Search results for "Codon"
showing 10 items of 196 documents
Kirsten ras mutations in patients with colorectal cancer: the 'RASCAL II' study
2001
Researchers worldwide with information about the Kirsten ras (Ki-ras) tumour genotype and outcome of patients with colorectal cancer were invited to provide that data in a schematized format for inclusion in a collaborative database called RASCAL (The Kirsten ras in-colorectal-cancer collaborative group). Our results from 2721 such patients have been presented previously and for the first time in any common cancer, showed conclusively that different gene mutations have different impacts on outcome, even when the mutations occur at the same site on the genome. To explore the effect of Ki-ras mutations at different stages of colorectal cancer, more patients were recruited to the database, whi…
Specific TP53 and/or Ki-ras mutations as independent predictors of clinical outcome in sporadic colorectal adenocarcinomas: results of a 5-year Grupp…
2005
BACKGROUND: Although Ki-ras and TP53 mutations have probably been the genetic abnormalities most exhaustively implicated and studied in colorectal cancer (CRC) progression, their significance in terms of disease relapse and overall survival has not yet clearly been established. PATIENTS AND METHODS: A prospective study was carried out on paired tumor and normal colon tissue samples from a consecutive series of 160 previously-untreated patients, undergoing resective surgery for primary operable sporadic CRC. Mutations within the TP53 (exons 5-8) and Ki-ras (exon 2) genes were detected by PCR-SSCP analyses following sequencing. RESULTS: Mutation analyses of exons 5 to 8 of the TP53 gene showe…
Risk Profiles and Penetrance Estimations in Multiple Endocrine Neoplasia Type 2A Caused by Germline RET Mutations Located in Exon 10
2010
Multiple endocrine neoplasia type 2 is characterized by germline mutations in RET. For exon 10, comprehensive molecular and corresponding phenotypic data are scarce. The International RET Exon 10 Consortium, comprising 27 centers from 15 countries, analyzed patients with RET exon 10 mutations for clinical-risk profiles. Presentation, age-dependent penetrance, and stage at presentation of medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism were studied. A total of 340 subjects from 103 families, age 4-86, were registered. There were 21 distinct single nucleotide germline mutations located in codons 609 (45 subjects), 611 (50), 618 (94), and 620 (151). MTC was present…
The use of high doses of oxycodone in an acute palliative care unit.
2010
A retrospective study of patients who were prescribed controlled-release oxycodone (CRO) in a period of 3 years (2006-2008) was performed. A total of 212 patients were prescribed at discharge CRO for background analgesia; 129, 43, and 40 patients were prescribed doses of oxycodone of less than 120 mg/day (group L), 120 to 240 mg/day (group M), and more than 240 mg/day (group L), respectively. No differences in gender, primary diagnosis, and pain mechanisms were found, but doses were significantly lower in older patients (P < .0005). At discharge, adverse effects were mild and only a minority of patients were switched to other opioids. This study demonstrated that CRO administered in lar…
A European family with histidine 58 transthyretin mutation in familial amyloid polyneuropathy
1997
1. IntroductionMore than 50 mutations of the transthyretin (TTR) [1]molecule resulting in different clinical forms of amyloidosisincluding familial amyloid polyneuropathy (FAP) havebeen reported to date. Within this FAP spectrum severaltransthyretin mutations are more frequent, others are rare.One mutation, the codon 58 histidine for leucine has pre-viously been recorded only in American subjects (Mary-land/German type), originally reported in a large kinship[2,3] and in another family from Ohio [4]. In the originaldescription of the Maryland/German type of amyloidosis[2], it was stated that the early immigrants in this pedigreewere from the Rhine river area, "nearly all of them from thelef…
Heterozygous nonsense SCN5A mutation W822X explains a simultaneous sudden infant death syndrome.
2008
The sudden, unexpected, and unexplained death of both members of a set of healthy twins (simultaneous sudden infant death syndrome (SSIDS)) is defined as a case in which both infants meet the definition of sudden infant death syndrome individually. A search of the world medical literature resulted in only 42 reported cases of SSIDS. We report the case of a pair of identical, male, monozygotic twins, 138 days old, who suddenly died, meeting the full criteria of SSIDS and where a genetic screen was performed, resulting in a heterozygous nonsense SCN5A mutation (W822X) in both twins. Immunohistochemistry was performed on cardiac tissue samples utilizing polyclonal antibodies anti-Na+ CP type V…
Sequence variation in couch potato and its effects on life-history traits in a northern malt fly, Drosophila montana
2011
Abstract Couch potato ( cpo ) has previously been connected to reproductive diapause in several insect species including Drosophila melanogaster , where it has been suggested to provide a link between the insulin signalling pathway and the hormonal control of diapause. In the first part of the study we sequenced nearly 3.6 kb of this gene in a northern Drosophila species ( Drosophila montana ) with a robust photoperiodically determined diapause and found several types of polymorphisms along the sequenced area. We also found variation among five Drosophila virilis group species in the length of the 5th exon of cpo and in the site of the stop codon at the end of this exon. The second part of …
Natural and engineered carboxy-terminal variants: decreased secretion and gain-of-function result in asymptomatic coagulation factor VII deficiency.
2012
We report 2 asymptomatic homozygotes for the nonsense p.R462X mutation affecting the carboxy-terminus of coagulation factor VII (FVII, 466 aminoacids). FVII levels of 3-5% and 2.7 ± 0.4% were found in prothrombin time-based and activated factor X (FXa) generation assays with human thromboplastins. Noticeably, FVII antigen levels were barely detectable (0.7 ± 0.2%) which suggested a gain-of-function effect. This effect was more pronounced with bovine thromboplastin (4.8 ± 0.9%) and disappeared with rabbit thromboplastin (0.7 ± 0.2%). This suggests that the mutation influences tissue factor/FVII interactions. Whereas the recombinant rFVII-462X variant confirmed an increase in specific activit…
Molecular Basis of Hereditary C1q Deficiency
1998
Abstract Complete selective deficiencies of the complement component C1q are rare genetic disorders which are associated with recurrent infections and a high prevalence of lupus erythematosus-like symptoms. The improvements in molecular biology techniques have facilitated the analysis of such genetic defects to a great extend. To date the basis of C1q deficiencies from 13 families have been studied at the genetic level. In each case single base mutations leading to either termination codons, frame shift or amino acid exchanges were thought to be responsible for these defects as no other aberrations were found. In addition to DNA analysis, conventional immunochemical and biochemical methods …
A comparative evaluation of NB30, NB54 and PTC124 in translational read-through efficacy for treatment of an USH1C nonsense mutation
2012
Translational read-through-inducing drugs (TRIDs) promote read-through of nonsense mutations, placing them in the spotlight of current gene-based therapeutic research. Here, we compare for the first time the relative efficacies of new-generation aminoglycosides NB30, NB54 and the chemical compound PTC124 on retinal toxicity and read-through efficacy of a nonsense mutation in the USH1C gene, which encodes the scaffold protein harmonin. This mutation causes the human Usher syndrome, the most common form of inherited deaf-blindness. We quantify read-through efficacy of the TRIDs in cell culture and show the restoration of harmonin function. We do not observe significant differences in the read…