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41.
G Koren D Demitrakoudis R Weksberg M Rieder N H Shear M Sonely B Shandling S P Spielberg 《Teratology》1989,40(2):157-162
We evaluated the causality of the association between intrauterine exposure to phenytoin and postnatal neuroblastoma using an in vitro lymphocyte toxicity assay for phenytoin-induced reactions in an unusual sibship. In addition, we investigated intrauterine phenytoin exposure in a case series of infants and children with neuroblastoma diagnosed over 17 years at our center. The response of lymphocytes from our index case with neuroblastoma exposed in utero to phenytoin was within the normal range, whereas the mother and a sibling with fetal hydantoin syndrome (FHS) exhibited an intermediate toxicity. None of the 188 cases of childhood neuroblastoma diagnosed between 1969 and 1988 had been exposed in utero to phenytoin, indicating that, statistically, the drug cannot be associated with neuroblastoma in more than two cases with this malignancy in our cohort, or in 1.5% of all cases of neuroblastoma. Although our data do not suggest an association between phenytoin in pregnancy and postnatal neuroblastoma, it is still possible that there is an increased risk for neuroblastoma in children with FHS. 相似文献
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We review issues of myriapod phylogeny, from the position of the Myriapoda amongst arthropods to the relationships of the orders of the classes Chilopoda and Diplopoda. The fossil record of each myriapod class is reviewed, with an emphasis on developments since 1997. We accept as working hypotheses that Myriapoda is monophyletic and belongs in Mandibulata, that the classes of Myriapoda are monophyletic, and that they are related as (Chilopoda (Symphyla (Diplopoda + Pauropoda))). The most pressing challenges to these hypotheses are some molecular and developmental evidence for an alliance between myriapods and chelicerates, and the attraction of symphylans to pauropods in some molecular analyses. While the phylogeny of the orders of Chilopoda appears settled, the relationships within Diplopoda remain unclear at several levels. Chilopoda and Diplopoda have a relatively sparse representation as fossils, and Symphyla and Pauropoda fossils are known only from Tertiary ambers. Fossils are difficult to place in trees based on living forms because many morphological characters are not very likely to be preserved in the fossils; as a consequence, most diplopod fossils have been placed in extinct higher taxa. Nevertheless, important information from diplopod fossils includes the first documented occurrence of air-breathing, and the first evidence for the use of a chemical defense. Stem-group myriapods are unknown, but evidence suggests the group must have arisen in the Early Cambrian, with a major period of cladogenesis in the Late Ordovician and early Silurian. Large terrestrial myriapods were on land at least by mid-Silurian. 相似文献
46.
Bong-Seop Lee Aruna K. Nalla Ilana R. Stock Talia C. Shear Keith L. Black John S. Yu 《Bioorganic & medicinal chemistry letters》2010,20(17):5262-5268
The purpose of this study was to prepare and characterize nanometer-sized prodrug (nanoprodrug) of camptothecin. The camptothecin prodrug was synthesized using tetraethylene glycol spacer linked via carbonate bond to camptothecin and via ester bond to α-lipoic acid. The nanoprodrug was prepared through the spontaneous emulsification mechanism using the mixture of camptothecin prodrug and α-tocopherol which served as a structural matrix. The nanoprodrug was activated readily by porcine liver esterase and, with a much slower rate, by hydrolytic degradation. Upon longterm storage, the α-lipoic acid moiety of the camptothecin prodrug gradually oxidized without loss of structural integrity and therapeutic efficacy. Interestingly, the hydrolytic activation was negligible before the oxidation, but was significantly accelerated after the oxidation of the α-lipoic acid moiety, suggesting an oxidative stimuli-responsive activation of the prodrug. The camptothecin nanoprodrug was found to possess significant inhibitory effect on the proliferation of U87-MG glioma cells with an IC50 of 20 nM. 相似文献
47.
The genus Trilasma Goodnight & Goodnight, 1942 is reinstated for Mexican ortholasmatines, and Cladolasma Suzuki, 1963 is reinstated for two species from Japan and Thailand, Cladolasma parvula Suzuki, comb. n. and Cladolasma angka (Schwendinger & Gruber), comb. n. Eight new species in the subfamily Ortholasmatinae Shear & Gruber, 1983 are described, as follows: Ortholasma colossussp. n. is from California, Trilasma tempestadosp. n., Trilasma hidalgosp. n., Trilasma trispinosumsp. n., Trilasma ranchonuevosp. n., Trilasma petersprouseisp. n. and Trilasma chipinquensis, sp. n. are from México, and Trilasma tropicumsp. n. from Honduras, the farthest south for a dyspnoan harvestman in the New World. A new distribution record for Martensolasma jocheni Shear 2006 is given. The recently described Upper Cretaceous amber fossil Halitherses grimaldii Giribet & Dunlop 2005 is not a member of the Ortholasmatinae, but is likely a troguloidean of an undiagnosed family. 相似文献
48.
Abstract Acropsopilio neozealandiae (Forster) is a tiny endemic New Zealand harvestman previously reported from seven localities. Extensive pitfall collecting in the southern half of the North Island and northern quarter of the South Island produced 70 individuals, from 42 locations, documenting its local distribution. The collection method is described fully, to assist future work. All specimens that could be confidently identified were female, so it seems likely that A. neozealandiae reproduces, at least within our study areas, by parthenogenesis—as do at least two of its congeners. Our specimens showed no obvious morphological variation over their range. 相似文献
49.
Christine R Keenan Josephine SL Mok Trudi Harris Yuxiu Xia Saad Salem Alastair G Stewart 《Respiratory research》2014,15(1):55
Background
We have previously shown that transforming growth factor-beta (TGF-beta) impairs glucocorticoid (GC) function in pulmonary epithelial cell-lines. However, the signalling cascade leading to this impairment is unknown. In the present study, we provide the first evidence that TGF-beta impairs GC action in differentiated primary air-liquid interface (ALI) human bronchial epithelial cells (HBECs). Using the BEAS-2B bronchial epithelial cell line, we also present a systematic examination of the known pathways activated by TGF-beta, in order to ascertain the molecular mechanism through which TGF-beta impairs epithelial GC action.Methods
GC transactivation was measured using a Glucocorticoid Response Element (GRE)–Secreted embryonic alkaline phosphatase (SEAP) reporter and measuring GC-inducible gene expression by qRT-PCR. GC transrepression was measured by examining GC regulation of pro-inflammatory mediators. TGF-beta signalling pathways were investigated using siRNA and small molecule kinase inhibitors. GRα level, phosphorylation and sub-cellular localisation were determined by western blotting, immunocytochemistry and localisation of GRα–Yellow Fluorescent Protein (YFP). Data are presented as the mean ± SEM for n independent experiments in cell lines, or for experiments on primary HBEC cells from n individual donors. All data were statistically analysed using GraphPad Prism 5.0 (Graphpad, San Diego, CA). In most cases, two-way analyses of variance (ANOVA) with Bonferroni post-hoc tests were used to analyse the data. In all cases, P <0.05 was considered to be statistically significant.Results
TGF-beta impaired Glucocorticoid Response Element (GRE) activation and the GC induction of several anti-inflammatory genes, but did not broadly impair the regulation of pro-inflammatory gene expression in A549 and BEAS-2B cell lines. TGF-beta-impairment of GC transactivation was also observed in differentiated primary HBECs. The TGF-beta receptor (ALK5) inhibitor SB431541 fully prevented the GC transactivation impairment in the BEAS-2B cell line. However, neither inhibitors of the known downstream non-canonical signalling pathways, nor knocking down Smad4 by siRNA prevented the TGF-beta impairment of GC activity.Conclusions
Our results indicate that TGF-beta profoundly impairs GC transactivation in bronchial epithelial cells through activating ALK5, but not through known non-canonical pathways, nor through Smad4-dependent signalling, suggesting that TGF-beta may impair GC action through a novel non-canonical signalling mechanism. 相似文献50.
In vitro evaluation of a toxic metabolite of sulfadiazine 总被引:7,自引:0,他引:7
We have demonstrated the in vitro production of a potentially toxic metabolite of sulfadiazine Human lymphocytes were incubated with sulfadiazine and a murine hepatic microsomal drug metabolizing system. Toxicity to cells was assessed by trypan blue dye exclusion. Covalent binding of labelled sulfadiazine to microsomes also was studied. Sulfadiazine toxicity to cells was dependent on microsomes and NADPH. Binding and toxicity were decreased when microsomes were boiled or cytochrome P-450 inhibited, and by the addition of N-acetylcysteine or glutathione. The data suggest the production of a toxic intermediate of oxidative metabolism of sulfadiazine which is detoxified by conjugation with glutathione. Covalent binding of such metabolites to cell macromolecules could lead to cell death and, by acting as haptens, to secondary hypersensitivity reactions. 相似文献