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1.
Determination of phospholipidosis potential based on gene expression analysis in HepG2 cells. 总被引:1,自引:0,他引:1
Franck Atienzar Helga Gerets Simon Dufrane Karen Tilmant Miranda Cornet Stephane Dhalluin Bernard Ruty Geoffrey Rose Michael Canning 《Toxicological sciences》2007,96(1):101-114
Phospholipidosis (PLD) is characterized by an intracellular accumulation of phospholipids in lysosomes and the concurrent development of concentric lamellar bodies. Recently, H. Sawada et al. (2005, Toxicol. Sci. 83, 282-292) identified 17 genes as potential biomarkers of PLD in HepG2 cells. The present study was undertaken to determine if this set of genes measured by quantitative PCR could be validated in the same cell line. The objective was also to investigate the dose-response relationship to further validate the assay and to select the concentrations to use for screening activities. In a first experiment (one concentration tested), out of the 17 genes, the best gene biomarkers of PLD (i.e., 11 genes) were selected for practical screening reasons. Based on these genes, 91.6% (i.e., 11 of 12) of the compounds known to induce PLD were identified as positive and all the negative compounds (i.e., five of five) were also confirmed. When the data obtained in the first experiment were compared to the data by Sawada et al., (2005) the coefficient of correlation calculated was slightly higher than 75%. In the second experiment (26 compounds [all 17 compounds from the first experiment plus 9 other compounds] tested at a minimum of three concentrations), 93.3% (14/15) of the compounds known to induce PLD were identified as such and all the negative controls (six compounds) were also confirmed. Three compounds likely to induce PLD were identified as positive in our assay. Finally, two compounds for which no data are available were also tested. When both experiments 1 and 2 were compared, the coefficient of correlation for 16 compounds tested at the same concentrations reached 87.7%. In conclusion, the present study further confirms the utility of gene expression in HepG2 cells to identify a potential to induce PLD. Finally, based on the data presented, researchers are encouraged to use a range of minimum three concentrations (e.g., 12.5, 25, and 50 microM) to screen for PLD in the human HepG2 cell line. 相似文献
2.
Peritoneal morphology in children treated by continuous ambulatory peritoneal dialysis 总被引:2,自引:0,他引:2
Fritz Schneble Klaus-Eugen Bonzel Rüdiger Waldherr Sebastian Bachmann Helga Roth Karl Schärer 《Pediatric nephrology (Berlin, Germany)》1992,6(6):542-546
Fifty peritoneal biopsies (PB) from 35 patients with end-stage renal disease, treated by continuous ambulatory peritoneal dialysis (CAPD) and aged 2 months to 18 years, were examined by light microscopy (n=50) and/or scanning electron microscopy. PB were performed during surgical procedures immediately before the start of, during, or after the cessation of CAPD treatment. PB from 15 children without renal disease undergoing laparatomy were examined similarly. Before the start of CAPD, a scarcity and shortening of the mesothelial microvilli was observed by scanning electron microscopy. During and after CAPD, variable alterations of mesothelium, interstitium and capillaries were found. The mesothelial layer was absent in all 5 PB obtained during episodes of active peritonitis. In patients treated by CAPD for longer than 6 months, mesothelial denudation was observed more frequently (6/11) than in children treated for shorter periods (1/7) (P<0.08). Fibrosis of the peritoneal membrane was present in about 50% of patients during or after the cessation of CAPD without impairment of peritoneal function. No correlation was found between the presence of fibrosis and the frequency of peritonitis or the duration of CAPD treatment. 相似文献
3.
4.
Helga Coulter 《British Journal of Psychotherapy》1991,7(3):251-259
SUMMARY. The relationship between mother and observer in mother-infant observation as described by Esther Bick is examined. Specifically, the question as to whether this relationship influences what is being observed is considered.
The author gives an account of her own relationship as an observer with a mother. The mother was an epileptic and fell with her baby (then six weeks old) causing the baby to suffer a broken skull. Exploration of events during the period of observation leads to the conclusion that the relationship between the mother and the observer was one of transference. Within this transference the observer seemed to be the mother of the one observed. This together with the effects on the observed mother's unconscious conflict with her own mother due to epilepsy is described.
Given transference in the mother-observer relationship doubts are raised as to the tenability of the attitude of distance and non-interference prescribed for the observer. The conclusion is drawn that, in any case, the role of the observer is a participant role, which poses the epistemological problem of the interference of the observer with the observed. 相似文献
The author gives an account of her own relationship as an observer with a mother. The mother was an epileptic and fell with her baby (then six weeks old) causing the baby to suffer a broken skull. Exploration of events during the period of observation leads to the conclusion that the relationship between the mother and the observer was one of transference. Within this transference the observer seemed to be the mother of the one observed. This together with the effects on the observed mother's unconscious conflict with her own mother due to epilepsy is described.
Given transference in the mother-observer relationship doubts are raised as to the tenability of the attitude of distance and non-interference prescribed for the observer. The conclusion is drawn that, in any case, the role of the observer is a participant role, which poses the epistemological problem of the interference of the observer with the observed. 相似文献
5.
6.
Hilmir Asgeirsson Finnbogi Jakobsson Haukur Hjaltason Helga Jonsdottir Sigurlaug Sveinbjornsdottir 《Movement disorders》2006,21(3):293-298
In Iceland, the crude prevalence for all types of primary dystonia was 37.1/10(5) (confidence interval, 30.4-44.9). Focal dystonia had the highest prevalence (31.2/10(5)), followed by segmental (3.1/10(5)), multifocal (2.4/10(5)) and generalized dystonia (0.3/10(5)). Cervical dystonia was the most common focal dystonia (11.5/10(5)), followed by limb dystonia (8.0/10(5)), laryngeal dystonia (5.9/10(5)), blepharospasm (3.1/10(5)), and oromandibular dystonia (2.8/10(5)). The male:female ratio for all patients was 1:1.9 (P=0.0007), and females outnumbered males in all subtypes except oromandibular dystonia. Mean age of onset for all patients was 42.7 years (range, 3-82 years). This prevalence of primary dystonia is higher than in most reported studies, possibly because of more complete ascertainment but the relative frequencies of dystonia subtypes is similar. 相似文献
7.
Derik Hermann Alexander Sartorius Helga Welzel Sigrid Walter Gisela Skopp Gabriele Ende Karl Mann 《Neuropsychopharmacology》2007,61(11):1281-1289
BACKGROUND: Cannabinoids present neurotoxic and neuroprotective properties in in vitro studies, inconsistent alterations in human neuroimaging studies, neuropsychological deficits, and an increased risk for psychotic episodes. METHODS: Proton magnetic resonance spectroscopy ((1)H-MRS), neuropsychological testing, and hair analysis for cannabinoids was performed in 13 male nontreatment-seeking recreational cannabis users and 13 male control subjects. RESULTS: A significantly diminished N-acetylaspartate/total creatine (NAA/tCr) ratio in the dorsolateral prefrontal cortex (DLPFC) was observed in cannabis users (p = .0003). The NAA/tCr in the putamen/globus pallidum region correlated significantly with cannabidiol (R(2) = .66, p = .004). Results of the Wisconsin Card Sorting test, Trail making Test, and D2 test for attention were influenced by cannabinoids. CONCLUSIONS: Chronic recreational cannabis use is associated with an indication of diminished neuronal and axonal integrity in the DLPFC in this study. As chronic cannabis use is a risk factor for psychosis, these results are interesting because diminished NAA/tCr ratios in the DLPFC and neuropsychological deficits were also reported in schizophrenia. The strong positive correlation of NAA/tCr and cannabidiol in the putamen/globus pallidum is in line with neuroprotective properties of cannabidiol, which were also observed in in vitro model studies of Parkinson's disease. 相似文献
8.
9.
A unique exonic splice enhancer mutation in a family with X-linked mental retardation and epilepsy points to a novel role of the renin receptor 总被引:6,自引:0,他引:6
Ramser J Abidi FE Burckle CA Lenski C Toriello H Wen G Lubs HA Engert S Stevenson RE Meindl A Schwartz CE Nguyen G 《Human molecular genetics》2005,14(8):1019-1027
The renin-angiotensin system (RAS) is essential for blood pressure control and water-electrolyte balance. Until the discovery of the renin receptor, renin was believed to be mainly a circulating enzyme with a unique function, the cleavage of angiotensinogen. We report a unique mutation in the renin receptor gene (ATP6AP2) present in patients with X-linked mental retardation and epilepsy (OMIM no. 300423), but absent in 1200 control X-chromosomes. A silent mutation (c.321C>T, p.D107D) residing in a putative exonic splicing enhancer site resulted in inefficient inclusion of exon 4 in 50% of renin receptor mRNA, as demonstrated by quantitative RT-PCR. Analysis of membrane associated-receptor molecular forms showed the presence of full-length and truncated proteins in the patient. Functional analysis demonstrated that the mutated receptor could bind renin and increase renin catalytic activity, similar to the wild-type receptor, but resulted in a modest and reproducible impairment of ERK1/2 activation. Thus, our findings confirm the importance of the RAS in cognitive processes and indicate a novel specific role for the renin receptor in cognitive functions and brain development. 相似文献
10.