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排序方式: 共有336条查询结果,搜索用时 15 毫秒
1.
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
2.
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
3.
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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Scavetta K Oh C Caldron R Abdel-Dayem T Al-Zaibag M Jutzy KR Marsa RJ Sjolander M Ribeiro PA 《Angiology》1999,50(11):891-899
The results and complications of a single-center experience of stent implantation in old saphenous vein grafts (SVGs) need to be defined. The authors studied their initial consecutive 92 patients (125 stents, 1.4 stents/per patient) with a mean age of 67+/-9 years. The patients' mean saphenous vein graft (SVG) age was 10+/-4 years, and the mean left ventricular ejection fraction was 46%+/-15. Patient population included unstable angina (65%), stable angina (10%), myocardial infarction (21%), and silent ischemia (4%). The authors implanted 122 Palmaz-Schatz/biliary and three Gianturco-Roubin stents. They aimed at a balloon-artery ratio of 1.1/1.0. Procedural success, defined as stent deployment with <50% stenosis without death/Q-wave myocardial infarction/coronary artery bypass grafting (MI/CABG) was 95%. The mean luminal diameter (MLD) increased from 0.6+/-0.5 to 3.3+/-0.8 mm (p<0.001) and mean SVG stenosis diameter was decreased from 80%+/-14 to -10%+/-11 (p<0.001). Angiographic SVG lesions exhibited thrombus (17%), ulceration (38%), and plaque rupture (28%). Sixty-two patients were treated with warfarin and aspirin and 30 with ticlid and aspirin. Complications included death in three patients (3.3%) who sustained subacute stent thrombosis, and two of three had Q-wave MI. Distal embolization occurred in seven patients (8%); six of seven sustained a non Q-wave acute myocardial infarction (AMI); and one of seven a Q-wave MI. Eight (9%) patients had major groin hematoma, two had pseudoaneurysm (2.2%), one had arteriovenous (A-V) fistula (1.1%), two had vascular surgery (2.2%), nine had blood transfusion (9.8%), and three had stent migration (3.3%). Single-center experience with stents in SVGs indicates a highly successful procedural and angiographic immediate result. However, it was complicated by significant risk of non Q-wave MI due to distal coronary embolization which may affect prognosis. 相似文献
9.
High-dose etoposide and cyclophosphamide without bone marrow transplantation for resistant hematologic malignancy 总被引:2,自引:1,他引:2
Brown RA; Herzig RH; Wolff SN; Frei-Lahr D; Pineiro L; Bolwell BJ; Lowder JN; Harden EA; Hande KR; Herzig GP 《Blood》1990,76(3):473-479
Seventy-five patients with resistant acute leukemia or lymphoma received high-dose cyclophosphamide and etoposide to explore the activity of this combination in resistant hematologic malignancies, and to determine the maximum doses of these drugs that can be combined without bone marrow transplantation. Etoposide was administered over 29 to 69 hours by continuous infusion corresponding to total doses of 1.8 g/m2 to 4.8 g/m2. Cyclophosphamide, 50 mg/kg/d, was administered on 3 or 4 consecutive days total 150 to 200 mg/kg ideal body weight). At all dose levels myelosuppression was severe but reversible. Mucosal toxicity was dose-limiting with the maximum tolerated dose level combining etoposide 4.2 g/m2 with cyclophosphamide 200 mg/kg. Continuous etoposide infusion produced stable plasma levels that were lower than would be achieved after administration by short intravenous infusion, and this could explain our ability to escalate etoposide above the previously reported maximum tolerated dose. There were 28 complete (35%) and 12 partial (16%) responses. Median duration of complete response (CR) was 3.5 months (range 1.1 to 20+). Seventeen of 40 patients (42%) with acute myelogenous leukemia (AML) achieved CR, including 6 of 20 (30%) with high-dose cytosine arabinoside resistance. We conclude that bone marrow transplantation is not required after maximum tolerated doses of etoposide and cyclophosphamide. This regimen is active in resistant hematologic neoplasms, and the occurrence of CR in patients with high-dose cytosine arabinoside-resistant AML indicates a lack of complete cross-resistance between these regimens. 相似文献
10.
Kuhn MA Jutzy KR Deming DD Cephus CE Chinnock RE Johnston J Bailey LL Larsen RL 《Journal of the American College of Cardiology》2000,36(1):250-254
OBJECTIVES: The study purposes were to determine 1) whether intravascular ultrasound (IVUS) was more sensitive than angiography for the detection of post-transplant coronary artery disease (PTCAD) in pediatric patients; and 2) whether those transplanted as neonates reacted differently than older patients. BACKGROUND: Experience with IVUS for the diagnosis of PTCAD in children is limited. METHODS: Patients were divided into two groups: those transplanted as neonates (early group) and those transplanted in infancy or childhood (late group). Morphometric analysis was performed, including maximal intimal thickness (MIT) and intimal index (II). Stanford classification was used to grade lesion severity. Acute rejection and cytomegalovirus (CMV) status were correlated with MIT and II. RESULTS: Thirty children were studied (early group, n = 13; late group, n = 17). All segments studied were angiographically normal. Mean MIT and mean II were significantly greater in the late group (0.26 +/- 0.14 vs. 0.13 +/- 0.04 mm, p < 0.001 and 0.11 +/- 0.07 vs. 0.07 +/- 0.03 mm, p = 0.04, respectively). There was a significant correlation between MIT and II in those who had acute rejection in the late group. Patients in the late group who were CMV-positive had a significantly higher MIT compared with those in the late group with negative serology (p = 0.04). CONCLUSIONS: Intravascular ultrasound was more sensitive than angiography in detecting PTCAD after pediatric heart transplantation. There is a possible role for acute rejection and CMV in the development of PTCAD. 相似文献