| 1. |
- Borg, A, et al.
(författare)
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Prognostic significance of p53 overexpression in primary breast cancer : a novel luminometric immunoassay applicable on steroid receptor cytosols.
- 1995
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 71:5, s. 1013-1017
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Tidskriftsartikel (refereegranskat)abstract
- A novel quantitative luminometric immunoassay (LIA) has been developed for the measurement of wild-type and mutant p53 protein in extracts from breast tumour tissue. The LIA was found to yield reliable estimates of p53 expression in cytosol samples routinely prepared for steroid receptor analysis as compared with results obtained with immunohistochemical analysis. The LIA was evaluated on 205 primary breast tumour cytosols prepared for steroid receptor analysis and stored frozen at -80 degrees C for 6-8 years, p53 protein being detected in 65% of the samples (range 0.01-23 ng mg-1 protein). Using an arbitrary cut-off value of 0.15 ng mg-1 protein, 30% of the tumours were classified as manifesting p53 overexpression. Significant and independent correlations were found to exist between p53 overexpression and shorter disease-free (P < 0.001) and overall survival (P = 0.039) at a median duration of follow-up of 50 months. p53 overexpression was related to low oestrogen receptor content and high proliferation rate (S-phase fraction). No relationship was found to tumour size or the presence of lymph node metastasis. Three tumours possessed an extremely high p53 content (> 10 ng mg-1 protein), all of which were of medullary or high-grade ductal type, oestrogen and progesterone receptor negative, DNA non-diploid, had S-phase fractions of > 22% and recurred within 1-2 years. In summary, a new sensitive and quantitative LIA suitable for routine analysis of p53 protein in steroid receptor cytosol preparations from breast tumours has been developed to confirm the prognostic importance of p53 protein accumulation in human breast cancer.
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| 2. |
- Lane, G. J., et al.
(författare)
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Identification of excited states in doubly odd [Formula Presented]Sb : Smooth band termination
- 1997
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Ingår i: Physical Review C - Nuclear Physics. - 0556-2813. ; 55:5, s. 2127-2131
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Tidskriftsartikel (refereegranskat)abstract
- Excited states in [Formula Presented]Sb have been identified for the first time in a series of [Formula Presented]-spectroscopy experiments using both thin and backed targets, including neutron-fold and recoil-mass measurements to provide unambiguous channel identification. The three decoupled intruder bands observed in [Formula Presented]Sb are based upon configurations involving 2p-2h excitations across the [Formula Presented] shell gap and show the features of smooth band termination. The yrast intruder band, which has been connected to the low-spin levels, is tentatively identified up to its predicted termination at [Formula Presented]. Excellent agreement with configuration-dependent cranked Nilsson-Strutinsky calculations is obtained for the high-spin states near termination.
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| 3. |
- Simmonds, R E, et al.
(författare)
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Clarification of the risk for venous thrombosis associated with hereditary protein S deficiency by investigation of a large kindred with a characterized gene defect
- 1998
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Ingår i: Annals of Internal Medicine. - : American College of Physicians. - 0003-4819. ; 128:1, s. 8-14
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Protein S is an important regulatory protein of the coagulation cascade. The risk for venous thrombosis associated with protein S deficiency has been uncertain because all previous risk estimates used phenotypic evaluation alone, which can be ambiguous.OBJECTIVE: To quantitate the risk for thrombosis associated with a characterized protein S gene mutation that causes a Gly295-->Val substitution and protein S deficiency.DESIGN: Retrospective study of a single extended family.SETTING: University hospital referral center.PARTICIPANTS: A 122-member protein S-deficient family, in which 44 members had a recently characterized gene defect.MEASUREMENTS: Comprehensive history of thrombosis, history of exposure to acquired risk factors for thrombosis, levels of total and free protein S antigen, and genotype for the mutation causing the Gly295-->Val substitution.RESULTS: Kaplan-Meier analysis of thrombosis-free survival showed that the probability of remaining free of thrombosis at 30 years of age is 0.5 (95% CI, 0.33 to 0.66) for carriers of the Gly295-->Val mutation compared with 0.97 (CI, 0.93 to 1.0) for normal family members (P < 0.001). In a multivariate Cox regression model that included smoking and obesity, the mutation was a strong independent risk factor for thrombosis (hazard ratio, 11.5 [CI, 4.33 to 30.6]; P < 0.001). For free (but not total) protein S antigen levels, the distributions of persons with and persons without the mutation did not overlap.CONCLUSIONS: Protein S deficiency, as defined by the presence of a causative gene mutation or a reduced level of free protein S antigen, is a strong independent risk factor for venous thrombosis in a clinical affected family.
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| 4. |
- Simmonds, Rachel E., et al.
(författare)
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Genetic and phenotypic analysis of a large (122-member) protein S-deficient kindred provides an explanation for the familial coexistence of type I and type III plasma phenotypes
- 1997
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Ingår i: Blood. - 0006-4971. ; 89:12, s. 4364-4370
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Tidskriftsartikel (refereegranskat)abstract
- Protein S deficiency is a known risk factor for thrombosis. The coexistence of phenotypic type I (reduction in total and free antigen) and type III (reduction in free antigen only) protein S deficiencies in 14 of 18 families was recently reported. We investigated the cause of this phenotypic variation in the largest of these families (122 family members, including 44 affected individuals) using both molecular genetic and phenotypic analysis. We have identified a sole causative mutation (Gly295Val) in three family members representative of the variable phenotype. Complete cosegregation of the mutation with reduced free protein S antigen levels was found, regardless of the total antigen level. Analysis of phenotypic data showed high correlations between total protein S antigen and age in both normal and protein S-deficient family members, irrespective of gender. Free protein S antigen levels were not influenced by age, a finding explained by an association between beta-chain containing C4b-binding protein (C4bBP-beta+) antigen levels and age. We propose that the identified Gly295Val mutation causes quantitative, or type I, protein S deficiency, and that as age increases the total protein S antigen level normalizes with respect to the reference plasma pool, giving rise to a type III protein S-deficient phenotype.
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