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排序方式: 共有174条查询结果,搜索用时 15 毫秒
1.
A 12 year follow up study in the general population on prognostic factors of cartilage loss in osteoarthritis of the knee. 总被引:7,自引:0,他引:7
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J S Schouten F A van den Ouweland H A Valkenburg 《Annals of the rheumatic diseases》1992,51(8):932-937
The natural history and prognostic factors of cartilage loss in osteoarthritis of the knee were studied in subjects from a general population survey on rheumatic diseases in 1975-8. Baseline data were collected by questionnaire, physical examination, and weightbearing anteroposterior knee radiographs. Follow up of the subjects aged 46-68 years with radiological osteoarthritis grade 2-4 (Kellgren) took place in 1988-9. Cartilage loss was assessed by two observers who scored the change in joint space width between two radiographs. Thirty four per cent had cartilage loss. Prognostic factors and adjusted odds ratios (ORs) (95% confidence intervals) were: body mass index OR = 11.1 (3.3 to 37.3) fourth v first quartile; body weight OR = 7.9 (2.6 to 24.0) third v first tertile; age OR = 3.8 (1.1 to 13.4) > 60 v < or = 49 years; Heberden's nodes OR = 6.0 (1.5 to 23.1); clinical diagnosis of generalised osteoarthritis OR = 3.3 (1.3 to 8.3); and previous bow legs or knock knees OR = 5.1 (1.1 to 23.1). The relation of age with cartilage loss was also confounded by the presence of Heberden's nodes or a diagnosis of generalised osteoarthritis. There was no statistically significant relation for gender, meniscectomy, injury, uric acid concentration, chondrocalcinosis, smoking, and occupation related factors, except possibly standing. 相似文献
2.
van Slegtenhorst M; Nellist M; Nagelkerken B; Cheadle J; Snell R; van den Ouweland A; Reuser A; Sampson J; Halley D; van der Sluijs P 《Human molecular genetics》1998,7(6):1053-1057
Tuberous sclerosis (TSC) is an autosomal dominant disorder caused by a
mutation in either the TSC1 or TSC2 tumour suppressor gene. The disease is
characterized by a broad phenotypic spectrum that can include seizures,
mental retardation, renal dysfunction and dermatological abnormalities.
TSC2 encodes tuberin, a putative GTPase activating protein for rap1 and
rab5. The TSC1 gene was recently identified and codes for hamartin, a novel
protein with no significant homology to tuberin or any other known
vertebrate protein. Here, we show that hamartin and tuberin associate
physically in vivo and that the interaction is mediated by predicted
coiled-coil domains. Our data suggest that hamartin and tuberin function in
the same complex rather than in separate pathways.
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3.
Prenatal diagnosis of the fragile X syndrome: loss of mutation owing to a double recombinant or gene conversion event at the FMR1 locus.
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M Losekoot E Hoogendoorn R Olmer C C Jansen J C Oosterwijk A M van den Ouweland D J Halley S T Warren R Willemsen B A Oostra E Bakker 《Journal of medical genetics》1997,34(11):924-926
The fragile X syndrome, an X linked mental retardation syndrome, is caused by an expanded CGG repeat in the first exon of the FMR1 gene. In patients with an expanded repeat the FMR1 promoter is methylated and, consequently, the gene is silenced and no FMR1 protein (FMRP) is produced, thus leading to the clinical phenotype. Here we describe a prenatal diagnosis performed in a female from a fragile X family carrying a large premutation. In chorionic villus DNA of the male fetus the normal maternal CGG allele and a normal pattern on Southern blot analysis were found in combination with the FRAXAC2 and DXS297 allele of the maternal at risk haplotype. A second chorionic villus sampling was performed giving identical results on DNA analysis and, in addition, expression of FMRP was shown by immunohistochemistry. We concluded that the male fetus was not affected with the fragile X syndrome. Subsequent detailed haplotype analysis showed a complex recombination pattern resembling either gene conversion or a double crossover within a 20 kb genomic region. 相似文献
4.
Determination of the parent of origin in nine cases of prenatally detected chromosome aberrations found after intracytoplasmic sperm injection 总被引:1,自引:17,他引:1
Van Opstal D; Los FJ; Ramlakhan S; Van Hemel JO; Van Den Ouweland AM; Brandenburg H; Pieters MH; Verhoeff A; Vermeer MC; Dhont M; In't Veld PA 《Human reproduction (Oxford, England)》1997,12(4):682-686
Prenatal cytogenetic analysis of 71 fetuses conceived by intracytoplasmic
sperm injection (ICSI) resulted in the detection of nine (12.7%) chromosome
aberrations including two cases of 47,XXY, four cases involving a 45,X cell
line and three autosomal trisomies. Molecular analysis of the parental
origin of the deleted or supernumerary chromosome was performed by using
polymorphic microsatellite markers. Six cases involving a sex chromosome
abnormality were found to be of paternal origin while the two trisomic
cases that could be analysed were of maternal origin. Two cases involved
the same infertile couple who had two consecutive ICSI pregnancies
terminated because of a chromosome abnormality. The replaced embryos in
both cases originated from a single batch of ICSI fertilized oocytes of
which part was used to initiate the first pregnancy and part was
cryopreserved and used to initiate the second pregnancy.
相似文献
5.
Wang Q Verhoef S Tempelaars AM Bakker PL Vrtel R Hesseling-Janssen AL Nellist M Oranje AP Stroink H Lindhout D Halley DJ van den Ouweland AM 《Human mutation》1998,11(4):331-332
Important symptoms of tuberous sclerosis complex (TSC), an autosomal dominant disorder, are hamartomata in several organs, mental retardation and epilepsy. Either one of two loci can be involved (TSC1 and TSC2), of which the TSC2 gene has been cloned. To date, only 35 mutations in the TSC2 gene have been described ranging from large deletions to point mutations. Southern blot analysis using cDNA clones of the TSC2 gene was performed on a cohort of 160 unrelated TSC patients and revealed a 10 kb insertion. The insertion was also present in DNA of the affected father. Both patients showed renal angiomyolipoma, hypomelanotic macules and epilepsy. SSCP analysis of exons 1,2,3,9,12,14,30a and 36 identified two mutations in exon 30a: 3671del8 and S1221X. Symptoms of the sporadic patient with the 3671del8 mutation are cortical tubers, subependymal nodules, facial angiofibroma, ungual fibroma, renal angiomyolipoma, hypomelanotic macules, epilepsy and mental retardation. Clinical symptoms of the patient with the S1221X mutation are facial angiofibroma, ungual fibroma, hypomelanotic macules, epilepsy and mental retardation. His parents were negative for the S1221X mutation, although a germline mosaicism can not be excluded. Besides the previously described polymorphism 1596C->T, two rare variants were observed, a substitution of C->T at position 1294 and at position 1299 C->A. 相似文献
6.
Jingmei Li Keith Humphreys Tuomas Heikkinen Kristiina Aittom?ki Carl Blomqvist Paul D. P. Pharoah Alison M. Dunning Shahana Ahmed Maartje J. Hooning John W. M. Martens Ans M. W. van den Ouweland Lars Alfredsson Aarno Palotie Leena Peltonen-Palotie Astrid Irwanto Hui Qi Low Garrett H. K. Teoh Anbupalam Thalamuthu Douglas F. Easton Heli Nevanlinna Jianjun Liu Kamila Czene Per Hall 《Breast cancer research and treatment》2011,126(3):717-727
In an attempt to identify common disease susceptibility alleles for breast cancer, we performed a combined analysis of three genome-wide association studies (GWAS), involving 2,702 women of European ancestry with invasive breast cancer and 5,726 controls. Tests for association were performed for 285,984 SNPs. Evidence for association with SNPs in genes in specific pathways was assessed using a permutation-based approach. We confirmed associations with loci reported by previous GWAS on 1p11.2, 2q35, 3p, 5p12, 8q24, 10q23.13, 14q24.1 and 16q. Six SNPs with the strongest signals of association with breast cancer, and which have not been reported previously, were typed in two further studies; however, none of the associations could be confirmed. Suggestive evidence for an excess of associations was found for genes involved in the regulation of actin cytoskeleton, glycan degradation, alpha-linolenic acid metabolism, circadian rhythm, hematopoietic cell lineage and drug metabolism. Androgen and oestrogen metabolism, a pathway previously found to be associated with the development of postmenopausal breast cancer, was marginally significant (P = 0.051 [unadjusted]). These results suggest that further analysis of SNPs in these pathways may identify associations that would be difficult to detect through agnostic single SNP analyses. More effort focused in these aspects of oncology can potentially open up promising avenues for the understanding of breast cancer and its prevention. 相似文献
7.
Chantal Lammens Eveline Bleiker Neil Aaronson Annette Vriends Margreet Ausems Maaike Jansweijer Anja Wagner Rolf Sijmons Ans van den Ouweland Rob van der Luijt Liesbeth Spruijt Encarna Gómez García Mariëlle Ruijs Senno Verhoef 《Familial cancer》2009,8(4):457-464
The use of pre-implantation genetic diagnosis (PGD) for hereditary cancer is subject to on-going debate, particularly among professionals. This study evaluates the attitude towards PGD and attitude-associated characteristics of those concerned: family members with a hereditary cancer predisposition. Forty-eight Von Hippel-Lindau and 18 Li–Fraumeni Syndrome families were identified via the 9 family cancer clinics in the Netherlands. In total, 216 high risk family members and partners were approached, of whom 179 (83%) completed a self-report questionnaire. Of the high risk family members, 35% expressed a positive attitude towards PGD. Those with a current desire to have children were significantly more likely to have a positive attitude: 48% would consider the use of PGD. No other sociodemographic, medical or psychosocial variables were associated significantly with a positive attitude. The most frequently reported advantage of PGD is the avoidance of a possible pregnancy termination. Uncertainty about late effects was the most frequently reported disadvantage. These results indicate that approximately half of those contemplating a future pregnancy would consider the use of PGD. The actual uptake, however, is expected to be lower. There is no indication that psychosocial factors affect interest in PGD. 相似文献
8.
Ipsilateral breast tumour recurrence in hereditary breast cancer following breast-conserving therapy
Seynaeve C Verhoog LC van de Bosch LM van Geel AN Menke-Pluymers M Meijers-Heijboer EJ van den Ouweland AM Wagner A Creutzberg CL Niermeijer MF Klijn JG Brekelmans CT 《European journal of cancer (Oxford, England : 1990)》2004,40(8):1150-1158
The overall rate of an ipsilateral breast tumour recurrence (IBTR) after breast-conserving therapy (BCT) ranges from 1% to 2% per year. Risk factors include young age but data on the impact of BRCA1/2 mutations or a definite positive family history for breast cancer are scarce. We investigated IBTR after BCT in patients with hereditary breast cancer (HBC). Through our family cancer clinic we identified 87 HBC patients, including 26 BRCA1/2 carriers, who underwent BCT between 1980 and 1995 (cases). They were compared to 174 patients with sporadic breast cancer (controls) also treated with BCT, matched for age and year of diagnosis. Median follow up was 6.1 years for the cases and 6.0 years for controls. Patient and tumour characteristics were similar in both groups. An IBTR was observed in 19 (21.8%) hereditary and 21 (12.1%) sporadic patients. In the hereditary patients more recurrences occurred elsewhere in the breast (21% versus 9.5%), suggestive of new primaries. Overall, the actuarial IBTR rate was similar at 2 years, but higher in hereditary as compared to sporadic patients at 5 years (14% versus 7%) and at 10 years (30% versus 16%) (P=0.05). Post-relapse and overall survival was not different between hereditary and sporadic cases. Hereditary breast cancer was therefore associated with a higher frequency of early (2-5 years) and late (>5 years) local recurrences following BCT. These data suggest an indication for long-term follow up in HBC and should be taken into account when additional 'risk-reducing' surgery after primary BCT is eventually considered. 相似文献
9.
Marianne Hoogeveen‐Westerveld Rosemary Ekong Sue Povey Karin Mayer Nathalie Lannoy Frances Elmslie Martina Bebin Kira Dies Catherine Thompson Steven P. Sparagana Peter Davies Ans van den Ouweland Dicky Halley Mark Nellist 《Human mutation》2013,34(1):167-175
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in the TSC1 or TSC2 genes. The TSC1 and TSC2 gene products, TSC1 and TSC2, form a complex that inhibits the mammalian target of rapamycin (mTOR) complex 1 (TORC1). Here, we investigate the effects of 78 TSC2 variants identified in individuals suspected of TSC, on the function of the TSC1–TSC2 complex. According to our functional assessment, 40 variants disrupted the TSC1–TSC2‐dependent inhibition of TORC1. We classified 34 of these as pathogenic, three as probably pathogenic and three as possibly pathogenic. In one case, a likely effect on splicing as well as an effect on function was noted. In 15 cases, our functional assessment did not agree with the predictions of the SIFT amino acid substitution analysis software. Our data support the notion that different, nonterminating TSC2 mutations can have distinct effects on TSC1–TSC2 function, and therefore, on TSC pathology. 相似文献