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11.
Rosenberg C Wouters CH Szuhai K Dorland R Pearson P Poll-The BT Colombijn RM Breuning M Lindhout D 《European journal of human genetics : EJHG》2001,9(3):171-177
Rett syndrome (RTT) is an X-linked neurodevelopmental disorder, characterised by regression of development in young females. Recently, mutations in the MECP2 gene were found to be present in 80% of sporadic cases, but in much lower frequency (< 30%) among familial cases. Several reports claim that the pattern of X chromosome inactivation (XCI) relates to the penetrance of RTT; in some cases skewed XCI is seen in Rett patients, and in others it is observed among normal carriers. We present here a case of RTT with a 46,X,r(X) in which complete skewed inactivation of the ring was demonstrated. Further, no mutations were found in the MECP2 gene present on the intact X. Our data, in conjunction with two previously published cases of X chromosome abnormalities in RTT, indicate that X chromosome rearrangements are sporadically associated with RTT in conjunction with extreme skewing of X inactivation. Based on our case and reported data, we discuss the evidence for a second X-linked locus for RTT associated with lower penetrance, and a different pattern of XCI, than for MECP2. This would result in a larger proportion of phenotypically normal carrier women transmitting the mutation for this putative second locus, and account for the minority of sporadic and majority of familial cases that are negative for MECP2 mutations. 相似文献
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Lack of PTEN expression in endometrial intraepithelial neoplasia is correlated with cancer progression 总被引:6,自引:0,他引:6
Baak JP Van Diermen B Steinbakk A Janssen E Skaland I Mutter GL Fiane B Løvslett K 《Human pathology》2005,36(5):555-561
We tested the hypothesis that PTEN inactivation may stratify cancer progression risk among putative endometrial hyperplasias, classified prognostically by means of the morphometric D score (DS). The DS, calculated from 3 morphometric variables measured in routine hematoxylin-eosin-stained endometrial biopsy slides, is the most sensitive and specific method of endometrial cancer risk prediction currently available. Clinical outcomes of 103 women with endometrial hyperplasia on biopsy were tallied according to the DS. Seven (7/103; 7%) patients with carcinoma during follow-up were all distributed within the high-risk prognostic group (ie, DS <1 = endometrial intraepithelial neoplasia [EIN]) (7/21; 33% progression). None of the 82 cases with a DS higher than 1 progressed. All cases that progressed were PTEN null, indicating that this genotype is capable of further stratifying cancer progression risk in hyperplasias irrespective of histological categorization. However, only 16% of the PTEN-null cases progressed. When PTEN expression pattern was combined with EIN, the prognostic power was greatly increased (specificity from 63% for PTEN and 85% for EIN to 93% when combined; positive predictive value from 16% and 33% to 50%). We conclude that loss of PTEN expression is the first biomarker in EIN that increases the accuracy of the prognostic DS to predict cancer progression risk. Unless endometrial hyperplasias are stratified by histological morphometric D-Score, PTEN has a low positive predictive value. 相似文献
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The major goal of the present work is to further approach the structure of human monoamine oxidase A (MAO-A). A first partial three-dimensional model of human MAO-A has already been established using secondary structure predictions and fold recognition methods [Wouters and Baudoux, 1998]. In this modeled structure, a segment of the sequence (residues 369-393) located near the covalent linkage to the essential flavin cofactor, and potentially involved in the structure of the active site of the protein, could not be modeled. We here propose a possible fold for that segment, based on threading techniques. The identification of regions of the protein potentially involved in its dimerization was also undertaken by studying hydrophobic areas present at the surface of the structure. 相似文献
16.
Bradley R Pieters Augustinus A M Hart Nicola S Russell Edwin P M Jansen Johannes L Peterse Jacques Borger Emiel J Th Rutgers 《Radiotherapy and oncology》2003,67(2):159-164
BACKGROUND AND PURPOSE: Interstitial implants for brachytherapy boost in the breast conserving therapy of breast cancer can be performed in two ways; implants during the tumor excision (per-operative implants) or after the external beam therapy (delayed interstitial implants). Differences in cosmetic outcome were investigated. PATIENTS AND METHODS: Cosmetic results in 47 patients having a per-operative implant were compared to 123 patients having a delayed interstitial implant in a matched case-control study. Cosmesis was scored on a four-point-scale varying from 0 (excellent) to 3 (poor). RESULTS: After mean follow-up of 63 months, three observers found no difference in cosmetic outcome between the two groups after adjustment for variables found to be related with cosmesis (difference in mean score 0.50, P=0.26). Implant volume at 100% isodose was not found to differ (P=0.084) between the per-operative group (mean 102 cm3, S.D. 34 cm3) and the delayed group (mean 93 cm3, S.D. 29 cm3). CONCLUSIONS: Performing per-operative implants has not led to smaller implants. The method of performing brachytherapy does not result in marked differences in cosmetic outcome. 相似文献
17.
Engelen MP Schols AM Does JD Wouters EF 《The American journal of clinical nutrition》2000,71(3):733-738
BACKGROUND: Skeletal muscle weakness is a prominent problem in many patients with chronic obstructive pulmonary disease (COPD). OBJECTIVE: The aim of the study was to determine the relation between skeletal muscle function, body composition, and lung function in COPD (emphysema and chronic bronchitis) patients and healthy volunteers. DESIGN: In 50 patients with chronic bronchitis, 49 patients with emphysema, and 28 healthy volunteers, skeletal muscle function was assessed by handgrip and linear isokinetic dynamometry. Whole-body and subregional fat-free mass (FFM) were assessed by dual-energy X-ray absorptiometry. RESULTS: Whole-body and extremity FFM were significantly lower in patients with emphysema (P < 0.001) and chronic bronchitis (P < 0.05) than in healthy volunteers, but trunk FFM was significantly lower only in patients with emphysema (P < 0.001). Extremity FFM was not significantly different between the COPD subtype groups, despite significantly lower values for whole-body and trunk FFM (P < 0.05) in patients with emphysema. Absolute skeletal muscle function (P < 0. 001) and muscle function per kilogram of whole-body FFM were significantly lower in both COPD subtype groups than in healthy volunteers (P < 0.05), but no significant difference was found between patients with chronic bronchitis and those with emphysema. Muscle function per kilogram of extremity FFM was not significantly different between the 3 groups and was not associated with forced expiratory volume in 1 s. CONCLUSION: Skeletal muscle weakness is associated with wasting of extremity FFM in COPD patients, independent of airflow obstruction and COPD subtype. 相似文献
18.
J A Langendijk M K Tjwa J M de Jong G P ten Velde E F Wouters 《Radiotherapy and oncology》1998,49(2):175-183
BACKGROUND AND PURPOSE: This retrospective study was conducted to investigate whether endobronchial brachytherapy (EBB) is a risk factor for massive haemoptysis in patients primarily treated by a combination of EBB and external irradiation (XRT) for NSCLC. MATERIALS AND METHODS: The records of 938 patients with inoperable NSCLC who were treated with XRT and/or EBB were reviewed. The patients were divided into five groups as follows: group XRT, treated by XRT alone (n = 421); group XRTelig, treated by XRT but eligible for EBB (n = 419); group XRTEBB, primarily treated with EBB+XRT (n = 62); group EBBrec, treated by EBB for recurrence after XRT (n = 23); and group EBB, treated by EBB alone (n = 13). EBB was delivered using HDR. Patients with bronchoscopy-proven endobronchial tumour in the proximal airways, i.e. the trachea, the main bronchus or lobar bronchus were considered eligible for EBB. RESULTS: One hundred one out of 938 patients (10.8%) died from massive haemoptysis. The incidence was 4.3% in group XRT, 13.1% in group XRTelig and 25.4% in group XRTEBB. The differences between groups XRT and XRTelig as well as between groups XRTelig and XRTEBB were statistically significant (P<0.01). The incidence of massive haemoptysis depended significantly on the fraction size of brachytherapy. When two fractions of 7.5 Gy or a single fraction of 10 Gy were used, 11.1% of the patients died from massive haemoptysis. However, when a single dose of 15 Gy was used, 47.8% died from massive haemoptysis. In the multivariate analysis, a single dose of 15 Gy EBB was the most important prognostic factor for massive haemoptysis. CONCLUSION: XRT+EBB as primary treatment for NSCLC does not lead to a higher risk of massive haemoptysis as compared to XRT alone when fraction sizes for EBB of 7.5 or 10 Gy are used. However, the risk of massive haemoptysis increases dramatically when a fraction size of 15 Gy is used. 相似文献
19.
Dirk De Ruysscher Stofferinus Wanders Andre Minken Aniek Lumens Jacqueline Schiffelers Cissie Stultiens Serve Halders Liesbeth Boersma Angela van Baardwijk Tom Verschueren Monique Hochstenbag Gabriel Snoep Brad Wouters Sebastiaan Nijsten S?ren M Bentzen Marinus van Kroonenburgh Michel Ollers Philippe Lambin 《Radiotherapy and oncology》2005,77(1):5-10
BACKGROUND AND PURPOSE: To investigate the effect of radiotherapy planning with a dedicated combined PET-CT simulator of patients with locally advanced non-small cell lung cancer. PATIENTS AND METHODS: Twenty-one patients underwent a pre-treatment simulation on a dedicated hybrid PET-CT-simulator. For each patient, two 3D conformal treatment plans were made: one with a CT based PTV and one with a PET-CT based PTV, both to deliver 60Gy in 30 fractions. The maximum tolerable prescribed radiation dose for CT versus PET-CT PTV was calculated based on constraints for the lung, the oesophagus, and the spinal cord, and the Tumour Control Probability (TCP) was estimated. RESULTS: For the same toxicity levels of the lung, oesophagus and spinal cord, the dose could be increased from 55.2+/-2.0Gy with CT planning to 68.9+/-3.3Gy with the use of PET-CT (P=0.002), with corresponding TCP's of 6.3+/-1.5% for CT and 24.0+/-5.6% for PET-CT planning (P=0.01). CONCLUSIONS: The use of a combined dedicated PET-CT-simulator reduced radiation exposure of the oesophagus and the lung, and thus allowed significant radiation dose escalation whilst respecting all relevant normal tissue constraints. 相似文献
20.