Effects of paliroden (SR57667B) and xaliproden on adult brain neurogenesis.
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Animals↗
Biomedical subjects
J Fournier
Publications and source records attributed to J Fournier.
Human cervical mucus can act in vitro as a selective barrier against spermatozoa carrying fragmented DNA and chromatin structural abnormalities.
PURPOSE: We have carried out experiments to determine if human cervical mucus can act as an in vitro selective barrier against spermatozoa morphologically normal that carry genetic structural abnormalities. METHODS: Sperm chromatin abnormalities have been evaluated by Chromomycin A3 and "endogenous" nick translation. RESULTS: The data obtained have shown that spermatozoa possessing higher levels of DNA protamination are more proficient in crossing the cervical mucus barrier. Moreover, the levels of positivity to endogenous nick translation treatment was practically zero in such spermatozoa. CONCLUSIONS: We suggest that sperm penetration of cervical mucus could be used to select sperm preparations free of fragmented DNA or chromatin structural abnormalities for assisted reproduction.
Cervix Mucus↗
Are children more accurate than adults? Spontaneous use of metaphor by children and adults.
This study examined an observation in which children outscored adults on a series of test questions, which included unusual items such as, "Do you see with your ears?" We assumed that the adults were treating the questions metaphorically because the literally correct answer was so obvious, an assumption consistent with Grice's theory. In Study 1, we tested this assumption by manipulating pretest and test items so as to suggest, or not suggest, a metaphorical or factual response. In Study 2, we used a similar manipulation involving the order of questions of various sorts and we more directly tested the Gricean hypothesis by giving college students a reason to treat the question literally. The results replicated the previous finding in which college students' scores were lower than those of children, and the condition effects suggested that the college students' performance was due to their responding metaphorically.
Adult↗
[Alcaloids discovery, markers for the history of organic chemistry].
The development of organic chemistry is well fitted by the history of dyes. Are alkaloids as good markers? In 1876, Chevreul distinguished two steps in the history of these organic alkalis. The first began with Derosne who analyzed opium in 1803, followed by Seguin and mainly Sertuerner. It was closed about 1820 with Pelletier and Caventou researches, including works of Robiquet and Gomes from Lisbon. Next years, chemists investigated properties and chemical structures. With Pasteur, alkaloids participated to the emergence of stereochemistry, and with Claude Bernard, to the birth of a new science, physiology. Chevreul could not anticipate success of organic synthesis which blooms during the XXth century.
Chemistry, Organic↗
Genetic diversity of carbofuran-degrading soil bacteria.
The genetic diversity of 128 carbofuran-degrading bacteria was determined by ARDRA (amplified ribosomal DNA restriction analysis) of 16S rDNA and restriction fragment length polymorphism analysis of the 16S-23S rDNA spacer region (IGS) using five endonucleases. The isolates were distributed in 26 distinct ARDRA groups and 45 IGS types revealing a high level of microbial diversity confirmed by ARDRA clustering and sequencing of 16S rDNA. The occurrence of a methylcarbamate-degrading gene (mcd) was monitored by polymerase chain reaction amplification using specific primers. The mcd gene was detected only in 58 bacteria and there was no clear relationship between the presence of this gene and the phylogenetic position of the strain.
Journal Article↗
Effects of hydroxyl radicals on outwardly rectifying chloride channels in a cultured human bronchial cell line (16HBE14o-).
Respiratory pathologies can result from the exposure of airway epithelial cells to oxidative stress. We studied the effects of the hydroxyl radical *OH, for which there is no natural intra- or extracellular scavenger, on an outwardly rectifying chloride channel (ORCC). In the human bronchial cell line 16HBE14o-, the cytoplasmic side of ORCC in inside-out excised membrane patches was exposed to *OH created by simultaneously superfusing Fe2+ and H2O2 in front of the patch-pipette. ORCC was activated by depolarizing voltage steps. Its open probability (Po) increased with bath [Ca2+] above 1 microM. Upon brief exposure to *OH, ORCC first closed and then alternated between periods of closure and normal activity. The duration of closure increased with the duration of *OH exposure but voltage steps could reopen the channel. After 10 min exposure to *OH, however, the channel closed irreversibly, regardless of the number of subsequent voltage steps or the duration of washing. Low [Ca2+] in the bath accelerated the irreversible closure of the channel in the presence of *OH. Intracellular application of *OH progressively inhibited ORCC activity by inducing long closure periods that increased with time. This might have important pathophysiological implications in the process of inflammation.
Bronchi↗
Preparation and pharmacological profile of 2-trifluoromethyl-benzo(8,9)-1,3-diaza-spiro (4,6)-undeca-2,8-diene and its enantiomers as new anti-obesity agents.
Obesity affects a large population of industrialised countries in which occurrence may reach 20%. The multifactorial aspect of the pathology prompted us to develop new entities associating favourable effects on both eating behaviour and metabolic parameters. The 2-trifluoromethyl-benzocyloheptene moiety has been combined with an imidazoline ring for synthesising a new anti-obesity agent. Preparation of the already known 2-trifluoromethyl-5-H-6,7,8,9-tetrahydro-benzocyclohepten-7-one as a key intermediate has been significantly improved, and an enantioselective procedure has been developed for imidazoline construction. The syntheses and pharmacological profiles of the compounds are presented here, particularly the effects on eating behaviour and body weight, and the putative involvement of the L-enantiomer in the treatment of metabolic diseases.
Animals↗
Effect of the neuroprotective compound SR57746A on nerve growth factor synthesis in cultured astrocytes from neonatal rat cortex.
The neurotrophic factor promoting activity of the neuroprotective compound SR57746A was evaluated in primary cultures of neonatal rat cortical astrocytes by studying the synthesis of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). A concentration- and time-dependent increase of nerve growth factor mRNA was induced by SR57746A (10 nM-1 microM). In these astrocytes, BDNF mRNA contents were increased to a significant but smaller extent, and beta-actin mRNA showed no variation. SR57746A (1 microM) induced increases of both de novo protein translation after 6 h of incubation and NGF release into the extracellular medium after 6-24 h. These effects were preceded by a transient augmentation of junB, c-fos and c-jun mRNA contents. These increases of AP-1 family mRNA were associated with increased nuclear AP-1 binding activity. The results show that SR57746A can increase the synthesis and release of NGF in rat cortical astrocytes. Such effects may contribute to the drug's previously described neuroprotective effects.
Animals↗
[Was Louis-Joseph Proust (1754-1826) a pharmacist?].
Proust's first formulation of the law of definite proportions was published in a paper on iron oxides (1794). He spent the major part of his professional life in Spain, where he contracted to take a teaching and searching position. He was apprenticed to his father to study pharmacy, and he studied chemistry with Hilaire-Marin Rouelle. His early interrupted education is shown through his abilities as an analyst, the persons with whom he was in communication, his share in manufacturers' assays and his researches towards health and food chemistry. More fundamental was his belief in natural principles of order as representative of the thought of the ideologues.
Chemistry↗
[Grape sugar manufacture assays under Premier Empire].
The Continental Blockade was established by the Decree of Berlin (1806). Scientists, manufacturers, and politicians were interested in grape sugar as a substitute for cane sugar. Grape sugar had been extracted and refined by Proust (1754-1826), in Spain, on a laboratory scale. He was invited by the Government to search a way of producing grape sugar on an industrial scale. As a scientist, he accompanied manufacturers in their assays. The matter is closed about 1811. It throws light on aspects of scientist's relationship, and part of authorities in the birth and failure of an agricultural industry. It signs the transition from an economic system directed by the Government to a system managed by manufactuers. This story forcasts the partition between scientists and manufacturers which will increase in France during all the century. As his compatriot Volney, Proust was an ideologue, searching for basic, general laws and useful science.
Food Supply↗
Tissue distribution and cellular localization of the levocabastine-sensitive neurotensin receptor mRNA in adult rat brain.
The aim of this study was to determine the regional and cellular distribution of the neurotensin type 2 receptor (NT-2R) mRNA in the rat brain. Using a radioactive in situ hybridization approach, the distribution of NT-2R transcripts was quantified from autoradiograms, and the cellular localization was examined in liquid emulsions. In rat brain, NT-2R mRNAs, are more widespread than the neurotensin type 1 receptor mRNA. NT-2R transcripts are diffusely distributed throughout the brain, with higher quantities found in the pia mater, the ventricles, the subfornical organ, the subiculum, the substantia nigra, the ventral tegmental area, the superior colliculus, the periaqueductal gray matter, the Purkinje cells and certain hypothalamic and brainstem nuclei. At the cellular level, silver grains appear to be concentrated on glia, neurons and ependymal cells, such as cell bodies of the glia-rich corpus callosum, Purkinje neurons in the cerebellum and ependymal cells lining the ventricles. In contrast, the thalamus and the amygdala contain low amounts of NT-2R mRNA. We discuss the anatomical location of NT-2R mRNA in relation to possible roles for this new receptor subtype.
Animals↗
The incompatible interaction between Phytophthora parasitica var. nicotianae race 0 and tobacco is suppressed in transgenic plants expressing antisense lipoxygenase sequences.
Nicotiana tabacum 46-8 cultivar displays an incompatible interaction with race 0 of Phytophthora parasitica var. nicotianae (Ppn), a fungal pathogen of most tobacco cultivars. At the plant level, incompatibility is characterized by the induction of lipoxygenase (LOX, EC = 1.13.11.12) activity and localized hypersensitive cell death before defense gene activation. To evaluate the involvement of LOX in the onset of plant defense, tobacco 46-8 plants were genetically engineered using full-length or partial-length antisense (AS) tobacco LOX cDNA constructs. AS expression strongly reduced elicitor- and pathogen-induced LOX activity. Eight independent AS-LOX lines were selected and assayed for their response to Ppn. After root or stem inoculation with race 0, all AS-LOX lines but one displayed a compatible phenotype whereas control transformed plants, not containing the AS-LOX cassette, showed the typical incompatible reaction. The presence of the fungus in transgenic lines was demonstrated by PCR amplification of a Ppn-specific genomic sequence. A linear relationship was found between the extent of LOX suppression and the size of the lesion caused by the fungus. The AS-LOX plants also showed enhanced susceptibility toward the compatible fungus Rhizoctonia solani. The results demonstrate the strong involvement of LOX in the establishment of incompatibility in plant-microorganism interactions, consistent with its role in the defense of host plants.
Journal Article↗
Improved differential screening approach to analyse transcriptional variations in organized cDNA libraries.
A cDNA library was generated from rat brain tissues and organized into 1536-well plates, using a fluorescence activated cell sorter (FACS), acting as a single cell deposition system. The organized library containing 10,000 clones, with 60% full-length cDNA inserts, allowed the generation of multiple identical membrane replicas. Each replica was hybridized with a complex probe obtained from a particular brain tissue or a given cultured cell. The signal intensity for each of the clones present on the membrane, quantified with a standard image-analysis software, is proportional both to the abundance of the corresponding mRNA in the probe and to the amount of plasmid template on the membrane. The latter value was thus used to normalize the signals produced with complex probes, to optimize the comparison of mRNA expression levels for the different systems under study. The construction of high-quality cDNA libraries, the generation of identical membrane replicas and comparable probes, and the utilization of an image-analysis software package, coupled with the normalization of the spot intensity by assaying plasmid quantity, significantly improves the differential screening approach. Altogether, these technical improvements open the possibility to compare a great number of different probes and, in consequence, to accumulate biological information for each clone present in an organized cDNA library. The functional information obtained should complement data from DNA sequencing projects.
Animals↗
Buffering capacity of coal and its acid-soluble Fe2+ content: possible role in coal workers' pneumoconiosis.
Epidemiological studies have shown that the prevalence of coal workers' pneumoconiosis (CWP) differed remarkably between different coal mine regions despite comparable exposures to respirable dust. In the United States, CWP was found to be most common in Pennsylvania coal miners and least common in miners from Utah. The active component(s) responsible for the regional differences in CWP has not yet been identified. In the present study, we found that coals from Pennsylvania, compared with Utah coals, showed a much lower buffering capacity as determined by the amount of acid consumed in order to reach pH 4.5, which is the pH of the phagolysosomes of macrophages. Moreover, the coals from Pennsylvania released large amounts of Fe2+ in the acidified extract, whereas the coals from Utah released little Fe2+. Using electron spin resonance (ESR), we found that the coals from Pennsylvania, but not from Utah, were effective in oxidizing formate by a radical pathway. Two coals, one from Utah with high buffering capacity and low acid-soluble Fe2+ and the other from Pennsylvania with low buffering capacity and high acid-soluble Fe2+, were then selected for cell treatment. We found that human tracheal epithelial (HTE) cells treated with the coal from Pennsylvania (10 microg/cm2) showed a 36% increase in oxidant formation over the control as detected by dichlorofluorescein assay, whereas the coal from Utah had no effect. An electrophoretic mobility shift assay was used to test the binding affinity of nuclear proteins extracted from the coal-treated HTE cells to an oxidative stress-responsive transcription factor activator protein-1 (AP-1) element. The coal from Pennsylvania with high acid-soluble Fe2+ (1 microg/cm2) activated AP-1 to the same extent as 10 microM H2O2, while the coal from Utah without acid-soluble Fe2+ had no effect. These results support our hypothesis that the prevalence of CWP may be higher in coal workers exposed to coal with high acid-soluble Fe2+ and low buffering capacity than in workers exposed to coal with low acid-soluble Fe2+ and high buffering capacity.
Buffers↗
The effect of the nonpeptide neurotrophic compound SR 57746A on the progression of the disease state of the pmn mouse.
1. The progressive motor neuronopathy (pmn) mouse is an autosomal recessive mutant, in which the homozygotes suffer caudio-cranial degeneration of motor axons and die several weeks after birth. This strain provides the opportunity of testing potential therapeutic strategies for the treatment of motor neurone diseases such as amyotrophic lateral sclerosis. We have performed a study of the effects on the pmn mouse of SR 57746A, an orally-active, non-peptide compound which has been found to exhibit neurotrophic effects in vitro and in vivo. In order to treat the affected mice from birth, the mothers were administered 2.5 mg kg(-1). p.o., SR 57746A every two days until the weaning of the offspring (at day 20); then the offspring were given every two days a dose of 30 microg kg(-1), p.o., until their death. 2. Affected mice treated with SR 57746A had a lifespan 50% longer than that of the vehicle-treated mice (P=0.01). Compared to vehicle-treated pmn mice, SR 57746A improved the performance of the pmn mice in three different behavioural tasks. SR 57746A also maintained the amplitude of the motor evoked response of the gastrocnemius muscle, reduced the distal motor latency, and delayed the occurrence of the spontaneous denervation activity in this muscle. Histological studies indicated that at 20 days of age the mean surface areas of the fibres of the sciatic nerve were higher in SR 57746A-treated than in vehicle-treated mice. 3. At present, SR 57746A is the only orally active, nonpeptide compound known to be capable of delaying the progression of the motor neurone degeneration in pmn mice.
Animals↗
Sonographic evaluation of intervillous flow in early pregnancy: use of echo-enhancement agents.
The uteroplacental circulation of the cynomolgus monkey was examined in early pregnancy using a high-resolution ultrasound scanner. Intravenous injection of an echo-contrast agent, Albunex (sonicated albumin), was used to enhance the color Doppler images obtained. The flow of blood into and out of the intervillous compartment was readily assessed and quantified using pulsed and color Doppler. Flow within the intracotyledonary space was pulsatile and indicative of a low-resistance system. Flow within the decidual veins was non-pulsatile. The use of echo-contrast agents may assist in the determination of intervillous flow in human pregnancy at a correspondingly early stage.
Albumins↗
Germline BRCA1 mutations in patients from 84 families with breast and/or ovarian cancers in northern France.
The BRCA1 gene modification is responsible for an autosomal dominant syndrome of inherited early onset breast and/or ovarian cancer. This gene is estimated to account for almost half of inherited breast cancers and three quarters of inherited breast/ovarian cancers. This suggests that about 1 in every 500 women may carry the BRCA1 mutation. The BRCA1 was isolated by positional cloning in 1994. More than 100 different mutations have been found in the germline of affected individuals. Using systematic sequencing, we looked at BRCA1 germline mutations in 84 patients treated at the Centre Oscar Lambret for breast and/or ovarian cancer who belonged to high-risk families. We found 39 mutations: 22 true mutations inducing modifications of the BRCA1 protein (BRCA1+), six mutations with unknown consequences on the BRCA1 protein, and eleven mutations corresponding to polymorphisms that had been described previously. All the BRCA1+ cases had a HPG3 tumour. The median age of discovery and the receptor positivity percentage are lower in hereditary breast cancer than in the standard population of the breast cancers treated in our centre. Conversely, most of the BRCA1+ patients are without node involvement. This shows that BRCA1 mutations are not always related to parameters thought to indicate a bad prognosis.
Adult↗
The non-peptide neuroprotective agents SR 57746A interacts with neurotrophin 3 to induce differentiation in the PC12 cell-line.
SR 57746A (1-(2beta-naphthylethyl)-4-(3-trifluoromethylphenyl)-1,2,5,6 -tetrahydropyridine hydrochloride) is a neuroprotective compound which potentiates nerve-growth factor (NGF)-induced differentiation in PC12 cells. We have evaluated the interaction of SR 57746A with the other members of the neurotrophin family in this cell-line. In contrast with NGF, neurotrophin-3 did not increase the differentiation of PC12 cells. However, the association of SR 57746A with neurotrophin-3 significantly increased neurite outgrowth. No significant activity on neurite outgrowth was observed with brain-derived neurotrophic factor or neurotrophin-4, either alone or combined with SR 57746A. These results indicate that as well as potentiating the effect of NGF SR 57746A enables neurotrophin-3, which alone is inactive, to increase the differentiation of these cells.
Animals↗