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Ross BD; Jacobson S; Villamil F; Korula J; Kreis R; Ernst T; Shonk T; Moats RA 《Radiology》1994,193(2):457
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Candidate gene analysis in human neural tube defects 总被引:4,自引:0,他引:4
Boyles AL Hammock P Speer MC 《American journal of medical genetics. Part C, Seminars in medical genetics》2005,(1):9-23
Biochemical and developmental pathways, mouse models, and positional evidence have provided numerous candidate genes for the study of human neural tube defects. In a survey of 80 studies on 38 candidate genes, few found significant results in human populations through case-control or family-based association studies. While the folate pathway has been explored extensively, only the MTHFR 677C > T polymorphism was significant, and only in an Irish population. Developmental pathways such as the Wnt signaling pathway and Hox genes have also been explored without positive results. More than 90 mouse candidates have been identified through spontaneous and knockout mutations, but only the T locus (mouse Brachyury gene) showed association in an initial study that was not confirmed on follow-up. Positional candidates have been derived from cytogenetic evidence, but preliminary genomic screens have limited power due to small sample sizes. Future studies would increase their power to detect association by using more samples. In addition a clarification of the phenotype would be beneficial as many studies used different inclusion criteria. Incorporating several types of data could highlight better candidates, as would looking beyond the traditional sources for candidate genes. Recent studies of an energy metabolism gene (UCP2) and vitamin B metabolism (Transcoalbumin) have produced promising results. Utilizing other model organisms may also be beneficial, as in a recent study from a chick model of NTDs in NCAM1. New approaches combined with traditional methods and increased sample sizes will help prioritize human NTD candidate genes and clarify the complex etiology of this condition. 相似文献
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Huang Tien L. Székács András Uematsu Tamon Kuwano Eiichi Parkinson Andrew Hammock Bruce D. 《Pharmaceutical research》1993,10(5):639-648
Thirty carbonates, thiocarbonates, carbamates, and carboxylic esters of -naphthol, -naphthol, and p-nitrophenol were synthesized and tested as substrates for liver carboxylesterases from the crude microsomal fractions of human and mouse, and purified isozymes, hydrolases A and B, from rat liver microsomes. The carbonates, thiocarbonates, and carboxylic esters of -naphthol were cleaved more rapidly than the corresponding -naphthol isomers by the mammalian liver esterases. -Naphthyl esters of acetic, propionic, and butyric acids were among the best substrates tested for these enzymes. The majority of the substrates was consistently hydrolyzed at higher rates by hydrolase B compared with hydrolase A, although the Michaelis–Menten constant (K
m) values of selected substrates differed widely with these two isozymes. Malathion was a 15-fold better substrate for hydrolase B than for hydrolase A. Compared with the corresponding carboxylates, the carbonate moiety of - and -naphthol and p-nitrophenol lowered the specific activities of the enzymes by about fivefold but improved stability under basic conditions. The optimum pH of mouse liver esterase with the acetate, methylcarbonate, and ethylthiocarbonate of -naphthol was between pH 7.0 and pH 7.6. Human and mouse liver microsomal esterase activities were about five orders of magnitude lower than the esterase activities of purified rat liver hydrolase B. A relationship between the catalytic activity of the enzymes and the lipophilicity of the naphthyl substrates indicated that (i) in the - and -naphthyl carbonate series, an inverse relationship between enzyme activity and lipophilicity of the substrates was observed, whereas (ii) in the -naphthyl carboxylate series, an increase in enzyme activity with increasing lipophilicity of the substrates up to a log P value of about 4.0 was observed, after which the enzyme activity decreased. 相似文献
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Gill Sarjeet S.; Wie Siong I.; Guenthner Thomas M.; Oesch Franz; Hammock Bruce D. 《Carcinogenesis》1982,3(11):1307-1310
A rapid and sensitive indirect enzyme-linked immunosorbent assay(ELISA) was developed for micrsomal epoxide hydrolase of ratliver. The assay, which is easily and readily performed, issignificantly more sensitive than most enzymatic epoxide hydrolaseassays routinely used and electroimmunoassays previously developed.The limit of sensitivity of the ELISA is between 25 ngof microsomal epoxide hydrolase. Using the ELISA microsomalepoxide hydrolases of mouse and rat liver were shown to be antigenicallyvery similar, while microsomal epoxide hydrolases of guineapig, monkey and human liver are antigenically distinct fromthose of rat and mouse. The ELISA developed here is capableof detecting microsomal epoxide hydrolase of rat and mouse livereven when significant enzymatic activity is lost. These resultsindicate that the antigenic sites recognized by the antibodiesused are distinct from the catalytic site of the epoxide hydrolase.Approximately 1.9% of rat microsomal protein was quantifiedas microsomal epoxide hydrolase by the ELISA. Low levels ofmicrosomal epoxide hydrolase were also detected in rat livercytosol (0.02% of the cytosolic protein) demonstrating thatmicrosomal epoxide hydrolase is not totally membrane bound orthat an immunologically related protein occurs in the cytosolof normal rat liver. The ELISA developed here will be valuablein investigating further the role of microsomal epoxide hydrolase. 相似文献
8.
BD White A Kong E Khoo AM Southcott 《Journal of Medical Imaging and Radiation Oncology》2005,49(4):319-321
Tracheobronchopathia osteochondroplastica (TO) is a rare benign disease characterized by the presence of osseous and cartilaginous submucosal nodules projecting into the tracheobronchial tree. Most cases are asymptomatic and discovered incidentally at post‐mortem. We identified a case of TO on thoracic spiral CT and confirmed the diagnosis on bronchoscopy. This article reviews the imaging characteristics of TO, and shows the 3‐D virtual bronchoscopic and multiplanar reconstruction appearances of TO. 相似文献
9.
WBG Macdonald AP Patrikeos RI Thompson BD Adler AA Van Der Schaaf 《Journal of Medical Imaging and Radiation Oncology》2005,49(1):32-38
The present study compared the accuracy of ventilation perfusion scintigraphy (VQS) and CT pulmonary angiography (CTPA) for the diagnosis of pulmonary embolism. This was a prospective observational study of 112 patients with suspected pulmonary embolism (PE) who could be studied with both investigations within 24 h. Results were compared to final diagnosis at completion of 6-month follow up, using receiver operating characteristic (ROC) analysis. Pulmonary embolism was diagnosed in 27 referred patients (24%). The sensitivity and specificity of VQS and CTPA were similar to that reported from the literature. A normal VQ scan had the highest negative predictive value (100%), while a high-probability VQ scan had the highest positive predictive value (92%). There was no overall difference (area under the ROC curve (AUC)) between VQS (AUC (95% CI) = 0.82 (0.75,0.89)) and CTPA (AUC = 0.88 (0.81,0.94)) for the diagnosis of PE. Among patients with abnormal chest X-rays, CTPA (AUC 0.90 (0.83,0.97)) appeared somewhat better than VQS (AUC 0.78 (0.68,0.88)) but this difference did not reach statistical significance. In this instance, CTPA is at least as accurate as VQS and may provide an opportunity to make alternative diagnoses. 相似文献
10.
Shelley Brown DuTeaux John W Newman Christophe Morisseau Elise A Fairbairn Karen Jelks Bruce D Hammock Marion G Miller 《Toxicological sciences》2004,78(2):187-195
Epoxide hydrolases play an important role in detoxifying epoxides that arise from the metabolism of xenobiotic and endogenous compounds. Both the soluble and microsomal forms of epoxide hydrolase (sEH and mEH, respectively) have been detected in the rat testis. Because of the important role the epididymis plays in sperm maturation and protection, the present study evaluated the presence and activity of these two epoxide hydrolases in the rat epididymis. Using Western blotting, protein bands consistent in size with both mEH and sEH were detected in the caput, corpus, and cauda of the epididymis. The mEH immunoreactive bands in the epididymis ( approximately 50 kDa) were consistent with mEH detected in the liver and kidney. The sEH immunoreactive bands in the epididymis ( approximately 65 kDa) were consistent with a recombinant sEH standard and sEH detected in the liver, kidney, and testis. The presence of mEH and sEH in the epididymis was supported by observations from substrate-based enzyme assays. Results indicated that epididymal mEH can hydrolyze [(3)H]-cis-stilbene oxide to the corresponding diol at levels approximately 9% of the kidney. Epididymal sEH hydrolyzed the substrate [(3)H]-trans-diphenylpropene oxide to the corresponding diol and this activity was inhibited by cyclohexyl-dodecyl urea. Arachidonic acid epoxygenase activity was detected in epididymal S9 fractions, suggesting that fatty acid metabolism by epididymal cytochrome P450s can form epoxides that subsequently become substrates for epididymal sEH. Results from the present study indicate that the epididymis contains at least two active forms of epoxide hydrolase. The role of these enzymes in the detoxification of xenobiotic epoxides is well known, although it is unclear what cellular role they may play in the formation of biologically active metabolites in the epididymis. 相似文献