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21.
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
22.
23.
Gontijo AM Marcondes JP Elias FN de Oliveira ML de Lima RO Salvadori DM de Camargo JL 《Environmental and molecular mutagenesis》2002,40(3):190-199
In order to determine if patients with a history of previous urothelial cell carcinoma (UCC) but with current normal urinary cytology have DNA damage in urothelial cells, the single-cell gel electrophoresis (comet) assay was conducted with cells obtained by urinary bladder washings from 44 patients (28 with a history of previous UCC). Increased DNA damage was observed in cytologically "normal" urothelial cells of patients with a history of UCC when compared with referents with no similar history and after correcting the data for smoking status and age (P < 0.018). Increased DNA damage also correlated with the highest tumor grade, irrespective of time or course of the disease after clinical intervention (Kendall tau correlation, 0.37, P = 0.016). Moreover, aneuploidy, as assessed by DNA content ratio (DCR; 75th/25th percentile of total DNA fluorescence of 50 comets/patient) was unaltered by smoking status, but increased with UCC grade: 1.39 +/- 0.12 (median +/- 95% confidence interval; referents); 1.43 +/- 0.11 (Grade I UCC; P = 0.264, against referents); 1.49 +/- 0.16 (Grade II UCC; P = 0.057); 1.57 +/- 0.16 (Grade III UCC; P = 0.003). Micronucleated urothelial cells (MNC) were also scored on Giemsa-stained routine cytological smears and were found not to correlate with DNA damage or DCR. MNC frequencies were higher for patients with a history of UCC and/or smoking than referents with neither history, but there was no statistical difference between groups. Taken together, these results suggest that the normal-appearing urothelium of patients resected for UCC still harbor genetically unstable cells. 相似文献
24.
Morphological analysis of degeneration and regeneration of syncytiotrophoblast in first trimester placental villi during organ culture 总被引:3,自引:1,他引:3
We have recently shown using dansyl-L-lysine exclusion studies that the
release of human chorionic gonadotrophin (HCG) in conjunction with L-
lactate dehydrogenase (LDH) from first trimester villi during organ culture
is symptomatic of syncytiotrophoblast degeneration. The purpose of this
study was to examine chorionic villi at the ultrastructural level in order
to determine events occurring during organ culture. The tissue was sampled
after 0, 24, 48 and 120 h in culture and processed for electron microscopy.
In addition to confirming the previously recorded syncytial degeneration,
the electron micrographs showed clearly the generation of a new
syncytiotrophoblast layer. The new layer, derived from differentiating
cytotrophoblast cells, was largely formed by 48 h and was maintained for at
least 120 h in culture. This study demonstrates a model which provides an
opportunity to study the differentiation of cytotrophoblast cells whilst
they retain their anatomical relationships within the villous structure.
相似文献
25.
26.
27.
Aims : To evaluate the clinicopathological profile of 14 cases of nasal and paranasal sinusal adenocarcinoma, and to assess the usefulness of immunohistochemistry in the differential diagnosis of primary and metastatic intestinal-type adenocarcinoma.
Methods and results : Fourteen cases of nasal and paranasal adenocarcinoma, treated at IPOFG, Lisbon, between 1976 and 2002, were studied. Clinical records were reviewed and expression of cytokeratin (CK)7 and CK20 and of neuroendocrine markers was evaluated. The male : female ratio was 3 : 1, and the mean age of the patients was 65.3 years. Ten cases occurred in the paranasal sinuses. There was a history of professional exposure to dust in three patients. Twelve cases were high-grade intestinal type adenocarcinomas (ITAC) and two were low-grade. CK7 was present in 2/9 ITAC cases and CK20 in 8/9 ITAC and in cases of mixed and mucinous histology. All high-grade cases showed neuroendocrine differentiation. Seven of the 12 patients with high-grade adenocarcinoma died of the disease, with a mean follow-up of 47.4 months.
Conclusions : Nasal and paranasal adenocarcinoma mostly occurs in men in the 7th decade. ITAC is the most frequent histological type. The pattern of CK7/CK20 was not useful in the distinction between primary and metastatic intestinal adenocarcinoma. However, in the former, neuroendocrine differentiation proved to be a valuable tool in that distinction. 相似文献
Methods and results : Fourteen cases of nasal and paranasal adenocarcinoma, treated at IPOFG, Lisbon, between 1976 and 2002, were studied. Clinical records were reviewed and expression of cytokeratin (CK)7 and CK20 and of neuroendocrine markers was evaluated. The male : female ratio was 3 : 1, and the mean age of the patients was 65.3 years. Ten cases occurred in the paranasal sinuses. There was a history of professional exposure to dust in three patients. Twelve cases were high-grade intestinal type adenocarcinomas (ITAC) and two were low-grade. CK7 was present in 2/9 ITAC cases and CK20 in 8/9 ITAC and in cases of mixed and mucinous histology. All high-grade cases showed neuroendocrine differentiation. Seven of the 12 patients with high-grade adenocarcinoma died of the disease, with a mean follow-up of 47.4 months.
Conclusions : Nasal and paranasal adenocarcinoma mostly occurs in men in the 7th decade. ITAC is the most frequent histological type. The pattern of CK7/CK20 was not useful in the distinction between primary and metastatic intestinal adenocarcinoma. However, in the former, neuroendocrine differentiation proved to be a valuable tool in that distinction. 相似文献
28.
Freitas RM Nascimento VS Vasconcelos SM Sousa FC Viana GS Fonteles MM 《Neuroscience letters》2004,365(2):102-105
The mechanism underlying the vulnerability of the brain to status epilepticus (SE) induced by pilocarpine remains unknown. Oxidative stress has been implicated in a variety of acute and chronic neurologic conditions, including SE. The present study was aimed at was investigating the changes in catalase activity after pilocarpine-induced seizures and SE. The Control group was treated with 0.9% saline (NaCl, subcutaneously (s.c.)) and sacrificed 1h after the treatment. Another group was treated with pilocarpine (400 mg/kg, s.c., Pilocarpine group) and sacrificed 1h after treatment. The catalase activity in the cerebellum, hippocampus, frontal cortex and striatum of Wistar rats was determined. The results have shown that pilocarpine administration and resulting SE produced a significant increase in the catalase activity in the hippocampus (36%), striatum (31%) and frontal cortex (15%) of treated adult rats. Nevertheless, in the adult rat cerebellum after SE induced by pilocarpine no change was observed in the catalase activity. Our results demonstrated a direct evidence of an increase in the activity of the scavenging enzyme (catalase) in different cerebral structures during seizure activity that could be responsible for eliminating oxygen free radicals and might be one of the compensatory mechanisms to avoid the development of oxidative stress during the establishment of SE induced by pilocarpine. Our reports also indicate clear regional differences in the catalase activity caused by pilocarpine-induced seizures and SE and the hippocampus might be the principal area affected and cerebellum does not modify for this parameter studied during epileptic activity. 相似文献
29.
A second locus (GLC3B) for primary congenital glaucoma (Buphthalmos) maps to the 1p36 region 总被引:10,自引:0,他引:10
Akarsu AN; Turacli ME; Aktan SG; Barsoum-Homsy M; Chevrette L; Sayli BS; Sarfarazi M 《Human molecular genetics》1996,5(8):1199-1203
Primary congenital glaucoma (gene symbol: GLC3) is an ocular disorder that
occurs for 0.01-0.04% of blind people. In the majority of familial cases
reported so far, this condition is inherited as an autosomal recessive
trait. We have recently used a group of 17 GLC3 families with a minimum of
two affected offspring and consanguinity in most of the parental generation
and mapped the first GLC3 locus (GLC3A) to the 2p21 region. Six families
did not show any linkage to the GLC3A locus and thus provided evidence for
genetic heterogeneity of this disorder. A total of eight families unlinked
to the 2p21 region were used to search for the chromosomal location of the
second GLC3 locus. Herein, we describe mapping of a new locus (designated
GLC3B) for primary congenital glaucoma to the short arm of chromosome 1
(1p36.2-36.1) that is situated centromeric to the neuroblastoma and
Charcot-Marie-Tooth type 2A (CMT2A) loci. A total of 17 DNA markers were
genotyped from this region of chromosome 1. Four families showed no
recombination with the two markers D1S2834 and D1S402 with a maximum lod
score of 4.510 and 4.157 respectively. Pairwise and multipoint linkage
analysis and inspection of the haplotypes revealed that the remaining four
families are not linked to this part of chromosome 1, thus providing
further evidence that at least one more locus for the autosomal recessive
form of GLC3 must exist in the genome. Based on the recombination events,
the overall linkage map of this region is: tel-D1S1192-D1S1635-D1S1193 -
(D1S1597/-D1S489/D1S228)- [GLC3B/D1S2834/D1S402] - (D1S1176/D1S507/D1S407)
- D1S2728-(MFAP2/D1S170) - D1S1368 - D1S436- D1S1592-cen.
相似文献
30.
Striated intramural gallbladder lucencies on US studies: predictors of acute cholecystitis 总被引:1,自引:0,他引:1
Ultrasound scans of 51 consecutive patients with gallbladder wall thickening were reviewed, and specific sonographic features were correlated with surgical and clinical follow-up. Two patterns of thickening were identified as specific indicators of the presence or absence of acute cholecystitis. "Striated" wall thickening, consisting of several alternating, irregular, discontinuous, lucent and echogenic bands, was seen in eight of 13 patients (62%) with acute cholecystitis. This pattern was not encountered in any of the patients who did not have acute cholecystitis. Conversely, "three-layer" thickening, consisting of a single circumferential lucent zone between two relatively uniform echogenic layers, was seen in only one of 13 patients (8%) with acute cholecystitis but in 11 of 38 patients (29%) with other diagnoses. Other abnormalities, including the presence of intramural echogenic foci and wall irregularities, were more frequently seen in patients with acute cholecystitis but were not as helpful. Use of these features may suggest or help exclude a diagnosis of acute cholecystitis in those patients in whom the cause of gallbladder wall thickening is otherwise not apparent. 相似文献