties of human genes.
The present work represents the first attempt to study in greater detail previously proposed compositional correlations in genomes, based on a body of additional data relating to gene localizations as well as to extended flanking sequences extracted from gene banks. We have investigated the correlations that exist between (1) the GC levels of exons of human genes, and (2) the GC levels of either intergenic sequences or introns associated with the genes under consideration. In both cases, linear relationships with slopes close to unity were found. The similarity of the linear relationships indicates similar GC levels in intergenic sequences and introns located in the same isochores. Moreover, both intergenic sequences and introns showed GC levels 5-10% lower than the corresponding exons. The above findings considerably strengthen the previously drawn conclusion that coding and noncoding sequences (both inter- and intragenic) from the same isochores of the human genome are compositionally correlated. In addition, we find linear correlations between the GC levels of codon positions and of the intergenic sequences or introns associated with the corresponding genes, as well as among the GC levels of codon positions of genes.
Base Composition↗
Correlations between the compositional properties of human genes, codon usage, and amino acid composition of proteins.
We have analyzed the correlation that exists between the GC levels of third and first or second codon position for about 1400 human coding sequences. The linear relationship that was found indicates that the large differences in GC level of third codon positions of human genes are paralleled by smaller differences in GC levels of first and second codon positions. Whereas third codon position differences correspond to very large differences in codon usage within the human genome, the first and second codon position differences correspond to smaller, yet very remarkable, differences in the amino acid composition of encoded proteins. Because GC levels of codon positions are linearly correlated with the GC levels of the isochores harboring the corresponding genes, both codon usage and amino acid composition are different for proteins encoded by genes located in isochores of different GC levels. Furthermore, we have also shown that a linear relationship with a unit slope and a correlation coefficient of 0.77 exists between GC levels of introns and exons from the 238 human genes currently available for this analysis. Introns are, however, about 5% lower in GC, on average, than exons from the same genes.
Amino Acid Sequence↗
Vaccinia recombinants expressing secreted and transmembrane forms of breast cancer-associated epithelial tumour antigen (ETA).
Monoclonal antibody H23 identifies a polymorphic epithelial tumour antigen (ETA) that is aberrantly expressed in breast cancer and which may afford a target for active immunotherapy. We recently reported the cloning of H23-ETA genomic and cDNA clones. H23-ETA contains a multiple internal tandem repetition of a 20 amino acid motif and sequence analysis predicted two mRNA species encoding different ETA proteins, one harbouring a C-terminal potentially transmembrane hydrophobic zone (T) and a second form (S) that lacks this zone. We report that both RNA species can be detected in breast cancer cells. To further characterize the encoded proteins we have constructed vaccinia virus recombinants, VV-ETA-S and VV-ETA-T, separately expressing the alternative forms. Despite selective loss of internal tandem repeat elements during propagation of recombinant vaccinia, the encoded polypeptides were efficiently recognized by H23 monoclonal antibody. Immunoprecipitation revealed that ETA encoded by the S recombinant was secreted into the culture medium whereas the T form remained tethered at the cell surface. Both forms were readily detected in infected cells by immunofluorescence. Abnormal mobility of the T polypeptide indicated post-translational cleavage that may permit the extracellular domain of the T-polypeptide to be shed from the cell surface. Further, fluorescence-activated cell sorting analysis shows that the S form of the polypeptide is also partly present at the cell surface. Vaccinia recombinants expressing ETA may be of utility in the active immunotherapy of breast cancer.
Antigens, Neoplasm↗
The distribution of genes in the human genome.
Previous investigations on the human genome determined: (i) the base compositions (GC levels) and the relative amounts of its isochore families; (ii) the compositional correlations (i.e., the correlations between GC levels) between third codon positions of a set of genes and the DNA fractions in which the genes were localized; and (iii) the compositional correlations between (a) third and first + second codon positions, as well as that between (b) introns and exons from the set of 'localized genes' and from all the coding sequences and genes (genomic sequences of exons + introns) available in gene banks. Here, we have shown that the correlations (iii, a and b) for 'localized genes' and genes from the bank are in full agreement, indicating that the former set is representative of the latter. We have then used the data (i) and the correlation (ii) to estimate the distribution of genes in isochore families. We have found that 34% of the genes are located in the GC-poor isochores (which represent 62% of the genome), 38% in the GC-rich isochores (31% of the genome) and 28% in the GC-richest isochores (3% of the genome). There is, therefore, a compositional gradient of gene concentration in the human genome. The gene density in the GC-richest 3% of the genome is about eight times higher than in the GC-rich 31%, and about 16 times higher than in the GC-poorest 62%.
Base Composition↗
Vaccination against polyoma virus (PyV) tumors using vaccinia-PyV recombinants: a major tumor-specific transplantation antigen (TSTA) epitope resides within the C-terminal segment of middle-T protein.
We previously reported that inoculation of rats with live vaccinia virus (VV) recombinants VVpyMT, VVpyLT expressing either the middle-T (MT) or large-T (LT) proteins of polyomavirus (PyV) can elicit immunity to challenge with syngeneic PyV-tumor cells. We now report the results of cross-vaccination studies. VVpyMT was ineffective against cells expressing LT protein but prevented development of MT-expressing cells. Conversely, the VVpyLT was ineffective against MT-expressing cells. In the two experiments performed, tumor growth enhancement rather than retardation was observed in VVpyLT-vaccinated animals receiving PyV-LT (FRLTI) challenge tumor cells. To determine the location of the major TSTA within MT, a further VV recombinant (VVpyMT/Cfr) was constructed that expresses only the unique C-terminal segment of MT. VVpyMT-Cfr and VVpyMT were equally effective in eliciting tumor immunity, indicating the presence of a major TSTA epitope within the unique C-terminal region of MT.
Amino Acid Sequence↗
hSP, the domain-duplicated homolog of pS2 protein, is co-expressed with pS2 in stomach but not in breast carcinoma.
Approximately 50% of human breast tumors secrete a small cysteine-rich protein, pS2, of unknown function. pS2 protein was recently found to be homologous to a porcine protein with hormonogastric activity, pancreatic spasmolytic polypeptide (PSP), in which the 5-cysteine domain present in pS2 is tandemly duplicated. We have characterized cDNA species encoding PSP and its human and mouse counterparts, hSP and mSP. We show that hSP and pS2 are separately encoded in the genome, and that the two proteins are co-expressed in normal stomach epithelium. However, expression of hSP was not detected in breast tumors. Computer analysis revealed that the pattern of conserved cysteine residues in hSP and pS2, the P domain, is present at the N termini of two other mammalian proteins, intestinal sucrase-isomaltase and lysosomal alpha-glucosidase.
Amino Acid Sequence↗
Codon usage changes and sequence dissimilarity between human and rat.
This paper reports on the relationship between the number of silent differences and the codon usage changes in the lineages leading to human and rat. Examination of 102 pairs of homologous genes gives rise to four main conclusions: (1) We have previously demonstrated the existence of a codon usage change (called the minor shift) between human and rat; this was confirmed here with a larger sample. For genes with extreme C & G frequencies, the C & G level in the third codon position is less extreme in rat than in human. (2) Protein similarity and percentage of positive differences are the two main factors that discriminate homologous genes when characterized by differences between rat and human. By definition, positive differences result from silent changes between A or T and C or G with a direction implying a C & G content variation in the same direction as the overall gene variation. (3) For genes showing both codon usage change and low protein similarity, a majority of amino acid replacements contributes to C & G level variation in positions I and II in the same direction as the variation in position III. This is thus a new example of protein evolution due to constraints acting at the DNA level. (4) In heavy isochores (high C & G content) no direct correlation exists between codon usage change (measured by the dissymmetry of differences) and silent dissimilarity. In light isochores the opposite situation is observed: modification of codon usage is associated with a high synonymous dissimilarity. This result shows that, in some cases, modification of constrains acting at the DNA level could accelerate divergence between genomes.
Animals↗
Localization of P elements, copy number regulation, and cytotype determination in Drosophila melanogaster.
Seventeen highly-inbred lines of Drosophila melanogaster extracted from an M' strain (in the P/M system of hybrid dysgenesis) were studied for their cytotype and the number and chromosomal location of complete and defective P elements. While most lines were of M cytotype, three presented a P cytotype (the condition that represses P-element activity) and one was intermediate between M and P. All lines were found to possess KP elements and only eight to bear full-sized P elements. Only the lines with full-sized P elements showed detectable changes in their P-insertion pattern over generations; their rates of gain and of loss of P-element sites were equal to 0.12 and 0.09 per genome, per generation, respectively. There was no correlation between these two rates within lines, suggesting independent transpositions and excisions in the inbred genomes. The results of both Southern blot analysis and in situ hybridization of probes made from left and right sides of the P element strongly suggested the presence of a putative complete P element in region 1A of the X chromosome in the three lines with a P cytotype; the absence of P copy in this 1A region in lines with an M cytotype, favours the hypothesis that the P element inserted in 1A could play a major role in the P-cytotype determination. Insertion of a defective 2 kb P element was also observed in region 93F in 9 of the 13 M lines. The regulation of the P-element copy number in our lines appeared not to be associated with the ratio of full-length and defective P elements.
Animals↗
Vaccination against tumor cells expressing breast cancer epithelial tumor antigen.
Ninety-one percent of breast tumors aberrantly express an epithelial tumor antigen (ETA) identified by monoclonal antibody H23. Vaccinia virus recombinants expressing tumor antigens have considerable promise in the active immunotherapy of cancer, and we have evaluated the potential of vaccinia recombinants expressing the secreted (S) and cell-associated (transmembrane, T) forms of H23 ETA to elicit immunity to tumor cells expressing ETA. Tumorigenic ras-transformed Fischer rat fibroblast lines FR-S and FR-T, expressing the S or T form of H23 ETA, respectively, were constructed for use in challenge experiments. Expression of H23 ETA in these lines was confirmed by Western blotting and immunofluorescence. When challenged by subcutaneous seeding of tumor cells, 97% (FR-S) and 91% (FR-T) of syngeneic Fischer rats rapidly developed tumors that failed to regress. Vaccination with recombinant vaccinia virus expressing ETA-T prior to challenge prevented tumor development in 82% of animals seeded with FR-T cells but in only 61% of animals seeded with FR-S. The vaccinia recombinant expressing the S form was a less effective immunogen, and vaccination protected only 29-30% of animals from developing tumors upon challenge with either FR-S or -T cells. The increased immunogenicity of the recombinant expressing ETA-T was reflected in elevated levels of ETA-reactive antibody in vaccinated animals, confirming that secreted antigens expressed from vaccinia virus are less effective immunogens than their membrane-associated counterparts.
Animals↗
A ubiquitous mammalian expression vector, pHMG, based on a housekeeping gene promoter.
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Animals↗
alpha-DNA X: alpha and beta tetrathymidilates covalently linked to oxazolopyridocarbazolium (OPC): comparative stabilization of oligo beta-[dT]:oligo beta-[dA] and oligo alpha-[dT]:oligo beta-[dA] duplexes by the intercalating agent.
The influence of the intercalating oxazolopyridocarbazolium (HOPC) on the stabilization of modified oligonucleotides: alpha-T4c5OPC or beta-T4c5OPC associated to beta-oligo (dA) was studied. It appears that the situation is different from what has been observed for the interaction of these modified oligonucleotides with poly (rA). The higher free energy of formation of the alpha-T4c5OPC :beta-oligo(dA), when compared to beta-T4c5OPC, is essentially due to the overall stability added to this system by the intercalator. This enhanced stability comes from a higher number of binding sites of HOPC for the alpha:beta duplex together with a lower van't Hoff energy of formation of the alpha:beta duplex.
Carbazoles↗
Interactions between transposable elements for insertion in the Drosophila melanogaster genome.
Using in situ hybridization to polytene salivary gland chromosomes, we have registered the co-occurrences of insertions of the four mobile elements, copia, mdg-1, I and P in the whole genomes of 17 highly-inbred lines of Drosophila melanogaster (the insertions in the centromeric regions were excluded); these elements differ in structure, DNA sequence and profile of developmental transcription. The mdg-1 and P elements tend to avoid each other on the X chromosomes but not on the autosomes; copia and mdg-1, two copia-like elements, show an excess of co-occurrences on the 2L and 3R chromosome arms but not on the X chromosomes. The pairs mdg-1/I, I/copia, I/P and copia/P do not show any kind of interaction. Populational studies are thus necessary to obtain complete accurate information on interactions between transposable elements for their sites of insertion in a genome.
Animals↗
Poly(rA) binding of alpha-anomeric and beta-anomeric tetrathymidylates covalently linked to an intercalating oxazolopyridocarbazolium. Determination of the binding parameters.
We have investigated by means of absorbance measurements at 310 nm the binding of alpha-anomeric or beta-anomeric tetrathymidylates covalently substituted at their 3' end by an intercalating agent (oxazolopyridocarbazolium), to poly(rA). Taking into account the strong autoaggregation of the free ligands, we have derived the binding parameters corresponding to the [alpha] and the [beta] ligands. The affinity of the alpha-anomer for poly(rA) is higher than the affinity of the beta-anomer in accordance with the Tm studies conducted on such a system.
Alkaloids↗
The compositional distribution of coding sequences and DNA molecules in humans and murids.
The compositional distributions of coding sequences and DNA molecules (in the 50-100-kb range) are remarkably narrower in murids (rat and mouse) compared to humans (as well as to all other mammals explored so far). In murids, both distributions begin at higher and end at lower GC values. A comparison of homologous coding sequences from murids and humans revealed that their different compositional distributions are due to differences in GC levels in all three codon positions, particularly of genes located at both ends of the distribution. In turn, these differences are responsible for differences in both codon usage and amino acids. When GC levels at first + second codon positions and third codon positions, respectively, of murid genes are plotted against corresponding GC levels of homologous human genes, linear relationships (with very high correlation coefficients and slopes of about 0.78 and 0.60, respectively) are found. This indicates a conservation of the order of GC levels in homologous genes from humans and murids. (The same comparison for mouse and rat genes indicates a conservation of GC levels of homologous genes.) A similar linear relationship was observed when plotting GC levels of corresponding DNA fractions (as obtained by density gradient centrifugation in the presence of a sequence-specific ligand) from mouse and human. These findings indicate that orderly compositional changes affecting not only coding sequences but also noncoding sequences took place since the divergence of murids. Such directional fixations of mutations point to the existence of selective pressures affecting the genome as a whole.
Amino Acid Sequence↗
High codon-usage changes in mammalian genes.
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Animals↗
Alpha-DNA. IV: Alpha-anomeric and beta-anomeric tetrathymidylates covalently linked to intercalating oxazolopyridocarbazole. Synthesis, physicochemical properties and poly (rA) binding.
A new set of molecules made of an intercalating agent (oxazolopyridocarbazole, OPC) covalently linked through a polymethylene chain of various length to the 3' end of alpha-anomeric or beta-anomeric tetradeoxynucleotides (alpha- or beta-T4) have been synthesized. The beta-thymidylate modified compound (beta-T4C5OPC) is able to interact with the complementary sequence, beta-poly (rA); this interaction is strongly stabilized compared to the parent compound, beta-oligo(dT)4 and is specific for poly (rA). The molecule synthesized from the unnatural alpha-anomer, alpha-T4C5OPC, is also able to interact with poly (rA) leading to the formation of an alpha-beta hybrid stabilized by the energy provided by the OPC moiety. The stoechiometry of the binding reaction shows that an A-T pairing occurs in the alpha-beta heterohybrids. Tm studies reveal that the alpha-beta heterohybrids are more stable than their beta-beta counterparts.
Base Sequence↗
Statistical method for predicting protein coding regions in nucleic acid sequences.
Protein coding regions of a genome fragment can be mathematically predicted by studying variations in the statistical properties or by searching the signals characteristic of the junctions between the coding and non-coding regions. We propose here a new statistical method using correspondence analysis. This method does not use any reference codon set but takes into account the codon usage homogeneity along the studied genome fragment. Comparison with previously published methods especially the 'codon usage method' of Staden has been made, and two examples are presented here. Applications to analysis of prokaryotic operon and eukaryotic split genes are also discussed. Use of the method has also shown two structures not previously described: i) in the human prt gene, a strong triplet structure exists in a non-coding region; ii) in the human tp-a codon usage is not uniform between the different exons.
Algorithms↗