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排序方式: 共有539条查询结果,搜索用时 15 毫秒
161.
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Dramatic, expansion-biased, age-dependent, tissue-specific somatic mosaicism in a transgenic mouse model of triplet repeat instability 总被引:5,自引:0,他引:5
Fortune MT Vassilopoulos C Coolbaugh MI Siciliano MJ Monckton DG 《Human molecular genetics》2000,9(3):439-445
Myotonic dystrophy type 1 (DM1) is one of a growing number of inherited human diseases whose molecular basis has been implicated as the expansion of a trinucleotide DNA repeat. Expanded disease-associated alleles of >50 CTG repeats are unstable in both the germline and soma. Expansion of the unstable alleles over time and variation of the level of mutation between the somatic tissues of an individual are thought to account at least partially for the tissue specificity and progressive nature of the symptoms. We previously generated a number of transgenic mouse lines containing a large expanded CTG repeat tract that replicated a number of the features of unstable DNA in humans, including frequent sex-specific changes in allele length during intergenerational transmission. Small length change mutations were apparent in the somatic tissues of young mice in all of the lines generated, but the gross instability observed in human DM1 patients was not replicated. We now show that in one of the lines, Dmt -D, spectacular, expansion-biased, tissue-specific instability is observed in older mice. The highest levels of instability were detected in kidney with gains of >500 repeats, representing a tripling of allele length, in some cells. Mosaicism accumulated in an age-dependent manner, but the tissue specificity did not obviously correlate with cell turnover. Such gross somatic mosaicism was not observed in three other lines examined, further emphasizing a role for flanking DNA in modulating repeat stability. 相似文献
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Fortune JB Feustel P 《Archives of surgery (Chicago, Ill. : 1960)》2003,138(9):996-1000; discussion 1001
HYPOTHESIS: Large-bore subclavian intravenous access is important during trauma resuscitation and to provide central access in the intensive care unit. Controversy exists as to the patient position that best facilitates the insertion of this line. Duplex scanning of the subclavian vein in different body positions may help define which provides the largest vein size and distance from the clavicle. DESIGN: Prospective comparison study in healthy humans. SETTING: Clinical research laboratory. SUBJECTS: Ten healthy volunteers. INTERVENTIONS: We examined the left subclavian vein diameter, position from clavicle, and flow in subjects placed in 5 different positions advocated for subclavian vein puncture. A duplex scanner was used to image the subclavian vein with B-mode ultrasonography and to detect flow rates with a Doppler probe. The different subject positions were as follows: (1) flat (or supine), head and shoulders neutral; (2) flat, head neutral, shoulders arched; (3) flat, head opposite, shoulders arched; (4) Trendelenburg, head opposite, shoulders arched; and (5) Trendelenburg, head and shoulders neutral. RESULTS: The mean (SEM) diameter of the subclavian vein is largest in position 5 (0.99 [0.06] cm) and smallest in position 2 (0.84 [0.05] cm). The distance of the vein from the clavicle is greatest in position 1 (0.94 [0.08] cm) and least in position 4 (0.75 [0.07] cm). Using an analysis of variance with Dunnett's comparison, all positions were compared with position 5. For vein diameter, all positions had significantly smaller size. In position 4, the vein was significantly closer to the clavicle. There was no statistical difference in flow rates among all positions. CONCLUSIONS: These data demonstrate that arching of the shoulders and turning of the head may reduce target size and provide an unsatisfactory position for subclavian puncture. The Trendelenburg position with no other positioning maneuvers may be helpful. 相似文献
166.
We assessed the growth of the rat photopic electroretinogram (ERG) during light adaptation and the mechanisms underlying this process. Full field ERG responses were recorded from anesthetized adult Brown-Norway rats at each minute for 20 min of light adaptation (backgrounds: 1.8, 2.1, 2.4 log scotopic cd m(-2)). The rat photopic b-wave amplitude increased with duration of light adaptation and its width at 33% maximal amplitude narrowed (by approximately 40 ms). These effects peaked 12-15 min after background onset. The narrowing of the b-wave reflected steepening of the b-wave recovery phase, with little change in the rising phase. OP amplitudes grew in proportion to the b-wave. Inhibition of inner retinal responses using TTX resulted in a greater relative growth of b-wave and OP amplitude compared with fellow control eyes, and delayed the change in recovery phase by approximately 5 min. Inhibition of all ionotropic glutamate receptors with CNQX/D-AP7 delayed both rising and recovery phases equally (approximately 12 ms) without altering b-wave width or the time course of adaptation changes. These outcomes suggest that inner retinal light responses are not directly responsible for b-wave amplitude growth, but may contribute to the change in its recovery phase during adaptation. A TTX-sensitive mechanism may help to hasten this process. The cone a-wave was isolated using PDA/L-AP4 or CNQX/L-AP4. A-wave amplitude (35 ms after stimulus onset) also increased with time during light adaptation and reached a maximum (130 +/- 29% above baseline) 12-15 min after background onset. B-wave amplitude growth in fellow control eyes closely followed the course and relative magnitude of cone a-wave amplitude growth. Hence, the increase of the cone response during light adaptation is sufficient to explain b-wave amplitude growth. 相似文献
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J G Cannon C Suarez-Gutierrez T Lee J P Long B Costall D H Fortune R J Naylor 《Journal of medicinal chemistry》1979,22(4):341-347
A series of cis- and trans-dihydroxycotahydrobenzo[f]quinoline congeners of dopamine has been prepared, in which the N substitutent is H, ethyl, or n-propyl. The trans isomers include the dopamine moiety held rigidly in an antiperiplanar diposition which is believed to be necessary for certian central and peripheral dopaminergic effects. The cis isomers are flexible molecules; the dopamine moiety lacks conformational integrity and it can exist in a conformation which is believed not to favor dopaminergic activity. The trans series of compounds was shown to possess a high level of central and peripheral dopaminergic effects, whereas the cis series was of low activity or was inert. These data further support previous proposals concerning stereochemical requirements for certain dopaminergic agonist activity. 相似文献
170.
J G Cannon Z Perez J P Long D B Rusterholz J R Flynn B Costall D H Fortune R J Naylor 《Journal of medicinal chemistry》1979,22(8):901-907
A series of N-alkylated alpha-methyldopamine derivatives has been prepared for comparison of their biological effects with those of semirigid dopamine congeners derived from 2-aminotetralin systems. All of the alpha-methyldopamine derivatives were inert as dopaminergic agonists in a variety of animal assays, both centrally and peripherally, although certain compounds produced powerful and prolonged locomotor hyperactivity on intra-accumbens injection in mice, by indirect mechanism(s). A rationalization, based upon conformational analysis, is presented for the lack of direct dopaminergic agonist activity of alpha-methyldopamine derivatives. 相似文献