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21.
Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation 总被引:22,自引:1,他引:22
Marsh DJ; Coulon V; Lunetta KL; Rocca-Serra P; Dahia PL; Zheng Z; Liaw D; Caron S; Duboue B; Lin AY; Richardson AL; Bonnetblanc JM; Bressieux JM; Cabarrot-Moreau A; Chompret A; Demange L; Eeles RA; Yahanda AM; Fearon ER; Fricker JP; Gorlin RJ; Hodgson SV; Huson S; Lacombe D; Eng C 《Human molecular genetics》1998,7(3):507-515
The tumour suppressor gene PTEN , which maps to 10q23.3 and encodes a 403
amino acid dual specificity phosphatase (protein tyrosine phosphatase;
PTPase), was shown recently to play a broad role in human malignancy.
Somatic PTEN deletions and mutations were observed in sporadic breast,
brain, prostate and kidney cancer cell lines and in several primary tumours
such as endometrial carcinomas, malignant melanoma and thyroid tumours. In
addition, PTEN was identified as the susceptibility gene for two hamartoma
syndromes: Cowden disease (CD; MIM 158350) and Bannayan-Zonana (BZS) or
Ruvalcaba-Riley-Smith syndrome (MIM 153480). Constitutive DNA from 37 CD
families and seven BZS families was screened for germline PTEN mutations.
PTEN mutations were identified in 30 of 37 (81%) CD families, including
missense and nonsense point mutations, deletions, insertions, a
deletion/insertion and splice site mutations. These mutations were
scattered over the entire length of PTEN , with the exception of the first,
fourth and last exons. A 'hot spot' for PTEN mutation in CD was identified
in exon 5 that contains the PTPase core motif, with 13 of 30 (43%) CD
mutations identified in this exon. Seven of 30 (23%) were within the core
motif, the majority (five of seven) of which were missense mutations,
possibly pointing to the functional significance of this region. Germline
PTEN mutations were identified in four of seven (57%) BZS families studied.
Interestingly, none of these mutations was observed in the PTPase core
motif. It is also worthy of note that a single nonsense point mutation,
R233X, was observed in the germline DNA from two unrelated CD families and
one BZS family. Genotype-phenotype studies were not performed on this small
group of BZS families. However, genotype-phenotype analysis inthe group of
CD families revealed two possible associations worthy of follow-up in
independent analyses. The first was an association noted in the group of CD
families with breast disease. A correlation was observed between the
presence/absence of a PTEN mutation and the type of breast involvement
(unaffected versus benign versus malignant). Specifically and more
directly, an association was also observed between the presence of a PTEN
mutation and malignant breast disease. Secondly, there appeared to be an
interdependent association between mutations upstream and within the PTPase
core motif, the core motif containing the majority of missense mutations,
and the involvement of all major organ systems (central nervous system,
thyroid, breast, skin and gastrointestinal tract). However, these
observations would need to be confirmed by studying a larger number of CD
families.
相似文献
22.
Stereoselective determination of cetirizine and studies on pharmacokinetics in rat plasma 总被引:2,自引:0,他引:2
Choi SO Lee SH Kong HS Kim EJ Choo HY 《Journal of chromatography. B, Biomedical sciences and applications》2000,744(1):201-206
Enantiomers may confer benefits over racemates in therapeutic uses and we developed a chiral separation method of cetirizine enantiomers, a second generation H1 histamine receptor antagonist, in rat plasma. alpha1-Acidglycoprotein based chiral stationary phase(AGP-CSP), monitored with UV at 230 nm was used to separate the enantiomers. Observed enantioselectivity (alpha) was 2.0. The AGP-CSP was also used at a preparative scale to isolate the enantiomers with an optical purity of greater than ee 99%. In addition, an analysis was carried out for the cetirizine enantiomers in rat plasma to study the differences of enantiomers in pharmacokinetics. Both (+)- and (-)-cetirizine were separated using a reversed-phase column of AGP, and were detected at the range of 2.5-200 microg ml(-1) in plasma. Although there was no recognizable differences in pharmacokinetics between the enantiomers in rat, the method appears to be useful for their pharmacokinetic studies. 相似文献
23.
The integration patterns of human papillomavirus (HPV) type 16 in the cellular DNA of six cervical carcinoma samples were analyzed by the Southern blot procedure. None of the HPV integrants retained the entire viral genome. Double HPV integration was found in one case while all other cases were single integrants. In some samples, internal deletion and selective amplification of the viral sequences were observed. On integration, the E2 open reading frame (ORF) was invariably lost but the E6/E7 ORFs and the long control region of the HPV-16 genome were retained in all seven integrations analyzed and may play a role in cellular transformation and/or maintenance of the transformed phenotype. 相似文献
24.
A novel chromatin immunoprecipitation and array (CIA) analysis identifies a 460-kb CENP-A-binding neocentromere DNA 总被引:17,自引:0,他引:17 下载免费PDF全文
Centromere protein A (CENP-A) is an essential histone H3-related protein that constitutes the specialized chromatin of an active centromere. It has been suggested that this protein plays a key role in the epigenetic marking and transformation of noncentromeric genomic DNA into functional neocentromeres. Neocentromeres have been identified on more than two-thirds of the human chromosomes, presumably involving different noncentromeric DNA sequences, but it is unclear whether some generalized sequence properties account for these neocentromeric sites. Using a novel method combining chromatin immunoprecipitation and genomic array hybridization, we have identified a 460-kb CENP-A-binding DNA domain of a neocentromere derived from the 20p12 region of an invdup (20p) human marker chromosome. Detailed sequence analysis indicates that this domain contains no centromeric alpha-satellite, classical satellites, or other known pericentric repetitive sequence motifs. Putative gene loci are detected, suggesting that their presence does not preclude neocentromere formation. The sequence is not significantly different from surrounding non-CENP-A-binding DNA in terms of the prevalence of various interspersed repeats and binding sites for DNA-interacting proteins (Topoisomerase II and High-Mobility-Group protein I). Notable variations include a higher AT content similar to that seen in human alpha-satellite DNA and a reduced prevalence of long terminal repeats (LTRs), short interspersed repeats (SINEs), and Alus. The significance of these features in neocentromerization is discussed. 相似文献
25.
Dynamic assessment of the electrocardiographic QT interval during citrate infusion in healthy volunteers. 总被引:1,自引:0,他引:1 下载免费PDF全文
T. M. Davis B. Singh K. E. Choo J. Ibrahim J. L. Spencer A. St John 《Heart (British Cardiac Society)》1995,73(6):523-526
OBJECTIVE--To investigate changes in the electrocardiographic QT interval during rapidly induced, sustained hypocalcaemia in healthy volunteers. DESIGN--Serial rate corrected QT measurements were made during and after a variable rate trisodium citrate infusion designed to "clamp" the whole blood ionised calcium concentration 0.20 mmol/l below baseline for 120 min. SUBJECTS--12 healthy teetotallers aged 19- 36 years who were not receiving medication known to influence calcium homoeostasis. MAIN OUTCOME MEASURES--Whole blood ionised calcium concentration and QaTc intervals (onset of the Q wave to T wave apex divided by the square root of the RR interval). RESULTS--Mean (SD) ionised calcium concentration decreased from 1.18 (0.03) mmol/l preinfusion to values close to target (0.98 mmol/l) between 10 and 120 min. The QaTc interval lengthened from a baseline of 0.309 (0.021) to a maximum 0.343 (0.024) s0.5 at 10 min before returning to a stable level from 15 to 120 min (0.334 (0.023) and 0.330 (0.023) s0.5 respectively). The change from baseline of both variables expressed as a ratio (delta QaTc/ delta [Ca2+]) was greater during rapid induction of hypocalcaemia (at 5 and 10 min) than at other times during and after the infusion (P < 0.02). CONCLUSIONS--The disproportionate prolongation of QaTc interval during prompt induction of hypocalcaemia suggests rate dependency which can be represented by a hysteresis relation between (ionised calcium, QaTc) coordinates. This finding may have clinical implications. 相似文献
26.
This survey sought to determine (a) the prevalence of carer stress in patients with mild to moderate dementia, (b) whether caregiver burden was already associated with plans to institutionalize patients, and (c) which patient-related and caregiver-related variables best predicted caregiver burden. The principal caregivers of 93 Asian patients with mild to moderate dementia attending an outpatient cognitive assessment clinic were interviewed via a structured questionnaire that focused upon (a) patient-related variables such as their behavioral and functional abnormalities; and (b) caregiver-related variables such as whether they were having problems looking after the patients, the duration of their caregiving, their associated feelings of anger and/or depression, and their financial status as well as intentions to institutionalize patients. Forty-nine percent of caregivers reported problems in looking after the patients, and their perception of difficulties was significantly associated with institutionalization plans for the patients. Logistic regression analysis using a forward variable selection procedure showed two of the patients' behavioral abnormalities (repetition, agitation) and one of their functional impairments (urinary incontinence) as well as the carers' depressed feelings to be predictive of the carers' problematic status, explaining 40% of the variance. It is important that even in the early stages of dementia, the medical assessment also evaluate behavioral, functional, and social dimensions of the illness, so that appropriate interventions can be implemented to reduce caregiving burden and delay institutionalization. 相似文献
27.
Exposure of expanded polytetrafluoroethylene-wrapped hydroxyapatite orbital implant: a report of two patients 总被引:2,自引:0,他引:2
Choo PH Carter SR Crawford JB Seiff SR 《Ophthalmic plastic and reconstructive surgery》1999,15(2):77-78
PURPOSE: Hydroxyapatite (HA) spheres used to replace volume after an enucleation are often wrapped with autologous tissue before orbital implantation. Man-made materials are less expensive and pose no risk for viral transmission. The use of expanded polytetrafluoroethylene (ePTFE) to wrap HA spheres was evaluated. METHODS: The medical records of 2 consecutive patients who underwent uncomplicated implantation of an HA sphere wrapped in ePTFE were reviewed. RESULTS: An unusual reaction to the ePTFE material that was nonresponsive to topical or systemic antibiotic therapy developed in these 2 patients. Eventual wound erosion and bacterial infection of the implant necessitated its removal. CONCLUSIONS: Although well tolerated in other surgeries, ePTFE, when used to wrap HA spheres and placed into the orbit, may cause persistent conjunctival discharge, pyogenic granuloma formation, and eventual wound erosion. Therefore, the use of this material to wrap HA spheres is not recommended. 相似文献
28.
Kim SY Lee KS Han J Kim J Kim TS Choo SW Kim SJ 《AJR. American journal of roentgenology》2000,174(3):795-798
OBJECTIVE: We describe the chest CT and pathologic findings of semiinvasive pulmonary aspergillosis in six patients. CONCLUSION: Semiinvasive pulmonary aspergillosis should be considered in the mildly immunocompromised patient with CT findings that reveal persistent parenchymal abnormalities. Patterns include consolidation and mass. 相似文献
29.
Youngmee Jung Sun-Hee Lee Sang-Heon Kim Jong Choo Lim 《Journal of biomaterials science. Polymer edition》2013,24(4):386-397
We synthesized a series of tri-component biodegradable copolymers with elastic characteristics by ring-opening copolymerization of cyclic lactones, that is, glycolide, L-lactide, and ?-caprolactone, in the presence of stannous octoate as a catalyst. We evaluated the physical and chemical characteristics of poly(glycolide-co-L-lactide-co-?-caprolactone) (PGLCL) copolymers. The synthesized PGLCL had a high molecular weight of about 100?kD and an amorphous structure. It was confirmed that the physical and chemical properties of these terpolymers could be modulated by adjusting copolymer composition. PGLCL films exhibited rubber-like elasticity and showed almost complete recovery when subjected to 50% of the tensile strain. To examine the biodegradability of the PGLCL copolymers, we performed in vitro degradation tests for 12?weeks and observed changes in molecular weight, gross weight, and composition. These results showed that the glycolide was degraded most quickly and that ?-caprolactone was the slowest to degrade. Additionally, cytotoxicity tests revealed that none of the polymers were toxic. In summary, the mechanical properties and biodegradability of PGLCL terpolymers could be controlled by changing the monomer content, which may be useful for a wide range of tissue engineering applications based on mechanical property requirements. 相似文献
30.
Muhammad Khurram Khan Mohammed Zakariah Hafiz Malik Kim-Kwang Raymond Choo 《The Australian journal of forensic sciences》2018,50(5):525-542
Today, digital multimedia (audio, video, images) is a common evidential source in litigation and criminal justice proceedings, and, not surprisingly, multimedia forensics is an active research area. One particular challenge faced by multimedia forensic researchers is the lack of a comprehensive and publicly available data-set for evaluating existing and new algorithms. This paper presents a digital audio forensic data-set, designed to facilitate evaluation of audio forensic algorithms (e.g. microphone identification, acoustic environment identification and splice detection). This paper also briefly describes the data-collection settings, microphones, speakers, languages and notations used. Existing tamper-detection techniques rely on artefacts due to recording devices, codec and/or the acoustic environment in the audio in question. Experimental results show that the selected approaches achieved promising results. 相似文献