[Problems related to nearby general pediatric services in the management of children with cancer].
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Cancer Care Facilities↗
Biomedical subjects
M Jullien
Publications and source records attributed to M Jullien.
Epidemiological changes in hepatitis C virus genotypes in France: evidence in intravenous drug users.
Hepatitis C virus (HCV) genotypes are distributed differently depending on geography and route of infection. We characterized the distribution of genotypes in a large cohort of patients with chronic hepatitis C in the South-east of France and evaluated the relative prevalence according to time of acquisition. One thousand, one hundred-and-eighty-three patients who were anti-HCV-positive were studied. HCV genotype distribution has changed significantly from the 1960s to 2000. The prevalence of genotype 1b decreased from 47% before 1978 to 18.8% in the 1990s while the prevalence of genotype 1a and 3a increased during the same period from 18% and 15.3% to 28.8% and 26.3%, respectively. The logistic regression model showed that genotype 1a was significantly more common in patients infected through intravenous drug injection odds ratio ((OR): 2.08, P < 0.01) and after 1990 (OR: 1.98, P < 0.05). Genotype 1b was significantly less frequent in patients infected through intravenous drug injection (OR: 0.17, P < 0.001) and has decreased since 1978 (OR: 0.27, P < 0.001). Genotype 3a was independently associated with intravenous drug injection (OR: 6.1, P < 0.001) and tattooing (OR: 8.01, P < 0.001) and was more frequent in the 1979-90 period (OR: 2.05 and 1.74, P < 0.001 and P < 0.05). Our results show a modification of HCV genotypes distribution over the last four decades due to an increase of intravenous drug use (IVDU) contamination and an evolution of HCV genotypes distribution only in IVDU population characterized by a decrease of genotype 1b, an increase of genotype 3a from 1970 to 1990 and a higher increase of genotype 1a which is currently the predominant genotype in our population.
Adult↗
Analysis of habituated embryogenic lines in Asparagus officinalis L.: growth characteristics, hormone content and ploidy level of calli and regenerated plants.
Habituated asparagus embryogenic lines derived from eleven genotypes were maintained on hormone-free medium and grew actively through secondary embryogenesis. Secondary embryos were of single cell origin and emerged from the transversal division of some epidermal or subepidermal cotyledonary cells of primary embryos. The intensity of secondary embryogenesis was found to be variable between embryogenic lines. Plants regenerated from three of these lines have been previously demonstrated to carry a mutation whose phenotype was the direct appearance of somatic embryos on apices or nodes cultured on hormone-free medium. Habituated lines of embryogenic calli and various tissues of embryogenic mutant and wild type plants were analysed for their hormonal content in ABA, IAA, iP, Z and their metabolites ABA-GE, iPA, iMP, ZR. No significant difference was found between different embryogenic lines, except the level of iPA, or between cladophyll or apex cultures of mutant and wild type plants. Flow cytometry analyses indicated only 34% of the embryogenic lines were diploid, most of the others being tetraploid, but 62% of regenerated plants from these lines were diploid. This indicated the process of maturation and conversion selected diploid embryos in the embryogenic lines.
Journal Article↗
Direct transactivation of c-Ha-Ras gene by p53: evidence for its involvement in p53 transactivation activity and p53-mediated apoptosis.
p53 protein is a sequence-specific transcriptional activator which induces the expression of a number of cellular genes involved in different metabolic pathways. We report that the computer-selected sequence in human and mouse C-Ha-Ras gene confers to a reporter gene the ability to be directly transactivated by wild-type p53 either overexpressed or activated in response to a cellular stress. By analysing human transformed cell lines, we showed, at both mRNA and protein level, that the endogenous c-Ha-Ras gene expression is positively regulated by wt p53 protein. The stimulation of c-Ha-Ras gene expression in Saos-2Ts cells by a temperature shift down to the permissive temperature for the p53-wt conformation is associated with a significant increase in the activated form of p21c-Ha-Ras protein. Furthermore, in human transformed cell lines, the transient expression of a dominant interfering mutant of c-Ha-Ras greatly reduced the ability of p53 to induce apoptosis and inhibited the p53-dependent transactivation. This is due, at least in part, to a decrease in the protein (but not mRNA) level of the transiently expressed p53, indicating that inactivation of p21c-Ha-Ras signalling pathways led to a specific degradation of p53 protein. We therefore suggest that, by inducing c-Ha-Ras, p53 activates a positive feedback loop that counteracts the negative feedback loop mediated by Mdm2.
Animals↗
MOMP (major outer membrane protein) of Campylobacter jejuni; a versatile pore-forming protein.
The great majority of trimeric porins of Gram-negative bacteria cannot be dissociated into monomers without disrupting their folded conformation. The porin of Campylobacter jejuni, however, displays two folded structures, a classical oligomer and a monomer resistant to detergent denaturation. We probed the transition of trimer to monomer using light scattering experiments and examined the secondary structures of these two molecular states by infra-red spectroscopy. The channel-forming properties of both trimer and monomer were studied after incorporation into artificial lipid bilayers. In these conditions, the trimer induced ion channels with a conductance value of 1200 pS in 1 M NaCl. The pores showed marked cationic selectivity and sensitivity to low voltage. Analysis of the isolated monomer showed nearly the same single-channel conductance and the same selectivity and sensitivity to voltage. These results indicate that the folded monomer form of C. jejuni MOMP displays essentially the same pore-forming properties as the native trimer.
Antigens, Bacterial↗
Control of seed dormancy in Nicotiana plumbaginifolia: post-imbibition abscisic acid synthesis imposes dormancy maintenance.
The physiological characteristics of seed dormancy in Nicotiana plumbaginifolia Viv. are described. The level of seed dormancy is defined by the delay in seed germination (i.e the time required prior to germination) under favourable environmental conditions. A wild-type line shows a clear primary dormancy, which is suppressed by afterripening, whereas an abscisic acid (ABA)-deficient mutant shows a non-dormant phenotype. We have investigated the role of ABA and gibberellic acid (GA(3)) in the control of dormancy maintenance or breakage during imbibition in suitable conditions. It was found that fluridone, a carotenoid biosynthesis inhibitor, is almost as efficient as GA(3) in breaking dormancy. Dry dormant seeds contained more ABA than dry afterripened seeds and, during early imbibition, there was an accumulation of ABA in dormant seeds, but not in afterripened seeds. In addition, fluridone and exogenous GA(3) inhibited the accumulation of ABA in imbibed dormant seeds. This reveals an important role for ABA synthesis in dormancy maintenance in imbibed seeds.
Abscisic Acid↗
Covert transmission of hepatitis C virus during bloody fisticuffs.
Hepatitis C virus (HCV) is transmitted primarily through direct percutaneous exposure to infected blood. Sporadic HCV cases exist and may represent more than 10% of HCV transmission. We report the first case of documented transmission of HCV during a fight from a person who unknowingly had chronic HCV infection to a person who subsequently contracted acute hepatitis C. Patient-to-patient transmission was ascertained by sequence analysis of part of the NS5B genome and phylogenetic analysis. This case report suggests that sporadic HCV infection may be a result of blood exposure. This example of transmission could have a major impact in sports such as boxing or rugby. We suggest that in any fight, single use or nondisposable material should be used to dry blood to avoid such contamination.
Boxing↗
Characterization and molecular basis of the oligomeric structure of HIV-1 nef protein.
The Nef protein of human immunodeficiency virus type I (HIV-1) is an important determinant for the onset of AIDS disease. The self-association properties of HIV-1 Nef are analyzed by chemical cross-linking, dynamic light scattering, equilibrium analytical ultracentrifugation, and NMR spectroscopy. The experimental data show that the HIV-1 Nef core domain forms stable homo-dimers and trimers in solution, but not higher oligomers. These Nef homomers are not covalently linked by disulfide bridges, and the equilibrium between these forms is dependent on the Nef concentration. We further provide the molecular basis for the Nef core dimers and trimers obtained by analysis of crystallographic models. Oligomerization of biological polypeptides is a common tool used to trigger events in cellular signaling and endocytosis, both of which are targeted by Nef. The quaternary structure of Nef may be of physiological importance and may help to connect its cellular targets or to increase affinity of the viral molecule for its ligands. The herein described models for Nef dimers and trimers will allow further mutational studies to elucidate their role in vivo. These results provide novel insight into the structural and functional relationships of this important viral protein. Moreover, the oligomer interface may represent a novel target for the design of antiviral agents.
Biopolymers↗
[Lyell syndrome and Stevens-Johnson syndrome caused by lamotrigine].
BACKGROUND: Lamotrigine is a new anticonvulsant belonging to the triazine family. Several cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been described in patients taking this drug. We report 2 cases in children attending the same hospital. CASE REPORTS: Two children, aged 9 and 13 years, developed SJS and TEN respectively, 3 and 28 days after lamotrigine was added to their usual anticonvulsant regimen. In both cases, outcome was favorable despite major decline in psychomotor capacity in one. In the first case, chronological attributability was plausible for lamotrigine and doubtful for sodium valproate, clonazepam and hydrocortisone. In the second case, chronological attributability was probable for amoxicillin, plausible for lamotrigine and doubtful for sodium valproate, but the numerous previous absorptions of amoxicillin made lamotrigine more suspect. DISCUSSION: The risk of Steven-Johnson syndrome and toxic epidermal necrolysis is high with lamotrigine with an estimated frequency of 1/1000. This risk is probably higher than with other anticonvulsants. Associating lamotrigine with sodium valproate increases the frequency of adverse skin reactions.
Adolescent↗
Assessment of spontaneous fluctuations of viral load in untreated patients with chronic hepatitis C by two standardized quantitation methods: branched DNA and Amplicor Monitor.
Quantitation of hepatitis C virus (HCV) RNA in serum has been used to predict and monitor the efficacy of interferon therapy in chronic HCV infection. We prospectively studied the fluctuation of viremia by a longitudinal follow-up of HCV RNA levels for 2 months in six untreated patients. Spontaneous fluctuations of HCV RNA ranged from 2.8- to 5.7-fold with branched DNA assay and from 2.9- to 5.6-fold with Monitor. These large spontaneous fluctuations (up to 0.75 log), observed daily, weekly, and monthly, raise doubt about the clinical value of a single assessment of pretherapeutic viremia.
Adult↗
Novel double mutant CF allele identified in a cystic fibrosis patient with meconium ileus.
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Alleles↗
HIV-1 Nef protein: purification, crystallizations, and preliminary X-ray diffraction studies.
Human immunodeficiency virus Nef protein accelerates virulent progression of AIDS by its interaction with specific cellular proteins involved in cellular activation and signal transduction. Here we report the purification and crystallization of the conserved core of HIV-1LAI Nef protein in the unliganded form and in complex with the wild-type SH3 domain of the P59fyn protein-tyrosine kinase. One-dimensional NMR experiments show that full-length protein and truncated fragment corresponding to the product of HIV-1 protease cleavage have a well-folded compact tertiary structure. The ligand-free HIV-1 Nefcore protein forms cubic crystals belonging to space group P23 with unit cell dimensions of a = b = c = 86.4 A. The Nef-Fyn SH3 cocrystals belong to the space group P6(1)22 or its enantiomorph, P6(5)22, with unit cell dimensions of a = b = 108.2 A and c = 223.7 A. Both crystal forms diffract to a resolution limit of 3.0 A resolution using synchrotron radiation, and are thus suitable for X-ray structure determination.
Crystallization↗
Crystallization of monoacylated proteins: influence of acyl chain length.
The crystallization of monoacylated proteins has been investigated using a model system. Acylated derivatives of bovine pancreatic ribonuclease A, differing in their acyl chain lengths (10 to 16 carbon atoms), have been prepared using reverse micelles as microreactors. With one fatty acid moiety per polypeptide chain, covalently attached to the NH2 terminus of the protein, all the modified proteins have similar enzymatic activity and hydrodynamic radius as the native protein. Only the caprylated derivative can give crystals which diffract to high resolution. The resolved structure indicates that: (i) the protein folding is not modified by the chemical modification, (ii) the capryl moiety is not buried within the molecule but available for external interactions. Dynamic light scattering experiments on concentrated solutions show that the protein-protein interactions are dependent on acyl chain length. Proteins with the longest attached chains (14 and 16 carbon atoms) tend to self-associate through acyl group interactions.
Acylation↗
[Sarcoidosis with hematologic involvement and hypogammaglobulinemia].
BACKGROUND: Hematological changes are uncommon in childhood sarcoidosis. CASE REPORT: Case 1. This patient developed severe hemolytic anemia associated with splenomegaly at the age of 11 months. A second episode of hemolysis was seen at the age of 6 years; it was associated with thrombocytopenia and hypogammaglobulinemia. A partial splenectomy permitted histological diagnosis of sarcoidosis that was confirmed by elevated angiotensin-converting enzyme level, and subsequently developement of pulmonary involvement. Case 2. This boy suffered from autoimmune hemolytic anemia and thrombocytopenia associated with splenomegaly at the age of 3 years. At the age of 7 years, he had splenomegaly, enlarged cervical and lomboaortic lymph nodes and hypogammaglobulinemia. Diagnosis of sarcoidosis was made from lymph nodes and spleen biopsies after splenectomy; the patient had increased angiotensin-converting enzyme concentration, and subsequently developed specific renal involvement. CONCLUSION: Association of hemolytic anemia, thrombocytopenia, hypogammaglobulinemia and splenomegaly should suggest the diagnosis of sarcoidosis and could be considered as part of the disease spectrum.
Agammaglobulinemia↗
Evidence for a dimeric intermediate on the crystallization pathway of ribonuclease A.
Early steps in the crystallization process of pancreatic ribonuclease have been investigated by time-dependent fluorescence anisotropy, using a labeled protein as a fluorescent probe. Previous experiments have shown that steady-state fluorescence anisotropy is sensitive to protein-protein interactions and can be used to find new crystallization conditions. The present work describes an attempt, by means of time-resolved experiments, to detect and characterize species appearing in the early stages of the crystallization pathway. Fluorescence anisotropy decay was measured with synchrotron radiation as a light source under a variety of conditions where it is known that the solutions tend towards crystallization; the decay was analyzed by a maximum-entropy method that calculates a rotational correlation-time distribution. Fluorescence anisotropy originates in the Brownian rotatory motion of macromolecules and the values of the correlation times are related to the size and shape of different species present in the solution. In the presence of high salt concentrations, a bimodal distribution is always observed. Whereas a peak of protein monomer is still present, a second peak appears as a stable intermediate in the crystallization pathway. The correlation time of this new species varies between two and three times the correlation time of the monomer. The second peak is possibly the symmetrical dimer of the ribonuclease molecules commonly observed in all the high-salt crystal forms.
Journal Article↗
Identification of two loci involved in phytochrome expression in Nicotiana plumbaginifolia and lethality of the corresponding double mutant.
Four Nicotiana plumbaginifolia mutants exhibiting long hypocotyls and chlorotic cotyledons under white light, have been isolated from M2 seeds following mutagenesis with ethyl methane sulphonate. In each of these mutants, this partly etiolated in white light (pew) phenotype is due to a recessive nuclear mutation at a single locus. Complementation analysis indicates that three mutants, dap5, ems28 and ems3-6-34, belong to a single complementation group called pew1, while dap1 defines the pew2 locus. The mutants at pew1 contain normal levels of immunochemically detectable apoprotein of the phytochrome that is relatively abundant in etiolated seedlings, but are deficient in spectrophotometrically detectable phytochrome, whether seedlings are grown in darkness or light. Moreover, biliverdin, a precursor of the phytochrome chromophore, restores light-regulated responses in pew1 mutants and increases their level of photoreversible phytochrome when grown in darkness. These results indicate that the pew1 locus may be involved in chromophore biosynthesis. The mutant at the pew2 locus displays no photoreversible phytochrome in etiolated seedlings, but does contain normal levels of photoreversible phytochrome when grown in the light. Biliverdin had little effect on light-regulated responses in this mutant. In addition, biliverdin did not alter the level of phytochrome in etiolated seedlings. These observations lead us to propose that this mutant could be affected in the phyA gene itself. We have also obtained the homozygous double mutant at the pew1 and pew2 loci. This double mutant is lethal at an early stage of development, consistent with a critical role for phytochrome in early development of higher plants.
Biliverdine↗
Zea3: a pleiotropic mutation affecting cotyledon development, cytokinin resistance and carbon-nitrogen metabolism.
When photomorphogenesis takes place during early plant development, the cotyledons undergo a metabolic transition from heterotrophic sink metabolism to autotrophic source metabolism. A mutant screen was devised for seedlings affected in the regulation of nitrate assimilation during this early sink-source transition in Nicotiana plumbaginifolia. A mutant (EMS 203.6) was isolated for its inability to grow on low nitrate concentration. In contrast to wild-type (WT) plants, the mutant cotyledons remained tightly attached to each other throughout seedling development. It was found that a low carbon/nitrogen ratio (C/N ratio) in the medium was required for mutant growth. The higher the ratio was, the more the growth was inhibited. Mutant EMS 203.6 accumulated all amino acids in permissive conditions (low C/N ratio), and all amino acids and sugars also in selective (high C/N ratio) conditions. In addition, sucrose in the medium repressed light-regulated genes involved in nitrate assimilation and in photosynthesis in the mutant but not in the WT plants. The mutation was mapped to the Zea3 complementation group which confers resistance to zeatin. This zeatin resistance was associated with a hypertrophy of mutant cotyledons in response to cytokinin. Both cytokinin resistance and sensitivity to a high C/N ratio were not observed in etiolated mutant seedlings and were restricted to the jointed-cotyledon developmental stage. Previous physiological studies showed evidence for a role of cytokinins in the expression of nitrate reductase. Here, the first genetic evidence for a link between carbohydrate/nitrogen metabolism and cytokinin action during early development is provided.
Amino Acids↗
[Cytomegalovirus colitis in an immunocompetent patient].
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Aged↗