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51.
Phase-locking neurons in the electrosensory lateral line lobe (ELL) of a weakly electric fish, Gymnarchus niloticus, fire an action potential in response to each cycle of the sinusoidal electrosensory signal (350-500 Hz) created by the fish's own electric organ. The exact firing times of the phase-locking neurons are altered (time-shifted) by capacitance of electrolocation objects or by electric organ discharges of other individuals. The magnitude of the time shifts depends on the location of the neurons' receptive field on the skin; thus, time disparities arise between the firing of phase-locking neurons. To compute these disparities, there should be a site where these phase-locking neurons converge. In this study we morphologically identified a novel cell type, which we named the "ovoidal cell", that receives the convergent projections of phase-locking neurons in the inner cell layer (ICL) of the ELL. We labeled these neurons with biocytin and examined them by light and electron microscopy. The giant cells and the S-type primary afferents, two types of phase-locking neurons, respectively terminate on the soma via chemical synapses and on the dendrite of the ovoidal cells via mixed synapses. Each terminal of the giant cells embraces the soma of an ovoidal cell, covering as much as 84% of the somatic membrane. The giant cell terminals and ovoidal cell somata were immunoreactive to SV2, a synaptic vesicle protein, but the S-afferent terminals were not, even though they contain numerous synaptic vesicles. The dendrite of the ovoidal cells also contacts the pyramidal cells of the ICL, which are known to be sensitive to time disparities. The anatomical connections of the phase-locking neurons to the ovoidal cells strongly suggest that they are involved in computing time disparity. 相似文献
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A clonal human skeletal muscle cell line showing acid maltase deficiency (AMD) was established through the transfection of origin-defective SV40 DNA. The low acid alpha-glucosidase activity and glycogenosomes in this clone corresponded to AMD. This clone, in spite of loading glycogenososmes, was competent not only as to proliferation without contact inhibition but also as to myogenic differentiation to some extent. Dexamethasone promoted the formation by the transformant of multinucleated myotubes, which expressed acetylcholine receptors. The existence of glycogenosomes did not seem to affect the proliferation or differentiation of myoblasts. The aberrant acid alpha-glucosidase expressed in the transformed myogenic clone was shown to be biochemically identical to that in AMD fibroblasts. This transformant should be of great value for investigating the pathogenesis of AMD because of the possibility of supplying semi-permanently a uniform myogenic cell line expressing AMD. 相似文献
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An improved understanding of mechanisms that underlie drug-induced liver injury (DILI) is required to enable design of drugs that have minimal potential to cause this adverse reaction in man. Available evidence suggests DILI arises in susceptible patients because of an imbalance between chemical insults (which are an inherent property of certain drugs and/or their metabolites) and the ability of the liver to mount compensatory/adaptive responses. In vivo safety testing in pre-clinical species ensures that drugs which enter clinical trials do not cause reproducible and dose-dependent liver injury in man, but is of limited value for exploration of underlying mechanisms and does not assess potential to cause rare idiosyncratic DILI. This review highlights the value that can be gained from in vitro studies using cultured hepatocytes and also hepatocyte-derived cell lines transfected with individual human cytochrome P450 (CYP450) isoforms. We have evaluated a range of mechanisms and endpoints (cell necrosis, mitochondrial injury, inhibition of biliary transporters and metabolite-mediated toxicity) using these model systems. Our data indicate that multiple mechanisms are likely to be involved in development of idiosyncratic DILI in man caused by numerous drugs, e.g. the anticonvulsant chlorpromazine. 相似文献
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M. LEMNAOUAR E. CHASTRE† A. PAUL M. MERGEY D. VEISSIÈRE G. CHERQUT P. BARBRY‡ B. SIMON-BOUY§ P. FANEN¶ C. GESPACH† J. PICARD 《European journal of clinical investigation》1993,23(3):151-160
Abstract. Primary tracheal epithelial cells obtained from two fetuses with cystic fibrosis (CF) were successfully transfected with a plasmid vector recombined with the large T oncogene of SV40. The resulting tracheal cells were propagated in culture for up to 25 passages and retained the mutations of the CF genes carried by the two fetuses, one heterozygous for the S549N and N1303K substitutions (CFT-I cells), and the other homozygous for the most common deletion ΔF508 (CFT-2 cells). The transfected cells: (a) expressed the SV40 large T oncogene, as determined by immunofluorescence and Northern blot analysis; (b) retained typical epithelial morphology, as assessed by the presence of microvilli, desmosomes, gap junctions, and cytokeratin expression; (c) were fully responsive to the cAMP-stimulating agents isproterenol, forskolin and vasoactive intestinal peptide for cAMP production and PKA activation; (d) do not produce any tumour in the athymic nude mice; (e) were diploid and tetraploid with a normal chromosomal complement at early passages, and (f) exhibited the abnormal regulation of chloride conductance characteristic of CF.
These results indicate that CFT-1 and CFT-2 cells constitute a suitable model for: (a) comparison of the maturation and function of the CFTR protein mutated in the two nucleotide-binding domains; (2) analysis of the biochemical defect in CF epithelial airway cells, (c) development of new therapeutic agents, and correction of the CF defect by gene replacement therapy in vitro . 相似文献
These results indicate that CFT-1 and CFT-2 cells constitute a suitable model for: (a) comparison of the maturation and function of the CFTR protein mutated in the two nucleotide-binding domains; (2) analysis of the biochemical defect in CF epithelial airway cells, (c) development of new therapeutic agents, and correction of the CF defect by gene replacement therapy in vitro . 相似文献
59.
目的:建立稳定遗传的纯合子SV40T胃壁细胞定位表达转基因小鼠品系。方法:通过定量PCR法比较已知杂合子小鼠和未知阳性小鼠中外源基因的起始模板量来确定小鼠的基因型,并通过测交的方法来验证试验结果。结果:用定量PCR法选育出15只纯合子小鼠,经测交验证它们与野生型小鼠交配所生的后代均为阳性,证明了定量PCR的结果是正确的。通过纯合子之间的全同胞交配建立了6个独立的纯合子品系。结论:定量PCR具有省时、省力及高通量等优点,能够很好地应用于筛选纯合子转基因动物。 相似文献
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The proteasome is the major cellular proteolytic machinery. It is involved in the regulation of various pathways via the selective degradation of either short-lived normal proteins or damaged proteins permitting the cellular detoxification. Proteasome has impaired function during several biological processes, including aging and diseases; however, it can be activated through overexpression of beta(5)- or beta(1)-subunits, resulting to enhanced survival and extended lifespan. In the current study, we have investigated proteasomal up-regulation via overexpression of hUMP1/POMP protein, the known accessory factor for proteasome assembly in humans. hUMP1/POMP overexpressing fibroblasts have increased levels of functional proteasome and enhanced capacity to cope better and faster with various oxidative stressors. These data highlight hUMP1/POMP role in proteasome assembly and further strengthen the prospect of genetic manipulation of the proteasomal system. 相似文献