Biomedical subjects
Publications and source records attributed to E Renault.
In this paper a theoretical model is presented, which is based on a pass to pass analysis of the localized interaction between a short laser pulse with a wider electron distribution. It can be applied to a large class of physical phenomena and, in particular, to the case of a storage-ring free-electron laser (FEL). Numerical results are confirmed by experimental measurements done on the ACO and Super-ACO FELs.
Methylation of cytosine in the 5 position of the pyrimidine ring is a major modification of the DNA in most organisms. In eukaryotes, the distribution and number of 5-methylcytosines (5mC) along the DNA is heritable but can also change with the developmental state of the cell and as a response to modifications of the environment. While DNA methylation probably has a number of functions, scientific interest has recently focused on the gene silencing effect methylation can have in eukaryotic cells. In particular, the discovery of changes in the methylation level during cancer development has increased the interest in this field. In the past, a vast amount of data has been generated with different levels of resolution ranging from 5mC content of total DNA to the methylation status of single nucleotides. We present here a database for DNA methylation data that attempts to unify these results in a common resource. The database is accessible via WWW (http://www.methdb.de). It stores information about the origin of the investigated sample and the experimental procedure, and contains the DNA methylation data. Query masks allow for searching for 5mC content, species, tissue, gene, sex, phenotype, sequence ID and DNA type. The output lists all available information including the relative gene expression level. DNA methylation patterns and methylation profiles are shown both as a graphical representation and as G/A/T/C/5mC-sequences or tables with sequence positions and methylation levels, respectively.
Partial copper depletion of a variant rat hepatoma cell line induces a transient inhibition of growth and the genesis of stable, well-differentiated revertants. We report a burst of cell death, synchronous with the peak of reversion. The characteristics of this cell mortality were typical of apoptosis and included detachment from the plastic support, chromatin condensation and fragmentation, and internucleosomal DNA degradation. Although commitment to cell death was induced by copper deficiency, the apoptotic process was partially inhibited as assessed from electrophoretic patterns of DNA degradation. Redifferentiation was closely linked to the apoptotic death program. Analysis of rescued detached cells in all three media (standard, Cu-, Fe-) indicated that the frequency of revertants was significantly higher among floating as opposed to adherent cell populations. Nevertheless, experimental copper depletion increased by 10(4) times the revertant frequency among adherent cells. We propose that redifferentiation of the variant hepatoma cells (and concomitant recovery of tumorigenicity) is determined by the gene expression pattern of programmed cell death.
The antitumor drug pazelliptine (PZE) binds to natural and synthetic DNA sequences at 100 mM NaCl, pH 7.0, as deduced from the absorption and fluorescence data. Scatchard plots constructed from the results obtained with poly(dG-dC)-poly(dG-dC) give binding constants of base pairs in the range (2-6) x 10(5)M(-1). The modifications in the absorption and fluorescence spectra observed when PZE binds to various polynucleotides, namely poly(dA-dT)-poly(dA-dT), poly(dA)-poly(dT), poly(dG-dC)-poly(dG-dC) and calf thymus DNA, reveal a change in the protonation state of the drug upon binding, increasing the apparent pKa of its 9-N-nitrogen atom. The PZE excited state properties serve as a sensitive probe to distinguish between homo and hetero A-T sites as well as between AT and GC sites. Fluorescence studies reveal that energy transfer occurs from polynucleotide bases to the bound PZE chromophore, a result consistent with an intercalative mode of binding of the drug to DNA. The emission is enhanced when PZE is bound to A-T base pairs (approximately 30% increase of phi(F) whereas it is quenched in the vicinity of G-C base pairs (approximately 90% decrease of phi(F)). Furthermore, the fluorescence spectrum obtained with calf thymus DNA is hardly distinguishable from that obtained with poly(dG-dC)-poly(dG-dC), suggesting a binding of PZE to G-C rich regions.
Copper deficiency imposed on a variant rat hepatoma cell line inhibits cell growth and results in genesis of stable well-differentiated, tumorigenic revertants. The treatment caused a substantial increase in DNA content (up to 20%) of G1 and G2/M cells and inhibition of cell proliferation. This phenomenon was correlated with an enhancement of DNA replication. The excess DNA was unstable and rapidly lost with reinitiation of cell growth and mitosis. Minute and double-minute extrachromosomal material was detected by metaphase analysis, suggesting widespread DNA amplification in copper-deficient conditions. Although transitory, these genetic events were associated with genesis of drug-resistant cells and induction of tumorigenicity of the variant hepatoma cells. The data reveal a novel aspect of the consequences of trace element deficiency.
BACKGROUND: Myositis ossificans circumscripta is a benign lesion with an acute course and may simulate a malignant tumor. It usually follows trauma to soft tissue. CASE REPORTS: Case n. 1. A 13 year-old girl was admitted because of a painful inflammatory tumour in the left thigh. Initial X-rays were normal. Ultrasound imaging showed a heterogeneous echogenic mass with several extending shadow cones in the distal part of the vastus medialis muscle resembling a calcifying hematoma. Twenty days later, X-rays showed a vague calcified peripheral rim in the medial distal part of the thigh. White blood count was normal, and blood sedimentation rate was 46 millimeters in the first hour. CT scan showed a transparent zone between the lesion and the adjacent bone and a lucent central area, surrounded by a dense outer area consistent with myositis ossificans. Histological examination of the excised mass confirmed myositis ossificans. Two years later, the patient was asymptomatic and X-rays showed no ossification. Case n. 2. A 14 year-old girl suffered from pain in the right anterior hip area since 10 days. She denied any trauma. A firm mass was palpable in the anterior superior iliac spine area and X-rays revealed a calcific density. CT scan showed a dense bony mass in the right gluteus medius muscle clearly separated from the adjacent bony pelvis by a soft tissue plane. Histological examination of the excised mass confirmed myositis ossificans. One year later, the patient was asymptomatic and X-rays of the pelvis showed no ossification. CONCLUSION: Myositis ossificans circumscripta is rare in children. CT scan suggests the benign nature of the lesion by demonstrating integrity of bony cortex and characteristic disposition of calcifications. The biopsy is not necessary if the diagnosis is certain. Surgery permits to reduce the evolution.
Cells of a dedifferentiated rat hepatoma clone were submitted in vitro to copper deficiency. This treatment caused inhibition of cell growth. In addition, in treated cultures, the frequency of differentiated revertants selected in glucose-free medium was drastically increased when compared with the spontaneous frequency. The maximum effect was observed when cell proliferation spontaneously resumed after 20 days of copper deficiency. Furthermore, a copper depletion/replenishment protocol applied before the selection of revertants reduced the period of time of copper deficiency that was necessary to provoke the reversion process. It has been previously demonstrated that cell growth arrest and reinitiation may induce gene amplification events. Amplification of the dihydrofolate reductase gene as an indicator of such events was tested during the copper deficiency treatment. The frequency of cells resistant to increasing methotrexate concentrations due to gene amplification was enhanced by the treatment, just as was the frequency of differentiated revertants. These results suggest that in rat hepatoma cells the phenotypic transition to the stable differentiated state involves gene amplification and/or genome rearrangement.
The effect of 2 ns pulses of 355 nm laser light on aqueous solutions of pazelliptine (PZE) was investigated and biphotonic ionization was observed. The absorption spectrum corresponding to the pazelliptine radical cation (PZE+) and the hydrated electron simultaneously formed in this process was determined. In the absence of oxygen, eaq- reacted with unexcited PZE (k = 1.6 x 10(10) M-1 s-1) to give the pazelliptine radical anion (PZE-). This latter species was identified by separate pulse radiolysis experiments. The radicals cation and anion disappeared by recombination on the millisecond time range. In presence of oxygen, eaq- was scavenged by O2 leading to the formation of the superoxide radical (O2.-) in competition to the formation of the radical PZE.-.PZE+ reacted with O2.- to produce H2O2 (k = 9 x 10(9) M-1 s-1). The spectral analysis revealed that PZE triplet was also formed during the laser pulse. In the absence of oxygen, the triplet-triplet absorption decreased on the microsecond time scale (2k = 1.5 x 10(10) M-1 s-1). In oxygenated solutions, eaq- and the pazelliptine triplet decayed exponentially in the same time range.