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291.
Hilde MH Braakman Jan Lodder Alida A Postma Lambert FR Span Werner H Mess 《BMC neurology》2010,10(1):30
Background
The aetiology of central nervous system lesions observed in cerebral cyclosporine neurotoxicity remains controversial.Case presentation
We report a 48-year-old woman with a non-severe aplastic anaemia who presented with stroke-like episodes while on cyclosporine treatment.Transcranial Doppler ultrasound revealed severely elevated flow velocities in several cerebral vessels, consistent with vasospasm. Immediately after reducing the cyclosporine dose, the stroke-like episodes disappeared. Only after cyclosporine withdrawal the transcranial Doppler ultrasound abnormalities fully resolved.Conclusions
This case demonstrates a significant role of vasospasm in the pathway of cyclosporine-induced neurotoxicity. Transcranial Doppler ultrasound is an effective tool for the diagnosis and follow-up of cyclosporine-induced vasospasm.292.
293.
Dimitri Vanhecke Gudrun Herrmann Werner Graber Therese Hillmann-Marti Christian Mühlfeld Daniel Studer Matthias Ochs 《Histochemistry and cell biology》2010,134(4):319-326
Lamellar bodies are the storage sites for lung surfactant within type II alveolar epithelial cells. The structure–function models of lamellar bodies are based on microscopic analyses of chemically fixed tissue. Despite available alternative fixation methods that are less prone to artifacts, such as cryofixation by high-pressure freezing, the nature of the lung, being mostly air filled, makes it difficult to take advantage of these improved methods. In this paper, we propose a new approach and show for the first time the ultrastructure of intracellular lamellar bodies based on cryo-electron microscopy of vitreous sections in the range of nanometer resolution. Thus, unspoiled by chemical fixation, dehydration and contrasting agents, a close to native structure is revealed. Our approach uses perfluorocarbon to substitute the air in the alveoli. Lung tissue was subsequently high-pressure frozen, cryosectioned and observed in a cryo-electron microscope. The lamellar bodies clearly show a tight lamellar morphology. The periodicity of these lamellae was 7.3 nm. Lamellar bifurcations were observed in our cryosections. The technical approach described in this paper allows the examination of the native cellular ultrastructure of the surfactant system under near in vivo conditions, and therefore opens up prospectives for scrutinizing various theories of lamellar body biogenesis, exocytosis and recycling. 相似文献
294.
Bruno Studer Louise Bach Jensen Alice Fiil Torben Asp 《Molecular breeding : new strategies in plant improvement》2009,24(2):191-199
High resolution melting curve analysis (HRM) measures dissociation of double stranded DNA of a PCR product amplified in the
presence of a saturating fluorescence dye. Recently, HRM proved successful to genotype DNA sequence polymorphisms such as
SSRs and SNPs based on the shape of the melting curves. In this study, HRM was used for simultaneous screening and genotyping
of genic DNA sequence polymorphisms identified in the Lolium perenne F2 mapping population VrnA. Melting profiles of PCR products amplified from previously published gene loci and from a novel
gene putatively involved in vernalization response successfully discriminated genotypes in absence of allelic sequence information,
and allowed to determine allele segregation in VrnA. Here we introduce the concept of “blind” mapping based on HRM as a powerful,
fast and cheap method to map any DNA sequence polymorphisms without prior knowledge of allelic sequences in the key grassland
species perennial ryegrass (Lolium perenne L.). 相似文献
295.
The diverse family of alpha-crystallin-type small heat shock proteins (alpha-Hsps or sHsps) is characterised by a central, moderately conserved alpha-crystallin domain. Oligomerisation followed by dissociation of subparticles is thought to be a prerequisite for chaperone function. We demonstrate that HspH, a bacterial alpha-Hsp from the soybean-symbiont Bradyrhizobium japonicum, assembles into dynamic complexes freely exchanging subunits with homologous and heterologous complexes. The importance of the alpha-crystallin domain for oligomerisation and chaperone activity was tested by site-directed mutagenesis of 12 different residues. In contrast to mammalian alpha-Hsps, the majority of these mutations elicited severe structural and functional defects in HspH. The individual exchange of five amino acid residues throughout the alpha-crystallin domain was found to compromise oligomerisation to various degrees. Assembly defects resulting in complexes of reduced size correlated with greatly decreased or abolished chaperone activity, reinforcing that complete oligomerisation is required for functionality. Mutation of a highly conserved glycine (G114) at the C-terminal end of the alpha-crystallin domain specifically impaired chaperone activity without interfering with oligomerisation properties, indicating that this residue is critical for substrate interaction. The structural and functional importance of this and other residues is discussed in the context of a modeled three-dimensional structure of HspH. 相似文献
296.
Background
A beneficial effect of regional anesthesia on cancer related outcome in various solid tumors has been proposed. The data on prostate cancer is conflicting and reports on long-term cancer specific survival are lacking.Methods
In a retrospective, single-center study, outcomes of 148 consecutive patients with locally advanced prostate cancer pT3/4 who underwent retropubic radical prostatectomy (RRP) with general anesthesia combined with intra- and postoperative epidural analgesia (n=67) or with postoperative ketorolac-morphine analgesia (n=81) were reviewed. The median observation time was 14.00 years (range 10.87-17.75 yrs). Biochemical recurrence (BCR)-free, local and distant recurrence-free, cancer-specific, and overall survival were estimated using the Kaplan-Meier technique. Multivariate Cox proportional-hazards regression models were used to analyze clinicopathologic variables associated with disease progression and death.Results
The survival estimates for BCR-free, local and distant recurrence-free, cancer-specific survival and overall survival did not differ between the two groups (P=0.64, P=0.75, P=0.18, P=0.32 and P=0.07). For both groups, higher preoperative PSA (hazard ratio (HR) 1.02, 95% confidence interval (CI) 1.01-1.02, P<0.0001), increased specimen Gleason score (HR 1.24, 95% CI 1.06-1.46, P=0.007) and positive nodal status (HR 1.66, 95% CI 1.03-2.67, P=0.04) were associated with higher risk of BCR. Increased specimen Gleason score predicted death from prostate cancer (HR 2.46, 95% CI 1.65-3.68, P<0.0001).Conclusions
General anaesthesia combined with epidural analgesia did not reduce the risk of cancer progression or improve survival after RRP for prostate cancer in this group of patients at high risk for disease progression with a median observation time of 14.00 yrs. 相似文献297.
298.
A. terreus isolates isolated from some bakery products, corn and rice were found to be able to produce territrems. 90% of theA. terreus isolated from bakery products were able to produce territrem A, with a mean of 0.09 ppm, while 80% ofA. terreus isolates produce territrem B with a mean of 0.24 ppm. On the other hand 31.8% of the isolates ofA. terreus from corn were able to produce territrem A with a mean of 0.44 ppm. ConcerningA. terreus isolates from rice, 66.7% were found to produce territrem A, with a mean of 5.28 ppm, and 77.8% of the isolates produced
territrem B with a mean of 1.79 ppm. 相似文献
299.
Deoxycholic acid (DCA) causes ligand-independent activation of epidermal growth factor receptor (EGFR) and FAS receptor in primary hepatocytes: inhibition of EGFR/mitogen-activated protein kinase-signaling module enhances DCA-induced apoptosis 下载免费PDF全文
Qiao L Studer E Leach K McKinstry R Gupta S Decker R Kukreja R Valerie K Nagarkatti P El Deiry W Molkentin J Schmidt-Ullrich R Fisher PB Grant S Hylemon PB Dent P 《Molecular biology of the cell》2001,12(9):2629-2645
Previous studies have argued that enhanced activity of the epidermal growth factor receptor (EGFR) and the mitogen-activated protein kinase (MAPK) pathway can promote tumor cell survival in response to cytotoxic insults. In this study, we examined the impact of MAPK signaling on the survival of primary hepatocytes exposed to low concentrations of deoxycholic acid (DCA, 50 microM). Treatment of hepatocytes with DCA caused MAPK activation, which was dependent upon ligand independent activation of EGFR, and downstream signaling through Ras and PI(3) kinase. Neither inhibition of MAPK signaling alone by MEK1/2 inhibitors, nor exposure to DCA alone, enhanced basal hepatocyte apoptosis, whereas inhibition of DCA-induced MAPK activation caused approximately 25% apoptosis within 6 h. Similar data were also obtained when either dominant negative EGFR-CD533 or dominant negative Ras N17 were used to block MAPK activation. DCA-induced apoptosis correlated with sequential cleavage of procaspase 8, BID, procaspase 9, and procaspase 3. Inhibition of MAPK potentiated bile acid-induced apoptosis in hepatocytes with mutant FAS-ligand, but did not enhance in hepatocytes that were null for FAS receptor expression. These data argues that DCA is causing ligand independent activation of the FAS receptor to stimulate an apoptotic response, which is counteracted by enhanced ligand-independent EGFR/MAPK signaling. In agreement with FAS-mediated cell killing, inhibition of caspase function with the use of dominant negative Fas-associated protein with death domain, a caspase 8 inhibitor (Ile-Glu-Thr-Asp-p-nitroanilide [IETD]) or dominant negative procaspase 8 blocked the potentiation of bile acid-induced apoptosis. Inhibition of bile acid-induced MAPK signaling enhanced the cleavage of BID and release of cytochrome c from mitochondria, which were all blocked by IETD. Despite activation of caspase 8, expression of dominant negative procaspase 9 blocked procaspase 3 cleavage and the potentiation of DCA-induced apoptosis. Treatment of hepatocytes with DCA transiently increased expression of the caspase 8 inhibitor proteins c-FLIP-(S) and c-FLIP-(L) that were reduced by inhibition of MAPK or PI(3) kinase. Constitutive overexpression of c-FLIP-(s) abolished the potentiation of bile acid-induced apoptosis. Collectively, our data argue that loss of DCA-induced EGFR/Ras/MAPK pathway function potentiates DCA-stimulated FAS-induced hepatocyte cell death via a reduction in the expression of c-FLIP isoforms. 相似文献