1,721,021 research outputs found
Determination of the frequency of the common 657Del5 Nijmegen breakage syndrome mutation in the German population: no association with risk of breast cancer
No full textNijmegen breakage syndrome (NBS) is an autosomal recessive chromosomal instability syndrome characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition. It shares a number of features with the Ataxia telangiectasia (AT) syndrome: the most notable are high sensitivity to ionizing radiation and predisposition to cancer. Recently, the gene responsible for NBS has been identified on chromosome band 8q21. It encodes a DNA double-strand break repair protein, named Nibrin. A truncating 5-bp deletion (657Del5) has been identified in 90% of NBS patients and this is presumed to be of Slavic origin. There is evidence that heterozygous AT mutation carriers are predisposed to breast cancer. Since the NBS phenotype at the cellular level is very similar to AT, we have screened 477 German breast cancer patients, aged under 51 years, and 866 matched controls for the common NBS mutation. We have identified one carrier among the cases and one among the controls, indicating that the population frequency of this NBS mutation is 1 in 866 people (95% CI = 1 in 34,376 to 1 in 156) and the estimated prevalence of NBS is thus 1 in 3 million people. The proportion of breast cancer attributable to this mutation is less than 1%
Comparison of DNA repair protein expression and activities between human fibroblast cell lines with different radiosensitivities
No full textIn order to investigate the molecular basis of variation in response to ionising radiation (IR) in radiotherapy patients, we have studied the expression of several genes involved in DNA double-strand break repair pathways in fibroblast cell lines. Ten lines were established from skin biopsies of cancer patients with different normal-tissue reactions to IR, and 3 from a control individual. For all 10 test cell lines, the cellular radiosensitivity was also known. Using Western blots we measured, in non-irradiated cells, the basal expression levels of ATM, Rad1 and Hus1, involved in the control of cellular DNA damage checkpoints, together with DNA-PKcs, Ku70, Ku80; XRCC4, ligaseIV and Rad51, involved in radiation- induced DSB repair. We also analysed the in vitro enzymatic activities, under non-irradiated conditions, of the DNA-PK and XRCC4/ligaseIV complexes. The levels of expression of the different proteins were similar in all the cell lines, but the activities of the DNA-PK and XRCC4/ligaseIV complexes showed some differences. These differences did not correlate with either the normal tissue response of the patient in vivo or with cellular radiation sensitivity in vitro. The activity differences of these enzyme complexes, therefore, do not account for the variation of responses seen between patients
BRCA1 and BRCA2 mutations in a population-based study of male breast cancer
No full textBackground: The contribution of BRCA1 and BRCA2 to the incidence of male breast cancer (MBC)
in the United Kingdom is not known, and the importance of these genes in the increased risk of female
breast cancer associated with a family history of breast cancer in a male first-degree relative is unclear.
Methods: We have carried out a population-based study of 94 MBC cases collected in the UK. We
screened genomic DNA for mutations in BRCA1 and BRCA2 and used family history data from these
cases to calculate the risk of breast cancer to female relatives of MBC cases. We also estimated the
contribution of BRCA1 and BRCA2 to this risk.
Results: Nineteen cases (20%) reported a first-degree relative with breast cancer, of whom seven also
had an affected second-degree relative. The breast cancer risk in female first-degree relatives was 2.4
times (95% confidence interval [CI] = 1.4–4.0) the risk in the general population. No BRCA1 mutation
carriers were identified and five cases were found to carry a mutation in BRCA2. Allowing for a
mutation detection sensitivity frequency of 70%, the carrier frequency for BRCA2 mutations was 8%
(95% CI = 3–19). All the mutation carriers had a family history of breast, ovarian, prostate or
pancreatic cancer. However, BRCA2 accounted for only 15% of the excess familial risk of breast
cancer in female first-degree relatives.
Conclusion: These data suggest that other genes that confer an increased risk for both female and
male breast cancer have yet to be found
Refined localization to contiguous regions on chromosome 10q of the two genes (H4 and RET) that form the oncogenic sequence PTC
No full textIn this report we confirm the localization of the human RET proto-oncogene to chromosome 10q11.2, both by Southern blot analysis of a panel of human-rodent somatic cell hybrids and by in situ hybridization on human metaphase chromosomes. Previously, we had assigned to the same chromosome region the gene termed H4. In about 25% of papillary thyroid carcinomas, this gene was shown to rearrange with RET to give rise to the transforming sequence PTC. The analysis of different cell hybrids containing subfragments of chromosome 10, in conjunction with pulse field gel electrophoresis, established that H4 is mapped distally to RET at a distance not less than 280 kb. These findings suggest that intrachromosomal rearrangements are responsible for PTC activation in papillary thyroid carcinomas
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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