1,720,972 research outputs found
Multiplex genotyping of CYP3A4, CYP3A5, CYP2C9 and CYP2C19 SNPs using MALDI-TOF mass spectrometry
No full textBackground: Pharmacogenetics is the study of genetic variations that cause alterations in drug level, drug
response and adverse drug reactions. SNPs found in CYP450 genes have the greatest genetic influences
on interindividual variability in drug bioavailability. The polymorphic nature of these genes may modulate
several enzyme levels that affect individual responses to pharmacological treatment. Among them, CYP3A4,
CYP3A5, CYP2C9 and CYP2C19 isoforms of CYP450 enzymes are involved in the metabolism of many
commonly prescribed drugs. Aims: In this study, we would like to develop a CYP450 genotyping platform
that could lead a complete definition of a patient’s metabolic genotype in order to improve the clinical
outcome of some drug treatments. Materials & methods: We used matrix-assisted laser desorption/
ionization time-of-flight mass spectrometry (MALDI-TOF MS) (Sequenom®) to develop a SNP genotyping
method. Results: This MALDI-TOF-based multiplexing system allows the simultaneous and efficient
genotyping of a set of CYP450 gene polymorphisms. Conclusion: The multiple CYP450 gene testing achieved
with this application can be used to develop diagnostic tests to predict drug responses and clinical outcomes
Five mutations in the GABAA α6 gene 5′ flanking region are associated with a reduced basal and ethanol-induced α6 upregulation in mutated Sardinian alcohol non-preferring rats
No full textThe presence of four nucleotide changes and a three base-pair deletion in the GABAA α6-subunit promoter is described in Sardinian alcohol non-preferring rats, selectively bred for their ethanol aversion. These mutations are associated with the R100Q α6 intragenic mutation that was previously characterized in the same animals. The possibility that these mutated nucleotides alter the ethanol-induced upregulation of the α6 gene was investigated by measuring cerebellar α6 mRNA levels after a chronic ethanol liquid diet in sNP rat. Real-time quantitative PCR showed an increased α6 gene expression after ethanol ingestion in normal and mutated rats. However, lower amounts of α6 mRNA levels were detected both in control and in ethanol-treated sNP rats carrying the five promoter and the intragenic mutations in a homozygous state. Using the electromobility shift assay, specific DNA binding sites were found in cerebellar extracts of the α6 regions comprising the five mutations. These results suggest that one or more of the mutated binding sites that were found in the 5′ flanking α6 region may be a consensus sequence for regulatory factors which are responsible for both basal and ethanol-induced α6 gene expression. © 2005 Elsevier B.V. All rights reserved
La tecnologia degli high density array nello studio del profilo d’espressione dell’RNA messaggero nelle linee di ratti sP (Sardinian alcohol-preferring) ed sNP (Sardinian alcohol-no preferring)
No full textMolecular characterization of new polymorphisms at the beta2, alpha1, gamma2 GABA(A) receptor subunit genes associated to a rat nonpreferring ethanol phenotype
No full text
Five mutations in the GABAA α6 gene 5’ flanking region are associated with a reduced basal and ethanol-induced α6 upregulation in mutated Sardinian alcohol non-preferring rats
No full textHigh density array technology for the study of mRNA expression profile in the sp and snp rat lines
No full textGoing 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
- …
