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排序方式: 共有5212条查询结果,搜索用时 31 毫秒
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Theresa M. Thole Joern Toedling Annika Sprüssel Sebastian Pfeil Larissa Savelyeva David Capper Clemens Messerschmidt Dieter Beule Stefanie Groeneveld-Krentz Cornelia Eckert Guido Gambara Anton G. Henssen Sabine Finkler Johannes H. Schulte Anja Sieber Nils Bluethgen Christian R. A. Regenbrecht Annette Künkele Marco Lodrini Angelika Eggert Hedwig E. Deubzer 《International journal of cancer. Journal international du cancer》2020,146(4):1031-1041
Accurate modeling of intratumor heterogeneity presents a bottleneck against drug testing. Flexibility in a preclinical platform is also desirable to support assessment of different endpoints. We established the model system, OHC-NB1, from a bone marrow metastasis from a patient diagnosed with MYCN-amplified neuroblastoma and performed whole-exome sequencing on the source metastasis and the different models and passages during model development (monolayer cell line, 3D spheroid culture and subcutaneous xenograft tumors propagated in mice). OHC-NB1 harbors a MYCN amplification in double minutes, 1p deletion, 17q gain and diploid karyotype, which persisted in all models. A total of 80–540 single-nucleotide variants (SNVs) was detected in each sample, and comparisons between the source metastasis and models identified 34 of 80 somatic SNVs to be propagated in the models. Clonal reconstruction using the combined copy number and SNV data revealed marked clonal heterogeneity in the originating metastasis, with four clones being reflected in the model systems. The set of OHC-NB1 models represents 43% of somatic SNVs and 23% of the cellularity in the originating metastasis with varying clonal compositions, indicating that heterogeneity is partially preserved in our model system. 相似文献
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Sonographic evaluation of gallbladder kinetics: in vitro and in vivo comparison of different methods to assess gallbladder emptying. 总被引:3,自引:0,他引:3
Bernd Wedmann Gabriele Schmidt Martin Wegener Christoph Coenen Dieter Ricken Cornelia Drge 《Journal of clinical ultrasound : JCU》1991,19(6):341-349
In an in vitro study, 10 gallbladders of adult pigs and 6 gallbladders of lambs, all removed immediately after slaughtering, were stimulated in a water bath by electric means to induce active contraction. Gallbladder emptying was followed by ultrasonography employing five measurement procedures: (1) gallbladder width, (2) longitudinal planimetry, (3) transverse planimetry, (4) ellipsoid method, and (5) sum of cylinders method. In an in vivo investigation, gallbladder emptying of 30 volunteers (12 healthy subjects, 18 diabetics) was evaluated in the same way after ingestion of a fatty meal. Gallbladder width was found to be unsuitable to estimate the decrease in gallbladder volume due to a nonlinear relation of the parameters. Longitudinal planimetry tended to be less valid than transverse planimetry in assessing gallbladder volume reduction. The most valid estimation of gallbladder volume decreases was obtained by the two three-dimensional procedures. However, in neither in vitro nor in vivo could a significant difference between the sum of cylinders method and the ellipsoid method in determining relative volume reduction be established. We conclude that a three-dimensional measurement procedure should be used for valid assessments of gallbladder motility. However, according to our data there is no advantage in using the time-consuming sum of cylinders method compared to the simple ellipsoid method. 相似文献
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Jens J Bock Peter Maurer Cornelia Otto Robert A W Fuhrmann Johannes Schubert 《Journal of cranio-maxillo-facial surgery》2006,34(3):156-161
AIM: The aim of this study was to analyse possible intra- and postoperative complications and long-term results in combined orthodontic-orthognathic treatment of mentally handicapped patients compared with a control group of patients without handicap. PATIENTS AND METHODS: A group of 20 mentally handicapped patients (male = 7, female = 13) and of 102 non-handicapped patients (male = 36, female = 66) were evaluated retrospectively. The results of the two point-discrimination sensory test and the cephalometric findings of both groups were assessed. Complications during and after the operation, the results of nerve function tests and relapse rates were reported. The statistical analysis was carried out using binary logistical regression analysis with adjustment according to the diagnosis and the type of operation (p < 0.05) RESULTS: No significant differences could be found between the mentally handicapped and the non-handicapped patients. Only the nerve function test immediately postoperatively revealed differences between the two patient groups. The relapse rate in mentally handicapped patients was similar to non-handicapped patients. Forty-seven months after the operation, relapse (change in the ANB angle of more than 0.5 degrees ) was observed in four patients only (handicapped patients). CONCLUSION: Orthognathic surgical procedures in mentally handicapped patients can be carried out with a similarly high success rate as in mentally healthy patients. 相似文献
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Claudia Linde Cornelia Löffler Christina Kessler U. Quast 《Naunyn-Schmiedeberg's archives of pharmacology》1997,356(4):467-474
In vascular smooth muscle, openers of ATP-dependent potassium channels (K
ATP channels), such as P1075 (N-cyano-N’-(1,1-dimethylpropyl)-N’’-3-pyridylguanidine), produce relaxation. In this study we have investigated the effects of thiol-modifying agents on the
binding of P1075 and on the 86Rb+ efflux stimulating and vasorelaxant effects of the opener in rat aortic rings. The increase in 86Rb+ efflux induced by P1075 was taken as a qualitative measure of K+ channel opening. The hydrophilic SH-group-oxidizing substance, thimerosal (1 to 100μM), abolished specific binding of [3H]-P1075 with an IC50 value of 7.6±1.2μM; at 30μM, the half time for inhibition was 38min. Two other thiol-oxidizing agents, PMB (4-hydroxy-mercuribenzoic
acid) and DTBNP (2,2’-dithio-bis(5-nitropyridine)), inhibited binding up to 86% and 44%, respectively. The disulphide bond
reducing substance, DTT (1,4-dithiothreitol, 0.1 to 1mM), reduced [3H]-P1075 binding by up to 20% and partially reversed the inhibitory effect of thimerosal. In 86Rb+ efflux experiments, thimerosal (3 to 100μM) concentration-dependently increased basal efflux but inhibited P1075-stimulated
tracer efflux with an IC50 value of 7±1μM. The inhibitory effect occurred with a half-time of approximately 8min and was essentially reversed by DTT.
In rings precontracted with noradrenaline, thimerosal inhibited the vasorelaxant effect in a noncompetitive manner, shifting
the concentration-relaxation curves to the right and reducing maximum relaxation.The data show that oxidation of thiol groups
interferes with the binding of the K
ATP channel opener, P1075; concomitantly, the 86Rb+ efflux stimulating and the vasorelaxant effects are inhibited. Reduction of disulphide bonds by DTT has only minor effects
on the action of P1075. Collectively, the results suggest that intact thiol groups are essential for the functioning of the
KATP channel in rat aorta. The different kinetics governing the inhibition of opener binding and of opener-stimulated 86Rb+ efflux suggest that the SH-groups involved in the two processes differ in their accessibility to thimerosal and/or in their
reactivity.
Received: 7 April / Accepted: 9 July 1997 相似文献