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排序方式: 共有126条查询结果,搜索用时 31 毫秒
1.
Abou-Zahr F Bejjani B Kruyt FA Kurg R Bacino C Shapira SK Youssoufian H 《American journal of medical genetics》1999,83(5):388-391
Seckel syndrome is a rare autosomal recessive disorder. The classical presentation includes pre- and postnatal growth deficiency, mental retardation, and characteristic facial appearance. There have been several reports of associated hematological abnormalities and chromosomal breakage, findings suggestive of Fanconi anemia (FA). We tested for these findings in two Arabic patients with this syndrome. We compared the growth profile of lymphoblastoid cells from our patients and their parents with the FA group A cell line HSC72 in the presence and absence of mitomycin C (MMC). By Western analysis, we also determined the expression of FAA and FAC, two FA disease gene products that together account for approximately 80% of FA. Unlike HSC72 cells, cells from the patients were resistant to MMC, and both FAA and FAC proteins were expressed at similar levels in all cell lines. There is an increasing recognition of clinical variability and perhaps genetic heterogeneity in Seckel syndrome. Our results demonstrate that cross-link sensitivity comparable to FA is not a uniform finding in patients with Seckel syndrome. 相似文献
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3.
Transgenic rat model of Huntington's disease 总被引:12,自引:0,他引:12
von Hörsten S Schmitt I Nguyen HP Holzmann C Schmidt T Walther T Bader M Pabst R Kobbe P Krotova J Stiller D Kask A Vaarmann A Rathke-Hartlieb S Schulz JB Grasshoff U Bauer I Vieira-Saecker AM Paul M Jones L Lindenberg KS Landwehrmeyer B Bauer A Li XJ Riess O 《Human molecular genetics》2003,12(6):617-624
Huntington's disease (HD) is a late manifesting neurodegenerative disorder in humans caused by an expansion of a CAG trinucleotide repeat of more than 39 units in a gene of unknown function. Several mouse models have been reported which show rapid progression of a phenotype leading to death within 3-5 months (transgenic models) resembling the rare juvenile course of HD (Westphal variant) or which do not present with any symptoms (knock-in mice). Owing to the small size of the brain, mice are not suitable for repetitive in vivo imaging studies. Also, rapid progression of the disease in the transgenic models limits their usefulness for neurotransplantation. We therefore generated a rat model transgenic of HD, which carries a truncated huntingtin cDNA fragment with 51 CAG repeats under control of the native rat huntingtin promoter. This is the first transgenic rat model of a neurodegenerative disorder of the brain. These rats exhibit adult-onset neurological phenotypes with reduced anxiety, cognitive impairments, and slowly progressive motor dysfunction as well as typical histopathological alterations in the form of neuronal nuclear inclusions in the brain. As in HD patients, in vivo imaging demonstrates striatal shrinkage in magnetic resonance images and a reduced brain glucose metabolism in high-resolution fluor-deoxy-glucose positron emission tomography studies. This model allows longitudinal in vivo imaging studies and is therefore ideally suited for the evaluation of novel therapeutic approaches such as neurotransplantation. 相似文献
4.
The bovine papillomavirus (BPV-1) E2 protein is the regulator of extrachromosomal replication of papillomaviruses. The mutants with C-terminal truncations and in-frame internal deletions were constructed to study the role of structural domains of E2 in the initiation of DNA replication. We show that the replication initiation function of E2 is absolutely dependent on the ability of the protein to bind to DNA. Our study also confirms the borders of the functional domains of the E2 protein; residues 1-192 form the activation domain and residues 310-410 the DNA binding-dimerization domain. Some critical length and flexibility, but not the particular amino acid sequence between these two functional domains is required for the activity of the protein to support replication. The hinge region, including the major phosphorylation sites of E2, is also dispensable for the mediation of attachment of the BPV1 genome to the mitotic chromosomes. 相似文献
5.
BACKGROUND/AIMS: To investigate changes in the histology and the Helicobacter pylori (H. pylori) prevalence and density of the gastric mucosa, as well as in fasting serum gastrin and serum pepsinogen I, depending on completeness of vagotomy, and in cases of recurrent ulcer, during 14 years after operation in duodenal ulcer patients. METHODOLOGY: 122 vagotomized duodenal ulcer patients were studied twice on average 9 and 14 years after operation. The presence of recurrent ulcer and completeness of vagotomy were assessed simultaneously endoscopically and by endoscopic Congo red test. The histology of the gastric antrum and corpus mucosa was assessed in accordance with the Sydney system. The amount of H. pylori in the specimens was detected by microscopic counting; gastrin and pepsinogen I in serum were determined radioimmunologically. RESULTS: During the 14-year follow-up period, complete vagotomy patients were characterized by a smaller amount of active antrum gastritis and a larger amount of active chronic corpus gastritis involving corpus atrophy in 46% of cases 14 years after operation. Recurrent ulcer patients were characterized by a significantly higher prevalence of high-grade H. pylori colonization and active mucosal inflammation in the antrum as well as by a lower level of active mucosal inflammation and atrophy in the corpus and a higher serum pepsinogen I level compared with complete vagotomy cases. The data of incomplete vagotomy patients without recurrent ulcer became more similar to those recorded for recurrent ulcer patients. CONCLUSIONS: In duodenal ulcer patients, changes in the histology of the gastric antrum and corpus mucosa as well as in H. pylori prevalence and density and in serum pepsinogen I levels are different depending on completeness of vagotomy during 14 years after operation. 相似文献
6.
Two de novo cases with Apert Syndrome detected prenatally are presented herein. In the first, fetal ultrasound findings of syndactyly of the hands, craniosynostosis and proptosis resulted in a prenatal diagnosis in the nineteenth week of gestation. This is the earliest prenatal diagnosis of this syndrome in a not-at-risk case. Following counseling, this pregnancy was terminated and subsequent pathological examination and DNA analysis confirmed the diagnosis of Apert Syndrome and coarctation of the aorta. In the second case, fetal ultrasound at 21 weeks' gestation revealed a hypoplastic left heart and clover-leaf skull. Following counseling, this pregnancy was also terminated. Further examination of the fetus and DNA analysis led to a diagnosis of Apert Syndrome. These cases emphasize the need to complete a thorough fetal ultrasound in cases with potentially lethal cardiac abnormality and the importance of incorporating a fetal pathologist, as well as a medical geneticist, in the investigations performed after delivery or pregnancy termination when a fetal abnormality is detected on ultrasound. 相似文献
7.
A phase I trial of adenovector-mediated delivery of interleukin-2 (AdIL-2) in high-risk localized prostate cancer 总被引:1,自引:0,他引:1
Trudel S Trachtenberg J Toi A Sweet J Li ZH Jewett M Tshilias J Zhuang LH Hitt M Wan Y Gauldie J Graham FL Dancey J Stewart AK 《Cancer gene therapy》2003,10(10):755-763
Preclinical studies demonstrate that intratumoral delivery of adenovirus expressing IL-2 eradicates pre-established tumors in mice and confers immune protection from rechallenge. To explore the activity of AdCAIL-2 in prostate cancer, a Phase I clinical trial was conducted in patients with localized disease and Gleason score >7 or prostate-specific antigen (PSA) >10 plus Gleason score 7. A total of 12 patients were injected 4 weeks prior to prostatectomy in a dose-escalation study at doses of 10(9), 5 x 10(9) and 10(10) PFU of virus. No dose-limiting toxicity was observed. Side effects included perineal discomfort, hematuria, flu-like symptoms in two patients and urinary hesitancy in one patient. Pathology demonstrated an inflammatory response consisting predominantly of CD3+CD8+ T lymphocytes with areas of tumor necrosis. Intracellular cytokine staining of tumor-infiltrating lymphocytes demonstrated increases in both gamma-interferon and IL-4 secreting T cells after vaccination. PSA levels fell in five of five evaluable patients treated at the lowest dose (mean decline of 33.3%, range 17-69%). At higher doses, PSA values initially increased after injection, then fell to baseline prior to surgery. This trial demonstrates the feasibility and safety of intraprostatic adenovector-mediated IL-2 gene delivery. 相似文献
8.
Koumbaris G Hatzisevastou-Loukidou H Alexandrou A Ioannides M Christodoulou C Fitzgerald T Rajan D Clayton S Kitsiou-Tzeli S Vermeesch JR Skordis N Antoniou P Kurg A Georgiou I Carter NP Patsalis PC 《Human molecular genetics》2011,20(10):1925-1936
The recently described DNA replication-based mechanisms of fork stalling and template switching (FoSTeS) and microhomology-mediated break-induced replication (MMBIR) were previously shown to catalyze complex exonic, genic and genomic rearrangements. By analyzing a large number of isochromosomes of the long arm of chromosome X (i(Xq)), using whole-genome tiling path array comparative genomic hybridization (aCGH), ultra-high resolution targeted aCGH and sequencing, we provide evidence that the FoSTeS and MMBIR mechanisms can generate large-scale gross chromosomal rearrangements leading to the deletion and duplication of entire chromosome arms, thus suggesting an important role for DNA replication-based mechanisms in both the development of genomic disorders and cancer. Furthermore, we elucidate the mechanisms of dicentric i(Xq) (idic(Xq)) formation and show that most idic(Xq) chromosomes result from non-allelic homologous recombination between palindromic low copy repeats and highly homologous palindromic LINE elements. We also show that non-recurrent-breakpoint idic(Xq) chromosomes have microhomology-associated breakpoint junctions and are likely catalyzed by microhomology-mediated replication-dependent recombination mechanisms such as FoSTeS and MMBIR. Finally, we stress the role of the proximal Xp region as a chromosomal rearrangement hotspot. 相似文献
9.
Andreson H Sillakivi T Peetsalu M Peetsalu A Mikelsaar M 《Scandinavian journal of gastroenterology》2007,42(3):324-329
OBJECTIVE: In patients with perforated peptic ulcer (PPU) the convergence between the high eradication rate of Helicobacter pylori infection and low rates of ulcer relapse after treatment has been associated with reinfection by non-virulent strains. The objective of this study was to evaluate the persistence of infection by virulent H. pylori strains and ulcer recurrence in 33 patients with PPU one year after surgery and antimicrobial treatment. MATERIAL AND METHODS: The histological evaluation and molecular detection of H. pylori cagA and ureA genes, vacA allelic types and the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analyses of the glmM gene products from antral mucosa specimens were performed initially, 2-5 months and 1 year after therapy. RESULTS: The density of H. pylori colonization was temporarily decreased (p<0.05) 2-5 months after therapy. After one year, complete eradication was achieved in only 7 patients (23%) at histological examination and recurrent ulcers were found in 3/33 (9%) patients. The vacA s1a allelic type of cagA-positive strains persisted in 19/33 (58%) PPU patients with identical PCR-RFLP fingerprints in 8/9 (89%) of the patients. CONCLUSIONS: In PPU patients with a low eradication rate of H. pylori infection after surgical and antimicrobial treatment, the frequent recrudescence of the infection is mostly caused by the persisting virulent strains of the cagA and vacA s1a subtypes. In the 1-year follow-up period the recurrent ulceration can be postponed just by the lowered colonization density of H. pylori after eradicative therapy. 相似文献
10.