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Biomedical subjects

C Gautier

Publications and source records attributed to C Gautier.

At least 73 records · Page 4Linked to original sources

[Benign cutaneous lymphocytoma of the breast areola and Erythema chronicum migrans: a pathognomonic association of Lyme disease].

BACKGROUND: Clinical manifestations of Lyme disease are mainly cutaneous, neurologic, cardiac and/or located joints. Some dermatologic manifestations are more specific. CASE REPORT: An eight year-old-girl was examined because she suffered from a nodular lesion located on the left breast areola which appeared 3 months earlier. This lesion was associated with an expanding erythematous annular lesion located on the anterior face of thorax and left axillary area, without any lymphadenopathy. The association of this cutaneous lymphocytoma and erythema chronicum migrans was suggestive of Borellia infection despite absence of previous tick bite. Serologic tests (indirect immunofluorescence) were negative, but both lesions disappeared within 2 weeks with ceftriaxone, 50 mg/kg/day. CONCLUSIONS: This association is pathognomonic of Lyme disease; serologic tests may be found negative in the early stages of disease.

Breast↗

Hydrophobicity, expressivity and aromaticity are the major trends of amino-acid usage in 999 Escherichia coli chromosome-encoded genes.

Multivariate analysis of the amino-acid compositions of 999 chromosome-encoded proteins from Escherichia coli showed that three main factors influence the variability of amino-acid composition. The first factor was correlated with the global hydrophobicity of proteins, and it discriminated integral membrane proteins from the others. The second factor was correlated with gene expressivity, showing a bias in highly expressed genes towards amino-acids having abundant major tRNAs. Just as highly expressed genes have reduced codon diversity in protein coding sequences, so do they have a reduced diversity of amino-acid choice. This showed that translational constraints are important enough to affect the global amino-acid composition of proteins. The third factor was correlated with the aromaticity of proteins, showing that aromatic amino-acid content is highly variable.

Amino Acids↗

Demonstration of argininosuccinate synthetase activity associated with mitochondrial membrane: characterization and hormonal regulation.

Argininosuccinate synthetase (AS) is the third enzyme in ureogenesis, it catalyses the reaction of condensation of citrulline and aspartate into argininosuccinate. In the present report, we described the first characterization of AS within the outer membrane of rat liver mitochondria. Mitochondria-associated AS displayed the same kinetic characteristics as the cytoplasmic enzyme, but was found to be thermostable while cytoplasmic AS was not. The evolution of the co-location of AS was analyzed during ontogenesis. Total AS activity increased throughout rat fetal development. Simultaneously, the subcellular distribution of the enzyme has changed. AS activity was mainly mitochondrial in fetal and new-born liver liver and cytoplasmic in adult rat liver. The variation in subcellular distribution of AS may be due to the dramatic changes in hormonal levels that occur during this period. The role of corticosteroid and pancreatic hormones was studied. During fetal period, corticosteroid hormones induced an increase in mitochondria-associated AS activity. This was prevented by insulin. Glucagon did not modify total AS activity but reduced mitochondrial AS activity, meanwhile, a comparable increase in cytoplasmic AS activity was observed. One may hypothesize that glucagon may participate in the transfer of mitochondrial enzyme into the cytosol.

Adrenal Cortex Hormones↗

Immunohistochemical localization of transforming growth factor-beta 1 in the fetal and neonatal rat testis.

The localization of transforming growth factor-beta 1 in the fetal and neonatal rat testis (from day 13.5 of fetal life to postnatal day 20) was investigated by an immunohistochemical staining method employing a polyclonal anti-TGF-beta 1 antibody that does not cross react with either TGF-beta 2 or TGF-beta 3. In testis and mesonephros tissue, immunostaining for TGF-beta 1 was undetectable on fetal day 13.5 and appeared exclusively in the primordial Sertoli cells on fetal day 14.5. Staining in Sertoli cells was still clearly observed on days 15.5 and 16.5 of fetal life and became faint from fetal day 18.5 onwards. In fetal Leydig cells, a positive reaction for TGF-beta 1 appeared on day 16.5 and became very intense during late fetal life. After birth, fetal-type Leydig cells, which were still observed on postnatal days 4 and 20, also exhibited a very strong immunostaining for TGF-beta 1, whereas adult-type Leydig cells, observed on day 20, showed a slight staining. No immunoreactivity for TGF-beta 1 was found in germ cells and peritubular cells on any day studied. In conclusion, TGF-beta 1 is present very early in the fetal rat testis and its prevailing localization shows age-related changes, which suggests that this factor plays an autocrine/paracrine role in the regulation of testicular function and differentiation, during early development.

Animals↗

Population dynamics of the copia, mdg1, mdg3, gypsy, and P transposable elements in a natural population of Drosophila melanogaster.

The insertion site polymorphism of the copia, mdg1, mdg3, gypsy, and P transposable elements was analysed by in situ hybridization to the polytene chromosomes in genomes of males from a natural population of Drosophila melanogaster. Parameters of various theoretical models of the population biology of transposable elements were estimated from our data, and different hypotheses explaining TE copy number containment were tested. The copia, mdg1 and gypsy elements show evidence for a deficiency of insertions on the X chromosomes, a result consistent with selection against the mutational effects of insertions. On the contrary, mdg3 and P copy numbers fit a neutral model with a balance between regulated transposition and excisions. There is no strong evidence of a systematic accumulation of elements in the distal and proximal regions of the chromosomes where crossing over and ectopic exchanges are reduced. For all chromosome arms but 3L, however, the TE site density increases from the proximal to the distal parts of the chromosomes (the centromeric regions were excluded in this analysis) with sometimes a sharp decrease in density at the extreme tip, following in part the exchange coefficient. The way the copy number of TEs is contained in genomes depends thus on the element considered, and on various forces acting simultaneously, indicating that models of TE dynamics should include details of each element.

Animals↗

High rate of movement of one (mdg3) out of four transposable elements in a natural population of Drosophila melanogaster.

We have analysed by in situ hybridization the insertion site polymorphism of the copia, mdg1, mdg3, and P transposable elements in diploid genomes of wild males from a natural population of Drosophila melanogaster. The values of observed average degree of individual heterozygosity for all elements except mdg3 deviate statistically from the values expected by site frequencies, revealing a tendency toward homozygosity as if drift or a structuration in the population was operating. The high degree of heterozygosity for mdg3 which in addition does not deviate from the expected value, suggests that recent high rate of movements has strongly countered the population host effect on this element. Hence, heterozygosity for TEs may well reflect the history of the population, and reveals temporary high rate of site movement existing in natural populations.

Animals↗

[Aspects and value of MRI in the diagnosis and follow-up of common microbes infectious spondylodiscitis. Apropos of 25 clinically and biologically suspected patients].

This work is about 25 patients clinically and biologically suspected of spondylodiscitis (27 levels). All of them had a MRI exam before disco-vertebral needle biopsy and treatment. The results are compared to those of literature. Each infectious spondylitis case (19 cases) had a new MRI exam each three months. This study conclude to the great sensibility of MRI (89%) in the diagnosis of infectious spondylitis and to the limited interest of it in the follow-up of spondylodiscitis.

Adolescent↗

Strong conservation of non-coding sequences during vertebrates evolution: potential involvement in post-transcriptional regulation of gene expression.

Comparison of nucleotide sequences from different classes of vertebrates that diverged more than 300 million years ago, revealed the existence of highly conserved regions (HCRs) with more than 70% similarity over 100 to 1450 nt in non-coding parts of genes. Such a conservation is unexpected because it is much longer and stronger than what is necessary for specifying the binding of a regulatory protein. HCRs are relatively frequent, particularly in genes that are essential to cell life. In multigene families, conserved regions are specific of each isotype and are probably involved in the control of their specific pattern of expression. Studying HCRs distribution within genes showed that functional constraints are generally much stronger in 3'-non-coding regions than in promoters or introns. The 3'-HCRs are particularly A + T-rich and are always located in the transcribed untranslated regions of genes, which suggests that they are involved in post-transcriptional processes. However, current knowledge of mechanisms that regulate mRNA export, localisation, translation, or degradation is not sufficient to explain the strong functional constraints that we have characterised.

Animals↗

Silent substitutions in mammalian genomes and their evolutionary implications.

An analysis of silent substitutions in pairwise comparisons of homologous genes from different mammals has shown that, in spite of individual fluctuations, their frequencies (which are very strongly correlated with the frequency of substitutions per synonymous site calculated according to Li et al. 1985) do not vary, on the average, with the GC levels of silent positions. This holds in the general case, in which silent positions of pairs of homologous genes share the same composition, namely in the human/other primates, human/artiodactyls, and in the mouse/rat pairs, as well as in the special cases in which the composition of silent positions are different, namely in the human/rabbit and the human/rat (or human/mouse) pairs. A slightly lower frequency found for low GC values in the human/bovine and human/pig pairs seems to be due to the specific gene samples used. These results contradict the previously claimed existence of differences in mutation rates and of mutational biases in third codon positions of coding sequences located in different isochores of mammalian genomes. They also imply that the variations in nucleotide precursor pools through the cell cycle and the differences in replication timing, or in repair efficiency, which were reported for different isochores, do not lead, as claimed, to differences in mutation rates, not in mutational biases in mammals. The differences claimed appear to be due to using small gene samples when individual fluctuations from gene to gene are relatively large.

Animals↗

Stimulatory effect of follicle-stimulating hormone on basal and luteinizing hormone-stimulated testosterone secretions by the fetal rat testis in vitro.

The in vitro effect of FSH on testosterone secretion by the fetal rat testis was studied. Testes were cultured in the presence or absence of either commercial human (h) FSH (Metrodine; 200 mIU/ml) or recombinant hFSH (200 mIU/ml) for 3 days and with 100 ng/ml ovine LH during the last 4 h of culture. To avoid a stimulatory effect by the 0.4% LH that contaminates Metrodine, the cultures were performed in the presence of a monoclonal anti-hLH beta antibody and with a concentration of Metrodine that had no short term stimulatory effect on testosterone production by the fetal testes in vitro. Metrodine treatment had a positive long term effect on both basal and LH-stimulated testosterone secretion by fetal testes explanted on days 18.5, 20.5, and 22.5 postconception, which was abolished by the addition of a monoclonal anti-hFSH beta antibody. LH-free recombinant FSH also augmented basal and LH-stimulated testosterone secretion of testes explanted on days 13.5, 14.5, and 18.5 postconception. The positive effect of recombinant hFSH appeared during the second day of treatment with day 14.5 and 18.5 testes and on the third day of treatment with day 13.5 testes. As it is widely accepted that FSH receptors are exclusively localized on Sertoli cells, these results suggest that on or before day 15.5 of fetal life, 1) Sertoli cells are able to respond to FSH, 2) Sertoli cells can produce factors that are able to act on Leydig cell function, and 3) Leydig cells are sensitive to FSH-induced Sertoli cell factors. In conclusion, this study points out a potential paracrine control of fetal Leydig cell function and/or differentiation by fetal Sertoli cells as soon as fetal Leydig cells differentiate.

Animals↗

Object-oriented knowledge bases for the analysis of prokaryotic and eukaryotic genomes.

The amount of biological sequences introduced in the general collections, and the growing complexity of the biological knowledge require the construction of models to formalize this knowledge and particularly the relationships between several data types. Two examples of such situations are presented here, they result from the biological research lead in our team in the field of molecular evolution. ColiGene is a modelling of E. coli genetics devoted to the analysis of relationships between genomic sequences and gene expressivity. MultiMap implements a new formalization of genome maps allowing manipulation of "maps of maps" in two species. Application of ColiGene and MultiMap are not restricted to molecular evolution and, for instance, MultiMap offers new capabilities for infering data on a genome from knowledge on another species. This could be essential for many mapping projects (human, mouse but also other mammals like pig). Development and implementation of those models have been done using an object-oriented knowledge base management system (SHIRKA) interfaced with a dedicated genomic data base management system (ACNUC). Graphical interfaces have been designed to give an environment similar to the biological representations used by biologists.

Animals↗

Building large knowledge bases in molecular biology.

Large scale genome sequencing projects are now producing hugh amounts of data which can be readily stored and managed within data base management systems, and analyzed using dedicated software packages. The results of these analyzes should also be stored with the input DNA sequences. The increasing complexity and size of the objects to be described and managed have led biologists to rely on advanced data models such as the object-oriented model. As a joint effort between our computer science and molecular biology research projects, the knowledge bases we have developed in molecular genetics have shown however that the basic object-oriented model is not fully adapted to the complexity of some biological situations encountered. Advanced descriptive capabilities, provided only by knowledge models originated from the AI field, are required. Composite or evolving objects, multiple viewpoints, constraints, tasks and methods, textual annotations are some examples of such capabilities. They are illustrated by biological situations for which they appeared to be necessary. Supporting powerful reasoning mechanisms (e.g. object classification, constraint propagation or qualitative simulators), they allow the development of large knowledge bases in molecular biology. These knowledge bases are expected to become the adequate support for co-operative distributed research efforts.

Artificial Intelligence↗

ColiGene: object-centered representation for the study of E coli gene expressivity by sequence analysis.

ColiGene is an object-centered knowledge base for the study of gene expressivity in Escherichia coli by DNA sequence analysis. This system was developed with the knowledge base management system SHIRKA. Objects represented in ColiGene are biological structures such as genes or regulatory signals. They are organized in a hierarchical structure of classes, subclasses and instances. Navigation through the knowledge base and the building of queries are made using a graphical interface. The base is coupled with the data base ACNUC which structures a specialized collection of sequences: EcoSeq. Several tools are also associated to ColiGene, either for sequence analysis or for a more general purpose. Some biological results have been obtained using ColiGene which are summarized here.

Artificial Intelligence↗

Value of axillary dissection in addition to lumpectomy and radiotherapy in early breast cancer. The Breast Carcinoma Collaborative Group of the Institut Curie.

Axillary dissection in early breast cancer remains controversial because of its substantial side-effects and because its value with respect to recurrence or survival has not been unequivocally proven. Between 1982 and 1987, 658 patients were included in a prospective randomised comparison of lumpectomy alone with lumpectomy plus axillary dissection. All patients had a unilateral breast tumour not exceeding 3 cm in diameter and lymph-node involvement or metastases. Radiation therapy was given to both groups. The two groups of patients were similar with respect to mean age, TNM stage, and presence of hormonal receptors. Median follow-up was 54 months. 5-year survival of the patients was 94.2% (95% Cl: 92.1-96.4). There was a significant advantage in survival in the axillary dissection group (p = 0.014). Recurrence of tumour in the breast was similar in the two groups but visceral metastases, supraclavicular metastases, and lymph-node recurrences were less frequent in the axillary dissection group. Survival was related to the age of the patients (p = 0.005), the presence of positive nodes (p = 0.006), the histological grading (p less than 0.0001), and the presence of hormonal receptors (progesterone p = 0.0008, oestrogen p less than 0.0001). Treatment-adjusted relative risk was 2.4 (95% Cl: 1.3-4.2). The findings show that axillary dissection is justified for treatment of small breast cancers, although whether the better survival is due to axillary clearance itself or to adjuvant treatment for lymph-node involvement is unclear.

Adult↗

4-Thiocellooligosaccharides. Their synthesis and use as ligands for the separation of cellobiohydrolases of Trichoderma reesei by affinity chromatography.

4-Aminophenyl 1,4-dithio-beta-cellobioside (6) was obtained by treatment of methyl 2,3,6-tri-O-benzoyl-4-O-triflyl-alpha-D-galactopyranoside with the sodium salt of 1-thio-beta-D-glucopyranose, followed by acetolysis and glycosylation of the corresponding bromide with 4-aminobenzenethiol and subsequent deacylation. A similar synthesis starting with the 1-thiolate of 1,4-dithio-beta-cellobiose led to the trisaccharide 4-aminophenyl 1,4,4'-trithiocellotrioside (16). The 4-acetamidophenyl di- and tri-thiocellooligosaccharides were found to be excellent competitive inhibitors of the hydrolysis of 4-methylumbelliferyl beta-lactoside with respective Ki values of 25 and 6.5 mM. The two 4-aminophenyl oligosaccharides 6 and 16 were coupled to CH-Sepharose 4B, and the affinity gels were used for the purification of cellobiohydrolases from a crude commercial cellulolytic extract of T. reesei. Cellobiohydrolases I or II were selectively desorbed from gels bearing ligands 6 and 16.

Carbohydrate Sequence↗

Aortic false aneurysms after prosthetic reconstruction of the infrarenal aorta.

False aneurysm of the infrarenal aorta was found at the site of proximal anastomosis in 13 patients after vascular reconstruction for lower limb arterial disease. The grafts involved were aortoprosthetic in one patient, aortobiiliac in two patients, and aortobifemoral in 10 patients. They had been implanted eight years prior to reoperation on the average (range six months to 15 years). False aneurysm was diagnosed because of abdominal pain in four cases, embolism in two cases, intestinal hemorrhage in one case, and during routine sonographic or computed tomographic (CT) scan surveillance in the six other cases. Femoral false aneurysm was associated in eight of 10 cases with femoral anastomoses. Aortic false aneurysms were repaired by interposition of a prosthetic tube between the infrarenal aorta and the original prosthetic graft in 11 cases and by changing the aortobifemoral graft in two cases. In one further case, repair was accomplished by implanting an aortobifemoral prosthetic graft laterally on a prosthetic tube interposed between the infrarenal aorta and the body of the original prosthetic graft, which continued to irrigate the internal iliac arteries. There was no mortality. Thrombosis of a prosthetic branch occurred in one case and was treated by thrombectomy. One patient underwent reoperation for intestinal obstruction. Two others had distal embolism responsible for toe necrosis. Anastomotic false aneurysms should be looked for routinely during the surveillance of prosthetic grafts implanted on the infrarenal aorta, especially when femoral false aneurysm is found. Preservation of pelvic vascularization must be an integral part of management.

Aged↗

Changes in argininosuccinate lyase gene expression in the rat liver during development.

Expression of the hepatic enzyme argininosuccinate lyase (ASL), one of the urea cycle enzymes, was analyzed during the perinatal period in the rat. To this end, ASL was purified, an ELISA assay was established to quantify the enzyme protein and a cDNA clone was used to measure the amount of specific mRNA in the liver in various stages of development. During the last few days of fetal life, both enzyme and hybridizable RNA were present at levels far below those measured in the fully differentiated adult liver. Just after birth, they increased rapidly and the mRNA accumulation, particularly, could result from an enhanced rate of transcription as suggested by the experiment with actinomycin D. This postnatal shift in ASL expression was also linked to adrenal activation at birth, as shown by adrenalectomy. However, the extent to which the ASL protein accumulated after birth appeared to be limited when compared to mRNA accumulation, suggesting control mechanisms at the translational level. Thus, during the perinatal period of the rat, both transcriptional and translational control might be implicated in the expression of the ASL gene.

Animals↗

Development and hormonal control of thioredoxin and the thioredoxin-reductase system in the rat liver during the perinatal period.

The development and hormonal regulation of thioredoxin and of the thioredoxin-reductase system were investigated during the perinatal period in rat liver. An immunological procedure was developed in order to quantify thioredoxin in fetal and neonatal hepatocytes. Both immunoreactive thioredoxin and thioredoxin-reductase activity appeared on day 16.5 of pregnancy. The level of immunoreactive thioredoxin increased during the late fetal period, and its level was the same 24 h after birth. Moreover, its development was not subjected to hormonal regulation by corticosteroids and glucagon. In contrast, thioredoxin-reductase activity increased 3 times during the late fetal period and presented a marked increase 24 h after birth. In the absence of glucocorticoids there was no increase in the level of thioredoxin reductase, while administration of hydrocortisone acetate and glucagon to fetuses prematurely evoked its activity. This study suggests that if thioredoxin acts physiologically, this activity is related to the state of reduction of the molecule rather than to the total concentration in the liver.

Animals↗