排序方式: 共有63条查询结果,搜索用时 31 毫秒
11.
J R Claude V N Huyen J M Warnet F Blanc 《Comptes rendus des séances de l'Académie des sciences. Série D, Sciences naturelles》1975,281(9):599-604
Wistar rats were fed, during 56 weeks, a diet containing 5 g/kg of Aramite. At the end of the treatment, all the surviving animals show, on anatomo-pathological examination, malignant proliferation of the hepatic tissue and, in certain cases, of biliary ducts. This compound, proposed in the past as acaricide in agriculture, can thus be considered as a model substance for induction of malignant liver tumors. 相似文献
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Clayton TA Lindon JC Cloarec O Antti H Charuel C Hanton G Provost JP Le Net JL Baker D Walley RJ Everett JR Nicholson JK 《Nature》2006,440(7087):1073-1077
There is a clear case for drug treatments to be selected according to the characteristics of an individual patient, in order to improve efficacy and reduce the number and severity of adverse drug reactions. However, such personalization of drug treatments requires the ability to predict how different individuals will respond to a particular drug/dose combination. After initial optimism, there is increasing recognition of the limitations of the pharmacogenomic approach, which does not take account of important environmental influences on drug absorption, distribution, metabolism and excretion. For instance, a major factor underlying inter-individual variation in drug effects is variation in metabolic phenotype, which is influenced not only by genotype but also by environmental factors such as nutritional status, the gut microbiota, age, disease and the co- or pre-administration of other drugs. Thus, although genetic variation is clearly important, it seems unlikely that personalized drug therapy will be enabled for a wide range of major diseases using genomic knowledge alone. Here we describe an alternative and conceptually new 'pharmaco-metabonomic' approach to personalizing drug treatment, which uses a combination of pre-dose metabolite profiling and chemometrics to model and predict the responses of individual subjects. We provide proof-of-principle for this new approach, which is sensitive to both genetic and environmental influences, with a study of paracetamol (acetaminophen) administered to rats. We show pre-dose prediction of an aspect of the urinary drug metabolite profile and an association between pre-dose urinary composition and the extent of liver damage sustained after paracetamol administration. 相似文献
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Nerve growth factor is a mitogen for cultured chromaffin cells 总被引:4,自引:0,他引:4
Nerve growth factor (NGF) is essential for the survival and differentiation of a number of neural crest derivatives, including sympathetic and sensory neurones. While early studies suggested that NGF might also have a mitogenic effect on these neurones, subsequent work has favoured the interpretation that NGF promotes cell survival or differentiation rather than proliferation. We have addressed the issue of a mitogenic effect of NGF using adrenal chromaffin cells, which are endocrine cells derived from the neural crest, and are closely related to sympathetic neurones. Adrenal chromaffin cells respond to NGF in vitro by expressing neuronal traits. We now report that NGF elicits a mitotic response in cultured chromaffin cells from young rats, and that this response is blocked by an antiserum to 2.5S NGF. The chromaffin cells that divided in response to NGF can subsequently become neuronal in the continued presence of NGF. 相似文献
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Aury JM Jaillon O Duret L Noel B Jubin C Porcel BM Ségurens B Daubin V Anthouard V Aiach N Arnaiz O Billaut A Beisson J Blanc I Bouhouche K Câmara F Duharcourt S Guigo R Gogendeau D Katinka M Keller AM Kissmehl R Klotz C Koll F Le Mouël A Lepère G Malinsky S Nowacki M Nowak JK Plattner H Poulain J Ruiz F Serrano V Zagulski M Dessen P Bétermier M Weissenbach J Scarpelli C Schächter V Sperling L Meyer E Cohen J Wincker P 《Nature》2006,444(7116):171-178
The duplication of entire genomes has long been recognized as having great potential for evolutionary novelties, but the mechanisms underlying their resolution through gene loss are poorly understood. Here we show that in the unicellular eukaryote Paramecium tetraurelia, a ciliate, most of the nearly 40,000 genes arose through at least three successive whole-genome duplications. Phylogenetic analysis indicates that the most recent duplication coincides with an explosion of speciation events that gave rise to the P. aurelia complex of 15 sibling species. We observed that gene loss occurs over a long timescale, not as an initial massive event. Genes from the same metabolic pathway or protein complex have common patterns of gene loss, and highly expressed genes are over-retained after all duplications. The conclusion of this analysis is that many genes are maintained after whole-genome duplication not because of functional innovation but because of gene dosage constraints. 相似文献
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Hereditary pancreatitis caused by triplication of the trypsinogen locus 总被引:12,自引:0,他引:12
Le Maréchal C Masson E Chen JM Morel F Ruszniewski P Levy P Férec C 《Nature genetics》2006,38(12):1372-1374
Hereditary pancreatitis has been reported to be caused by 'gain-of-function' missense mutations in the cationic trypsinogen gene (PRSS1). Here we report the triplication of a approximately 605-kb segment containing the PRSS1 gene on chromosome 7 in five families with hereditary pancreatitis. This triplication, which seems to result in a gain of trypsin through a gene dosage effect, represents a previously unknown molecular mechanism causing hereditary pancreatitis. 相似文献
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Claude Liébecq 《Cellular and molecular life sciences : CMLS》1948,4(2):56-59
Summary (1) Coupled oxidation by atmospheric oxygen of systems containing hæmoglobin and various reducing agents results in the successive formation of oxyhæm, oxohæm, and pseudohæm from the prosthetic group of hæmoglobin.(2) Of the verdoglobins, sulfhæmoglobin is analogous to oxohæm whereas choleglobin and pseudohæmoglobin are pseudohæms and apparently identical.(3) It is at present impossible to decide whether the green intermediate in the physiological formation of bilirubin is sulfhæmoglobin or pseudohæmoglobin.(4) Part of the bilirubin formed in the body is probably derived from catalase, hæmatin, myoglobin and the cytochromes.
Conférence principale, présentée à la Société suisse de biologie médicale lors de la 127me Assemblée générale de la Société helvétique des sciences naturelles à Genève, le 31 août 1947. 相似文献
Conférence principale, présentée à la Société suisse de biologie médicale lors de la 127me Assemblée générale de la Société helvétique des sciences naturelles à Genève, le 31 août 1947. 相似文献
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Another continental pool in the terrestrial silicon cycle 总被引:1,自引:0,他引:1
Silicon is the second most abundant element on Earth. It is an important nutrient for phytoplankton and is readily absorbed by terrestrial vegetation; it also assists the removal of carbon dioxide from the atmosphere through the weathering of silicates. But the continental cycle of silicon is not well known, and only a few studies have attempted to use silicon stable isotopes (28Si, 29Si and 30Si) to quantify the continental silicon reservoirs. Dissolved silicon in sea and river waters forms a reservoir of mean isotopic value +1.1 per thousand (refs 7, 10). It is enriched in 30Si with respect to the igneous rocks reservoir, which has a mean isotopic value of -0.3 per thousand (refs 4, 9). This enrichment can only be produced by a major fractionation during weathering, and should result in the formation of a continental 30Si-depleted reservoir. Such a reservoir, however, has not been identified to date. Here we analyse silicon isotopes of in situ quartz from a sandstone series in France, using a new-generation secondary ion mass spectrometry apparatus. We show that quartz that precipitates as siliceous cements forms a strongly 30Si-depleted reservoir with isotopic values down to -5.7 per thousand, a more negative value than any previously published for terrestrial samples. Our findings suggest that quartz re-precipitation plays an important role in the biogeochemical cycle of silicon. 相似文献
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BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain 总被引:1,自引:0,他引:1
Coull JA Beggs S Boudreau D Boivin D Tsuda M Inoue K Gravel C Salter MW De Koninck Y 《Nature》2005,438(7070):1017-1021
Neuropathic pain that occurs after peripheral nerve injury depends on the hyperexcitability of neurons in the dorsal horn of the spinal cord. Spinal microglia stimulated by ATP contribute to tactile allodynia, a highly debilitating symptom of pain induced by nerve injury. Signalling between microglia and neurons is therefore an essential link in neuropathic pain transmission, but how this signalling occurs is unknown. Here we show that ATP-stimulated microglia cause a depolarizing shift in the anion reversal potential (E(anion)) in spinal lamina I neurons. This shift inverts the polarity of currents activated by GABA (gamma-amino butyric acid), as has been shown to occur after peripheral nerve injury. Applying brain-derived neurotrophic factor (BDNF) mimics the alteration in E(anion). Blocking signalling between BDNF and the receptor TrkB reverses the allodynia and the E(anion) shift that follows both nerve injury and administration of ATP-stimulated microglia. ATP stimulation evokes the release of BDNF from microglia. Preventing BDNF release from microglia by pretreating them with interfering RNA directed against BDNF before ATP stimulation also inhibits the effects of these cells on the withdrawal threshold and E(anion). Our results show that ATP-stimulated microglia signal to lamina I neurons, causing a collapse of their transmembrane anion gradient, and that BDNF is a crucial signalling molecule between microglia and neurons. Blocking this microglia-neuron signalling pathway may represent a therapeutic strategy for treating neuropathic pain. 相似文献
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