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1.
《Drug metabolism and pharmacokinetics》2019,34(5):308-316
LC-MS quantification of drug metabolites is sometimes impeded by the availability of internal standards that often requires customized synthesis and/or extensive purification. Although isotopically labeled internal standards are considered ideal for LC-MS/MS based quantification, de novo synthesis using costly isotope-enriched starting materials makes it impractical for early stage of drug discovery. Therefore, quick access to these isotope-enriched compounds without chemical derivatization and purification will greatly facilitate LC-MS/MS based quantification. Herein, we report a novel 18O-labeling technique using metabolizing enzyme carboxylesterase (CES) and its potential application in metabolites quantification study. Substrates of CES typically undergo a two-step oxygen exchange with H218O in the presence of the enzyme, generating singly- and doubly-18O-labeled carboxylic acids; however, unexpected hydrolytic behavior was observed for three of the test compounds – indomethacin, piperacillin and clopidogrel. These unusual observations led to the discovery of several novel hydrolytic mechanisms. Finally, when used as internal standard for LC-MS/MS based quantification, these in situ labeled compounds generated accurate quantitation comparable to the conventional standard curve method. The preliminary results suggest that this method has potential to eliminate laborious chemical synthesis of isotope-labeled internal standards for carboxylic acid-containing compounds, and can be developed to facilitate quantitative analysis in early-stage drug discovery. 相似文献
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目的:研究^18氟—氟化脱氧葡萄糖(^18F-FDG)在下咽部肿瘤诊断中的作用。方法:20例下咽部肿瘤患者均接受^18F-FDG检查及CT、全组内镜(食管、咽喉、气管镜)检查。结果:20例下咽部肿瘤患者^18F-FDG检查结果显示:2例阴性;18例肿瘤原发部位有同位素浓集,其中5例伴异位同位素浓集。对此5例患者进一步临床、病理检查证实:1例食管部占位,2例肺部病变,2例为良性改变。^18F-FDG检查结果显示的病变范围与CT、内镜检查相符。结论:^18F-FDG检查可以提高下咽部肿瘤、尤其是隐匿的并发肿瘤诊断的准确性,明确病变范围,为临床治疗提供依据;同时又是一个简单、易行的下咽部肿瘤的随访检查手段。 相似文献
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Ronald C. Reinsch MD 《American journal of obstetrics and gynecology》1997,176(6):1381-1383
OBJECTIVE: The purpose of the study was to determine the incidence of isolated choroid plexus cysts in association with trisomy 18 and other abnormalities.STUDY DESIGN: All patients from June 1992 through December 1995 were followed up after a screening ultrasonography. Any patient with a choroid plexus cyst was offered genetic counseling and an amniocentesis. Screening ultrasonographic examinations were performed on 16,059 patients, and 301 patients had a fetus with a choroid plexus cyst. One hundred thirty patients elected to have an amniocentesis. Patients were followed up to delivery.RESULTS: Two hundred sixty-three patients had an isolated choroid plexus cyst. Thirty-eight patients had a choroid plexus cyst associated with additional risk factors. Risk factors included advanced maternal age, additional ultrasonographic abnormalities, past obstetric history, or family history. No abnormalities were noted in the group with an isolated choroid plexus cyst. Four patients had an abnormality when the choroid plexus cyst was associated with an additional risk factor, including two patients with trisomy 18 and one with trisomy 21.CONCLUSION: An isolated choroid plexus cyst was not associated with a trisomy or other abnormalities in this study. When a choroid plexus cyst was associated with an additional risk factor, 10.5% of the patients had an abnormality. Amniocentesis is recommended when a choroid plexus cyst is found in association with additional risk factors. (Am J Obstet Gynecol 1997;176:1381-3.) 相似文献
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A. Merzak C. Parker S. Koochekpour G. V. Sherbet G. J. Pilkington 《Neuropathology and applied neurobiology》1994,20(6):614-619
Invasion of the reconstituted extracellular matrix composite, Matrigel, by eight human glioma–derived cell lines and human fetal brain cells was assessed in vitro using 8 um polycarbonate filters in a modified Boyden migration chamber. With the exception of one low grade glioma derived cell line, all lines studied proved to be invasive while normal fetal brain cells failed to invade. This invasive potential was independent of the histological grade of the tumour from which the cell lines originated. In addition, the expression of the metastasis–associated gene 18A2lmts1 as well as the tissue inhibitor of metalloproteinases–2 (TIMP–2) was analysed in each of the glioma–derived cell lines. The 18A2/mtsl was expressed in all the cells studied with the exception of fetal brain cells and the low grade non–invasive glioma derived IPRK–7 cell line. The 18A2/mtsl related genes coding for the S100 subfamily of calcium binding proteins were found to be differentially and overexpressed in invasive cell lines. TIMP–2 was expressed only in noninvasive cell lines. These results suggest that the 18A2/ mtsl and TIMP–2 genes could play an important role in the invasive behaviour of human glioma cells in vitro. . 相似文献
8.
S. Leskinen-Kallio 《Clinical physiology and functional imaging》1994,14(3):329-335
Summary. The particular advantages of positron emission tomography (PET) technique are that it has higher sensitivity, higher resolution, and a higher quality of image than that found in conventional nuclear medicine. The possibility of quantification and the wide range of useful tracers have raised expectations of this new method. To date, most of the human PET cancer studies have been performed with [18F]fluorodeoxyglucose (FDG) or [11CJmethionine. These are good imaging agents for tumours. However, more specific radiopharmaceuticals are required if other features of tumour metabolism are to be observed, f11Thymidine may prove to be a good tracer for quantitative measurements of tumour proliferation and [18F]misonidazole has been suggested for imaging of hypoxia. 相似文献
9.
Molecular identification of a small supernumerary marker chromosome by in situ hybridization: diagnosis of an isochromosome 18p with probe L1.84 总被引:1,自引:0,他引:1
A dysmorphic child was found by cytogenetic analysis to have an extra small marker chromosome. The marker chromosome was shown to possess a chromosome 18 centromere by in situ hybridization, and probably represents an isochromosome 18p. Centromere specific probes should be of value in identifying extra small marker chromosomes, and thereby provide better understanding of the clinical significance of these. 相似文献
10.
Gérald Vanzetto Marc Janier Daniel Fagret Luc Cinotti Xavier André-Fouet Michel Comet Jacques Machecourt 《European journal of nuclear medicine and molecular imaging》1997,24(2):170-178
The best test presently available to ascertain residual viability within an infarct-related area involves the use of fluorine-18
fluorodeoxyglucose (FDG) to detect the persistence of some cellular metabolism. Rest reinjection of thallium-201 is a less
accurate alternative but is easy to perform. Iodinated fatty acids, which are used with standard gamma cameras, are proposed
as markers of cellular metabolism. This study was performed to assess the value of 16-iodo-3-methyl-hexadecanoic acid (MIHA)
as a marker of the residual cellular metabolism by comparison with FDG in patients with a recent myocardial infarction, and
to evaluate its contribution compared with the201Tl stress-redistribution-reinjection technique. Stress-redistribution-reinjection201T1 imaging, rest MIHA imaging and glucoseloaded FDG imaging were performed in 22 patients with recent myocardial infarction.
Out of the 628 myocardial segments obtained from the left ventricular analysis, 400 were hypoperfused (relative uptake <0.75
of maximum uptake on stress201T1 imaging), 177 of which were severely hypoperfused (relative uptake <0.50). Receiver operating characteristic (ROC) curves
for predicting metabolic myocardial viability with FDG were derived from the results in respect of (a)201T1 activity during exercise, redistribution and reinjection and (b) MIHA up-take, using the two FDG thresholds most commonly
considered to define metabolic viability (0.50 and 0.60). Analysis of the 400 hypoperfused segments demonstrated that201T1 reinjection was the most accurate test in predicting the presence of myocardial viability (area under the ROI curves=0.85
and 0.86 at the 0.50 and 0.60 FDG thresholds, respectively;P<0.05 vs other tests). The global predictive values of MIHA and201T1 reinjection were, respectively, 0.87 and 0.89 at the 0.50 FDG threshold (NS), and 0.82 and 0.87 at the 0.60 FDG threshold
(NS). When only the 177 severely hypoperfused segments were considered,201T1 reinjection remained the most accurate test (accuracy 0.84 at the 0.50 FDG threshold and 0.82 at the 0.60 FDG threshold),
while the accuracy of MIHA decreased significantly (0.78 at the 0.50 FDG threshold and 0.73 at the 0.60 FDG threshold,P<0.05 vs201T1 reinjection). In all circumstances, MIHA was less specific than201T1 reinjection for the detection of metabolic viability. In conclusion, in patients with recent myocardial infarction, MIHA
accurately detects the persistence of metabolic viability, but is not superior to201T1. 相似文献