Biomedical subjects

R Guyot

Publications and source records attributed to R Guyot.

10 recordsLinked to original sources

PubMed2004

Diffusion of levofloxacin into bone and synovial tissues.

OBJECTIVES: The degree of penetration of an antibiotic into the infected site is an important determinant of therapeutic success. Levofloxacin is widely used in the treatment of serious infections. However, there are only few studies concerning its diffusion into bone tissue and none concerning its diffusion into synovial tissue. Our objective was to quantify levofloxacin bone and synovial tissue penetration and to compare our data with the breakpoint for susceptible organisms. PATIENTS AND METHODS: In an open-label study, 12 subjects who were undergoing elective total hip replacement received a single, parenteral, 500 mg dose of levofloxacin. Plasma, cortical and cancellous bone, and synovial tissue samples were collected a mean of 1.2 h later and analysed by a validated HPLC method. RESULTS: The mean +/- S.D. plasma concentration of levofloxacin at the time of bone removal was 7.5 +/- 1.3 mg/L. The levofloxacin concentrations were 7.4 +/- 2.2 mg/kg in cancellous bone tissue and 3.9 +/- 1.2 mg/kg in cortical bone tissue. The levofloxacin concentration was 8.9 +/- 2.1 mg/kg in synovial tissue. The mean +/- S.D. ratios of levofloxacin concentration in bone and plasma (bone/plasma) were 1.0 +/- 0.4 for cancellous bone tissue and 0.5 +/- 0.1 for cortical bone tissue. The ratio of levofloxacin concentration in synovial tissue and plasma (synovial tissue/plasma) was 1.2 +/- 0.4. CONCLUSIONS: The concentrations of levofloxacin achieved in cancellous and cortical bone tissue and in synovial tissue are greater than the breakpoint for susceptible organisms, which is < or =2 mg/L.

Aged↗

PubMed2001

Identification of 66 box C/D snoRNAs in Arabidopsis thaliana: extensive gene duplications generated multiple isoforms predicting new ribosomal RNA 2'-O-methylation sites.

Dozens of box C/D small nucleolar RNAs (snoRNAs) have recently been found in eukaryotes (vertebrates, yeast), ancient eukaryotes (trypanosomes) and archae, that specifically target ribosomal RNA sites for 2'-O-ribose methylation. Although early biochemical data revealed that plant rRNAs are among the most highly ribomethylated in eukaryotes, only a handful of methylation guide snoRNAs have been characterized in this kingdom. We report 66 novel box C/D snoRNAs identified by computational screening of Arabidopsis genomic sequences that are expressed in vivo from either single genes, 17 different clusters or three introns. At the structural level, many box C/D snoRNAs have dual antisense elements often matching rRNA regions close to each other on the rRNA secondary structure, which is reminiscent of their archaeal counterparts. Remarkable specimens are found that display two antisense elements having the potential to form an extended snoRNA-rRNA duplex of 23 to 30 nt, in line with the hypothetical function of box C/D snoRNAs in pre-rRNA folding or chaperoning. In contrast to other species, many Arabidopsis snoRNAs are found in multiple isoforms mainly resulting from two different mechanisms: large chromosomal duplications and small tandem duplications producing polycistronic genes. The discovery of numerous different snoRNAs, some of them arising from common ancestors, provide new insights to understand snoRNAs evolution and the birth of new rRNA methylation sites in plants and other organisms.

Arabidopsis↗

PubMed2001

The organization of cytoplasmic ribosomal protein genes in the Arabidopsis genome.

Eukaryotic ribosomes are made of two components, four ribosomal RNAs, and approximately 80 ribosomal proteins (r-proteins). The exact number of r-proteins and r-protein genes in higher plants is not known. The strong conservation in eukaryotic r-protein primary sequence allowed us to use the well-characterized rat (Rattus norvegicus) r-protein set to identify orthologues on the five haploid chromosomes of Arabidopsis. By use of the numerous expressed sequence tag (EST) accessions and the complete genomic sequence of this species, we identified 249 genes (including some pseudogenes) corresponding to 80 (32 small subunit and 48 large subunit) cytoplasmic r-protein types. None of the r-protein genes are single copy and most are encoded by three or four expressed genes, indicative of the internal duplication of the Arabidopsis genome. The r-proteins are distributed throughout the genome. Inspection of genes in the vicinity of r-protein gene family members confirms extensive duplications of large chromosome fragments and sheds light on the evolutionary history of the Arabidopsis genome. Examination of large duplicated regions indicated that a significant fraction of the r-protein genes have been either lost from one of the duplicated fragments or inserted after the initial duplication event. Only 52 r-protein genes lack a matching EST accession, and 19 of these contain incomplete open reading frames, confirming that most genes are expressed. Assessment of cognate EST numbers suggests that r-protein gene family members are differentially expressed.

Animals↗

PubMed2000

Extensive duplication and reshuffling in the Arabidopsis genome.

Systematic analysis of the Arabidopsis genome provides a basis for detailed studies of genome structure and evolution. Members of multigene families were mapped, and random sequence alignment was used to identify regions of extended similarity in the Arabidopsis genome. Detailed analysis showed that the number, order, and orientation of genes were conserved over large regions of the genome, revealing extensive duplication covering the majority of the known genomic sequence. Fine mapping analysis showed much rearrangement, resulting in a patchwork of duplicated regions that indicated deletion, insertion, tandem duplication, inversion, and reciprocal translocation. The implications of these observations for evolution of the Arabidopsis genome as well as their usefulness for analysis and annotation of the genomic sequence and in comparative genomics are discussed.

Arabidopsis↗

PubMed2000

Alpha(2) adrenoceptors regulate proliferation of human intestinal epithelial cells.

BACKGROUND AND AIMS: Previous studies on rodents have suggested that catecholamines stimulate proliferation of the intestinal epithelium through activation of alpha(2) adrenoceptors located on crypt cells. The occurrence of this effect awaits demonstration in humans and the molecular mechanisms involved have not yet been elucidated. Here, we examined the effect of alpha(2) agonists on a clone of Caco2 cells expressing the human alpha(2A) adrenoceptor. METHODS: Cells were transfected with a bicistronic plasmid containing the alpha2C10 and neomycin phosphotransferase genes. G418 resistant clones were assayed for receptor expression using radioligand binding. Receptor functionality was assessed by testing its ability to couple Gi proteins and to inhibit cAMP production. Mitogen activated protein kinase (MAPK) phosphorylation was followed by western blot, and cell proliferation was estimated by measuring protein and DNA content. RESULTS: Permanent transfection of Caco2 cells allowed us to obtain a clone (Caco2-3B) expressing alpha(2A) adrenoceptors at a density similar to that found in normal human intestinal epithelium. Caco2-3B retained morphological features and brush border enzyme expression characteristic of enterocytic differentiation. The receptor was coupled to Gi2/Gi3 proteins and its stimulation caused marked diminution of forskolin induced cAMP production. Treatment of Caco2-3B with UK14304 (alpha(2) agonist) induced a rapid increase in the phosphorylation state of MAPK, extracellular regulated protein kinase 1 (Erk1), and 2 (Erk2). This event was totally abolished in pertussis toxin treated cells and in the presence of kinase inhibitors (genistein or PD98059). It was unaffected by protein kinase C downregulation but correlated with a transient increase in Shc tyrosine phosphorylation. Finally, sustained exposure of Caco2-3B to UK14304 resulted in modest but significant acceleration of cell proliferation. None of these effects was observed in the parental cell line Caco2. CONCLUSION: The results obtained in the present study support a regulatory role for alpha(2) adrenoceptors in intestinal cell proliferation.

Adrenergic alpha-2 Receptor Agonists↗

PubMed1969