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Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability 总被引:1,自引:15,他引:1
La Spada AR; Peterson KR; Meadows SA; McClain ME; Jeng G; Chmelar RS; Haugen HA; Chen K; Singer MJ; Moore D; Trask BJ; Fischbeck KH; Clegg CH; McKnight GS 《Human molecular genetics》1998,7(6):959-967
X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG
repeat expansion in the first exon of the androgen receptor (AR) gene.
Disease-associated alleles (37-66 CAGs) change in length when transmitted
from parents to offspring, with a significantly greater tendency to shift
size when inherited paternally. As transgenic mice carrying human AR cDNAs
with 45 and 66 CAG repeats do not display repeat instability, we attempted
to model trinucleotide repeat instability by generating transgenic mice
with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions
in their genomic context. Studies of independent lines of AR YAC transgenic
mice with CAG 45 alleles reveal intergenerational instability at an overall
rate of approximately 10%. We also find that the 45 CAG repeat tracts are
significantly more unstable with maternal transmission and as the
transmitting mother ages. Of all the CAG/CTG repeat transgenic mice
produced to date the AR YAC CAG 45 mice are unstable with the smallest
trinucleotide repeat mutations, suggesting that the length threshold for
repeat instability in the mouse may be lowered by including the appropriate
flanking human DNA sequences. By sequence-tagged site content analysis and
long range mapping we determined that one unstable transgenic line has
integrated an approximately 70 kb segment of the AR locus due to
fragmentation of the AR YAC. Identification of the cis - acting elements
that permit CAG tract instability and the trans -acting factors that
modulate repeat instability in the AR YAC CAG 45 mice may provide insights
into the molecular basis of trinucleotide repeat instability in humans.
相似文献
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In a child with some features of Turner's syndrome, gonosomal mosaicism with an isodicentric nonfluorescent (idic)Y chromosome was detected (mos 45,X/47,X,idic(Y)(q11),idic(Y)(11)/46,X,idic(Y)(q11)). Histopathological examination showed streak gonads with some evidence of ovarian stroma and no sign of gonadoblastoma. Polymerase chain reaction (PCR) analysis in blood lymphocytes and gonadal tissues using primers of seven loci along the Y chromosome, including the sex determined region (SRY), azoospermia factor region (AZF) and the deleted in azoospermia ( DAZ ) gene was positive for all loci tested, confirming the isodicentric character of the Y chromosome and indicating the presence of the AZF region. It is remarkable that the existence of spermatogenesis controlling genes does not play an important role in gonadal development and differentiation in a phenotypic female with some Turner stigmata. The data presented here are briefly discussed with previously-described patients. 相似文献
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F M Yatsu C Becker K R McLeroy B Coull J Feibel G Howard J F Toole M D Walker 《Stroke; a journal of cerebral circulation》1986,17(2):276-284
In order to assess the impact of variations in stroke care on outcomes, and to make geographic comparisons, the three Community Hospital-Based Stroke Programs in North Carolina, Oregon, and New York, aggregated their data on 4,132 hospitalized stroke patients. Complete demographic data or "Major Profile" were obtained on 2,390 (57.8%) of the 4,132 stroke patients. This includes those patients on whom informed patient and physician consents were obtained during the hospitalization. Of the major profile patients, 1,490 (62.3%) were followed for periods up to one year, 502 (21.0%) were lost to followup and 398 (16.6%) died within the one year followup period. Incomplete demographic data or "Minor Profile" were observed on 1,742 (42.1%) of the 4,132 patients. Minor profile includes those who died before comprehensive interviews were completed or those for whom informed consent for an interview could not be obtained. Of the minor profile group, 813 (46.7%) died in hospital, and 929 (53.3%) were alive when discharged from the hospital. This paper, which describes the programs, data collection procedures, and study cases, also highlights specific issues on stroke diagnosis, risk factors associated with stroke, and the influence of interventions on stroke outcomes. We conclude that: 1) the merging of data on hospitalized stroke cases from rural and urban hospitals in geographically distinct regions can be used in the study of stroke diagnosis, the use of diagnostic tests, and the effect of interventions on stroke outcomes; and 2) these data are consistent with the hypothesis that part of the national decline in mortality from stroke is due to a decline in stroke severity. 相似文献
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Renal transplant (RT) is now a therapy of choice for end stage renal disease (ESRD). The Nephrology Unit, Asvini started functioning in Dec 90 and to date 1298 sittings of hemodialysis have been given to 45 patients. Of these, 35 were in ESRD and 11 patients underwent renal transplantation at this hospital during the period Jan 91 – Dec 93. One patient expired after 18 months of transplantation due to infection. Early experience in screening patients for RT, use of immunosuppression, management of rejection episodes and protocol are presented with special emphasis on its relevance to the Armed Forces.KEY WORDS: Transplantation, Renal Failure, Immunosuppression, Rejection 相似文献
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McLeroy PA 《Hospital pharmacy》1994,29(10):939-40, 943
The Rule of 6 is a mathematical equation which can be used in crisis situations to accurately speed the calculation process when preparing a medication infusion. The following article discusses the origin of the Rule of 6, applications for its use and several examples. Also included is a compatibility chart for drugs the Rule of 6 is commonly used with and common IV fluids. Institution specific compounding techniques are also included. 相似文献
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PURPOSE. The purpose of this study was to determine the extent of implementation of school health education curricula, to identify factors which enhanced or impeded implementation, and to examine the link between the adoption and implementation phases of the diffusion process. DESIGN. The study used an experimental design; 22 school districts were randomly assigned to intervention and control conditions. SETTING. The study was conducted in North Carolina. SUBJECTS. All teachers in the study districts identified by their schools as "eligible to teach health" were included in the sample. INTERVENTION. An in-depth training was conducted on the use of the middle school tobacco prevention curriculum that had been adopted. MEASURES. Three measures were used to assess implementation of the curricula. Independent variables of interest included organizational size and climate, teacher training, how long it took to make the adoption decision, and attitudes toward tobacco use prevention curricula. Response rates for these measures ranged from 44% to 78%. RESULTS. Nonparametric correlations and regression modeling indicated that larger organizational size and teacher training were the strongest predictors of curricula implementation. A favorable organizational climate within school districts also improved implementation. CONCLUSIONS. While interventions to increase adoption of school health education curricula should focus on larger school districts, the majority of efforts to improve implementation should focus on smaller districts. 相似文献
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