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排序方式: 共有924条查询结果,搜索用时 31 毫秒
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Thomas Kretschmer Doan H. Nguyen Roger W. Beuerman Robert L. Tiel David G. Kline 《Journal of clinical neuroscience》2004,11(8):886-889
Ankyrin G has recently been shown to be responsible for activation of sodium channels in the developing and regenerating axonal membrane. Via this sodium channel mechanism, elevated ankyrin G levels have been linked with spontaneous ectopic hyperexcitability and thus with pain phenomena in nervous tissue. Ankyrin G, a transmembrane, structural protein of the axon, was examined in four conditions: (a) painful plexiform neurofibroma; (b) painful neuroma; (c) non-painful neuromas; (d) normal nerve. Neurofibroma tissue was obtained from an 18-year old male patient who developed an intensely painful, plexiform neurofibroma of the posterior femoral cutaneous nerve and subsequently underwent surgery. Sample proteins were separated by PAGE and labeled with anti-ankyrin G antibodies in a Western blot procedure. RESULTS: The ankyrin G band density (mug) of protein for the painful neurofibroma was 6014 and was 3557 for the painful neuroma as compared to 3041, 1988 and 606 (mean+/-SD=1878+/-1221) for the three non-painful neuromas. Ankyrin G expression in normal nerves (8 specimens from 7 patients) was comparatively less (mean+/-SD=411+/-339). CONCLUSION: Our results may represent the first evidence for abnormally increased levels of ankyrin G protein with painful neurofibromas. Due to ankyrin G's multifunctional role in the development and remodeling of excitable membranes, it can be hypothesized that the significant increase contributes to the development of hyperexcitable axonal membranes in neurofibromas and potentially other peripheral pain conditions. 相似文献
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J.E. Bailey-Wilson A.J.M. Sorant J.D. Malley S. Presciuttini R.A. Redner T.A. Severini J.A. Badner S. Pajevic R. Jufer A. Baffoe-Bonnie L. Kao B.Q. Doan J.L. Goldstein T.N. Holmes D. Behneman D.M. Mandal T.N. Turley K.A. Weissbecker J. O'Neill E.W. Pugh 《Genetic epidemiology》2001,21(Z1):S378-S383
A novel method for joint detection of association caused by linkage disequilibrium (LD) and estimation of both recombination fraction and linkage disequilibrium parameters was compared to several existing implementations of the transmission/disequilibrium test (TDT) and modifications of the TDT in the simulated genetic isolate data from Genetic Analysis Workshop 12. The first completely genotyped trio of affected child and parents was selected from each family in each replicate so that the TDT tests are valid tests of linkage and association, rather than being only valid as tests for linkage. In general, power to detect LD using the genome‐wide scan markers was inadequate in the individual replicate samples, but the power was better when analyzing several SNP markers in candidate gene 1. © 2001 Wiley‐Liss, Inc. 相似文献
95.
Anne‐Marie Sims Neil Shephard Kim Carter Tracy Doan Alison Dowling Emma L Duncan John Eisman Graeme Jones Geoffrey Nicholson Richard Prince Ego Seeman Gethin Thomas John A Wass Matthew A Brown MBBS MD FRACP 《Journal of bone and mineral research》2008,23(4):499-506
Using a moderate‐sized cohort selected with extreme BMD (n = 344; absolute value BMD, 1.5–4.0), significant association of several members of the Wnt signaling pathway with bone densitometry measures was shown. This confirms that extreme truncate selection is a powerful design for quantitative trait association studies of bone phenotypes. Introduction : Although the high heritability of BMD variation has long been established, few genes have been conclusively shown to affect the variation of BMD in the general population. Extreme truncate selection has been proposed as a more powerful alternative to unselected cohort designs in quantitative trait association studies. We sought to test these theoretical predictions in studies of the bone densitometry measures BMD, BMC, and femoral neck area, by investigating their association with members of the Wnt pathway, some of which have previously been shown to be associated with BMD in much larger cohorts, in a moderate‐sized extreme truncate selected cohort (absolute value BMD Z‐scores = 1.5–4.0; n = 344). Materials and Methods : Ninety‐six tag‐single nucleotide polymorphism (SNPs) lying in 13 Wnt signaling pathway genes were selected to tag common genetic variation (minor allele frequency [MAF] > 5% with an r2 > 0.8) within 5 kb of all exons of 13 Wnt signaling pathway genes. The genes studied included LRP1, LRP5, LRP6, Wnt3a, Wnt7b, Wnt10b, SFRP1, SFRP2, DKK1, DKK2, FZD7, WISP3, and SOST. Three hundred forty‐four cases with either high or low BMD were genotyped by Illumina Goldengate microarray SNP genotyping methods. Association was tested either by Cochrane‐Armitage test for dichotomous variables or by linear regression for quantitative traits. Results : Strong association was shown with LRP5, polymorphisms of which have previously been shown to influence total hip BMD (minimum p = 0.0006). In addition, polymorphisms of the Wnt antagonist, SFRP1, were significantly associated with BMD and BMC (minimum p = 0.00042). Previously reported associations of LRP1, LRP6, and SOST with BMD were confirmed. Two other Wnt pathway genes, Wnt3a and DKK2, also showed nominal association with BMD. Conclusions : This study shows that polymorphisms of multiple members of the Wnt pathway are associated with BMD variation. Furthermore, this study shows in a practical trial that study designs involving extreme truncate selection and moderate sample sizes can robustly identify genes of relevant effect sizes involved in BMD variation in the general population. This has implications for the design of future genome‐wide studies of quantitative bone phenotypes relevant to osteoporosis. 相似文献
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Sequence-specific binding and photocrosslinking of alpha and beta oligodeoxynucleotides to the major groove of DNA via triple-helix formation. 总被引:39,自引:15,他引:24 下载免费PDF全文
D Praseuth L Perrouault T Le Doan M Chassignol N Thuong C Hlne 《Proceedings of the National Academy of Sciences of the United States of America》1988,85(5):1349-1353
A photocrosslinking reagent (p-azidophenacyl) was covalently linked to an octathymidylate synthesized with either the natural (beta) anomer of thymidine or the synthetic (alpha) anomer. The oligothymidylate was further substituted by an acridine derivative to stabilize the hybrid formed with a complementary octadeoxyadenylate sequence via intercalation. A single-stranded 27-mer containing a (dA)8 sequence and a 27-mer duplex containing a (dA.dT)8 sequence were used as targets. Upon UV irradiation, photocrosslinking of the octathymidylate to its target sequence was observed, generating bands that migrated more slowly in denaturing gels. In the 27-mer duplex, both strands were photocrosslinked to the octathymidylate. Upon alkaline treatment of the irradiated samples, cleavage of the 27-mers was observed at specific sites. These reactions were analyzed at different salt concentrations. The location of the cleavage sites allowed us to demonstrate the following. (i) Both alpha and beta oligothymidylates can recognize a DNA double helix containing an oligo(dA).oligo(dT) sequence; the oligothymidylate binds to the major groove of DNA in a parallel orientation with respect to the adenine-containing strand of the DNA double helix. (ii) alpha oligothymidylates form helices with a complementary single-stranded oligodeoxyadenylate; the two strands have a parallel orientation independently of whether or not an intercalating agent is attached to the oligothymidylate. (iii) At low salt concentration, beta oligothymidylates form a double helix with an oligodeoxyadenylate in which, as expected, the two strands are antiparallel; at high salt concentration, a triple helix is formed in which the second oligothymidylate is oriented parallel to the adenine-containing strand. These results show that it is possible to recognize an oligopurine.oligopyrimidine sequence in a DNA double helix via local triple-helix formation and to target photochemical reactions to specific sequences in both double-stranded and single-stranded nucleic acids. 相似文献
99.
Although exostoses of the external auditory canal are not uncommon, those of the internal canal are extremely rare. One of these is described occurring in a 53-year-old man whose rapidly progressive hearing loss was without any associated abnormality. 相似文献
100.