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101.
Sevilla C Moatti JP Julian-Reynier C Eisinger F Stoppa-Lyonnet D Bressac-de Paillerets B Sobol H 《European journal of human genetics : EJHG》2002,10(10):599-606
Breast carcinoma is the most common type of cancer affecting women in the Western world. The hereditary forms, which amount from 5 to 10% of all the cases of breast cancer, mainly involve BRCA1 or BRCA2 mutations. Due to the diagnostic strategy used by the patent owner, Direct DNA sequencing (DS) may become the only BRCA1/2 test procedure available, although there exist several alternative strategies. A cost-effectiveness study was carried out using BRCA1 testing as a model. The main techniques available for performing mutation searches were assessed: DS, denaturing high performance liquid chromatography (DHPLC), single-strand conformation polymorphism (SSCP), denaturing gradient gel electrophoresis (DGGE), heteroduplex analysis (HA), fluorescent assisted mismatch analysis (FAMA) and the protein truncation test (PTT). Twenty strategies involving the use of one or more techniques were then devised for performing the complete genetic analysis. DS was adopted as the 'gold standard' for effectiveness. All the strategies except for DS involved a two-step procedure. The first step consisted of pre-screening the 22 coding exons of BRCA1. The second step consisted of performing DS only on the variations detected in the coding sequence. The cost of the strategies tested, including a pre-screening stage, turned out to be 30 to 90% lower than that of DS, whatever annual use was made of the equipment. The most cost-effective strategy, ie, that corresponding to the lowest cost per mutation detected, was found to be a combination between PTT on exon 11 (60% of the coding sequence) and HA on the remaining 21 exons (PTT(11)+ HA(21)). However, since a high false negative rate is associated with this strategy, at least four other strategies are worth mentioning: PTT(11)+ DHPLC(21), DHPLC alone, FAMA(11)+ DHPLC(21) and FAMA alone. Our results on genetic testing for breast cancer show that DS is not the most cost-effective method available. The monopolist approach of the firm which owns the patents on the BRCA1/2 genes, may, therefore limit the use of the most cost-effective strategies. 相似文献
102.
Massimiliano Valeriani Domenico Restuccia Vincenzo Di Lazzaro Domenica Le Pera Carmen Barba Pietro Tonali François Mauguiere 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1998,120(3):306-315
Brain electrical source analysis (BESA) of the scalp electroencephalographic activity is well adapted to distinguish neighbouring
cerebral generators precisely. Therefore, we performed dipolar source modelling in scalp medium nerve somatosensory evoked
potentials (SEPs) recorded at 1.5-Hz stimulation rate, where all the early components should be identifiable. We built a four-dipole
model, which was issued from the grand average, and applied it also to recordings from single individuals. Our model included
a dipole at the base of the skull and three other perirolandic dipoles. The first of the latter dipoles was tangentially oriented
and was active at the same latencies as the N20/P20 potential and, with opposite polarity, the P24/N24 response. The second
perirolandic dipole showed an initial peak of activity slightly earlier than that of the N20/P20 dipolar source and, later,
it was active at the same latency as the central P22 potential. Lastly, the third perirolandic dipole exaplaining the fronto-central
N30 potential scalp distribution was constantly more posterior than the first one. In order to evaluate the effect of an increasing
repetition frequency on the activity of SEP dipolar sources, we applied the model built from 1.5-Hz SEPs to traces recorded
at 3-Hz and 10-Hz repetition rates. We found that the 10-Hz stimulus frequency reduced selectively the later of the two activity
phases of the first perirolandic dipole. The decrement in strength of this dipolar source can be explained if we assume that:
(a) the later activity of the first perirolandic dipole can represent the inhibitory phase of a “primary response”; (b) two
different clusters of cells generate the opposite activities of the tangential perirolandic dipole. An additional finding
in our model was that two different perirolandic dipoles contribute to the centro-parietal N20 potential generation.
Received: 5 August 1997 / Accepted: 26 November 1997 相似文献
103.
Pierre Zachary Murielle Ullmann Saadi Djeddi Nicolas Meyer Marie-Josée Wendling Evelyne Schvoerer Fran?oise Stoll-Keller Jean-Pierre Gut 《Journal of clinical virology》2005,34(3):207-10; discussion 216-8
BACKGROUND: Most studies evaluating antibody detection assays are conducted on samples from healthy blood donors but not on samples of hospitalized patients which can show non-specific reactions. OBJECTIVES: To compare the performance of three commercial automated assays for the detection of hepatitis C virus (HCV) antibodies, Monolisa anti-HCV Plus version 2, Axsym anti-HCV 3.0 and Vitros anti-HCV, on a population of hospitalized patients. STUDY DESIGN: The specificity of the assays was prospectively evaluated in 2020 routine serum samples. In order to assign the serostatus of each sample, those giving positive or discordant results were further tested by three immunoblots and by RT-PCR (Roche). Moreover, the sensitivity was evaluated on eight commercial HCV seroconversion panels. RESULTS: The Monolisa, Axsym and Vitros assays showed specificities of 99.64%, 99.12% and 99.33%, respectively. Concerning the sensitivity, among 49 samples, the number of positive results was 21, 24 and 24 for the Monolisa, Axsym and Vitros kits, respectively. The differences were not statistically significant at an alpha risk of 5%. CONCLUSIONS: All assays appeared to be reliable for routine screening, but there were a surprising number of indeterminate samples that could not be resolved by confirmatory tests. 相似文献
104.
Clinical evidence of the nonpathogenic nature of the M34T variant in the connexin 26 gene 总被引:2,自引:0,他引:2
Feldmann D Denoyelle F Loundon N Weil D Garabedian EN Couderc R Joannard A Schmerber S Delobel B Leman J Journel H Catros H Ferrec C Drouin-Garraud V Obstoy MF Moati L Petit C Marlin S 《European journal of human genetics : EJHG》2004,12(4):279-284
Mutations in GJB2 are the most common cause of congenital nonsyndromic hearing loss. The controversial allele variant M34T has been hypothesized to cause autosomal dominant or recessive nonsyndromic hearing impairment and some in vitro data has been consistent with this hypothesis. In this report, we present the clinical and genotypic study of 11 families (seven familial forms of nonsyndromic sensorineural hearing loss (NSSNHL) and four sporadic cases) in which the M34T GJB2 variant has been identified. The M34T mutation did not segregate with the deafness in six of the seven familial forms of NSSNH. Eight persons with normal audiogram presented a heterozygous M34T variation and five normal hearing individuals were composite heterozygous for M34T and another GJB2 mutation. Four normal hearing individuals with a documented audiogram were M34T/35delG and one was M34T/(GJB6-D13S1830)del. Screening a French control population of 116 subjects we have found an M34T allele frequency of 1.72%. This percentage was not significatively different from the prevalence of the M34T allele in the deaf population, which was 2.12%. All these data suggest that the M34T variant is not clinically significant in human and is a frequent polymorphism in France. 相似文献
105.
106.
Prediction of AVM obliteration after stereotactic radiotherapy using radiobiological modelling 总被引:1,自引:0,他引:1
Mavroidis P Theodorou K Lefkopoulos D Nataf F Schlienger M Karlsson B Lax I Kappas C Lind BK Brahme A 《Physics in medicine and biology》2002,47(14):2471-2494
This study was carried out in order to derive the radiobiological parameters of the dose-response relation for the obliteration of arteriovenous malformation (AVM) following single fraction stereotactic radiotherapy. Furthermore, the accuracy by which the linear Poisson model predicts the probability of obliteration and how the haemorrhage history, location and volume of the AVM influence its radiosensitivity are investigated. The study patient material consists of 85 patients who received radiation for AVM therapy. Radiation-induced AVM obliterations were assessed on the basis of post-irradiation angiographies and other radiological findings. For each patient the dose delivered to the clinical target volume and the clinical treatment outcome were available. These data were used in a maximum likelihood analysis to calculate the best estimates of the parameters of the linear Poisson model. The uncertainties of these parameters were also calculated and their individual influence on the dose-response curve was studied. AVM radiosensitivity was assumed to be the same for all the patients. The radiobiological model used was proved suitable for predicting the treatment outcome pattern of the studied patient material. The radiobiological parameters of the model were calculated for different AVM locations, bleeding histories and AVM sizes. The range of parameter variability had considerable effect on the dose-response curve of AVM. The correlation between the dosimetric data and their corresponding clinical effect could be accurately modelled using the linear Poisson model. The derived response parameters can be introduced into the clinical routine with the calculated accuracy assuming the same methodology in target definition and delineation. The known volume dependence of AVM radiosensitivity was confirmed. Moreover, a trend relating AVM location with its radiosensitivity was observed. 相似文献
107.
Reciprocal translocations in breast tumor cell lines: cloning of a t(3;20) that targets the FHIT gene 总被引:1,自引:0,他引:1
108.
Expression and folding of an antibody fragment selected in vivo for high expression levels in Escherichia coli cytoplasm 总被引:1,自引:0,他引:1
Laden JC Philibert P Torreilles F Pugnière M Martineau P 《Research in microbiology》2002,153(7):469-474
In this review, we summarize some of our results on folding and directed evolution of an antibody fragment in Escherichia coli cytoplasm. We will also discuss some attempts to construct other antibodies active in this cellular compartment. 相似文献
109.
Cloning,sequencing and analysis of the yeastS. uvarum ERG10 gene encoding acetoacetyl CoA thiolase 总被引:7,自引:0,他引:7
Sylvie Dequin Remi Gloeckler Christopher J. Herberte Françoise Boutelet 《Current genetics》1988,13(6):471-478
Summary TheERG10 gene specific toS. uvarum, a brewing yeast, has been cloned by complementation of anS. cerevisiae erg10 mutant.S. uvarum contains two differentERG10 genes. One of these is similar to theS. cerevisiae ERG10 gene; they are structurally different, but functionally homologous. The clonedERG10 gene has been located on chromosome XVI, and we have shown that it is allelic to the previously isolatedtsm0115 mutants. Northern blot and sequence analysis indicate that theERG10 gene is highly expressed, and biochemical and genetic evidence show that it encodes the cytoplasmic acetoacetyl CoA thiolase. 相似文献
110.
de Tychey C Spitz E Briançon S Lighezzolo J Girvan F Rosati A Thockler A Vincent S 《Journal of affective disorders》2005,85(3):323-326
BACKGROUND: The assessment of perinatal depressions and coping style. Methods: With depression scales (EPDS, GHQ.12) and Carver's BriefCope, the authors compared the prevalence rates of pre and postnatal depression in a cohort of 277 French women. RESULTS: Their work revealed very high levels of prenatal depression (almost 20%) and less important but nonetheless sizeable rates (11%) of postnatal depression, making such perinatal depressions a major public health concern. The coping styles proposed in Carver's public health BriefCope questionnaire make it possible to significantly differentiate during these two periods between depressive women and their non-depressed counterparts. CONCLUSIONS: This enables us to underline factors of risk and protection suggesting the importance of setting up compensatory and preventive systems and evaluating their pertinence in the framework of future research. 相似文献