1,721,057 research outputs found
TRENDS IN PHARMACOGENOMICS OF DRUGS USED IN THE TREATMENT OF ASTHMA
No full textPharmacogenetic studies of drugs used in the treatment of asthma have produced a few examples of reduced response in patients carrying specific genotypes in genes involved in the action of beta-2 agonists or leukotriene modifiers. Other candidate genes related to these drugs, as well as glucocorticoids, theophilline, anticholinergics, antihistaminics, and drug-metabolizing enzymes, may be proposed. Statistical power and population stratification may be issues of importance in case-control association studies. Future developments include expanded gene knowledge from asthma genetic and genomic studies, the development of new preventive and curative treatments, multiple contemporary genotyping methods for pharmacogenetically important genes in a given individual, and the construction of asthma functional pharmacogenomic profiles. In conclusion, it seems that asthma pharmacogenetic studies need to be replicated in prospective clinical trials in different populations with a large number of subjects being genotyped. It is suggested that large clinical trials which are proposed for asthma drugs experimentation should include a pharmacogenetic study as well. © 2003 Elsevier Ltd. All rights reserved
Cistic Fibrosis mutation testing in Italy.
No full textIn Italy, Cystic fibrosis (CF) mutation frequency differences have been observed in different regions. In the northeastern Veneto and Trentino Alto Adige regions, a complete cystic fibrosis transmembrane conductance regulator (CFTR) gene screening in CF patients detected through a newborn screening program has identified about 90% of the mutations. In these two regions, the current detection rate using a CF screening panel containing the 16 most common mutations is 86.6%. CF mutations in some other Italian regions have not been so thoroughly analysed. Available data indicate that a more general national screening panel comprising 31 mutations may detect about 75 % of all CF mutations in Italy
Herpes simplex virus replication in the presence of DNA polymerase alpha inhibitors
No full text2-(p-n-butylanilino)deoxyadenosine (BuAdA), and N-2-(p-n-butylphenyl)deoxyguanosine (BuPdG), selective inhibitors of mammalian DNA polymerase alpha, were added to BHK-21(C13) cell cultures infected with herpes simplex virus type 1 (HSV-1) strain 17 syn +. Infectious virus production decreased significantly in the presence of the inhibitor at concentrations varying from 1 nM to 100 microM. BuPdG was more effective than BuAdA at all concentrations tested, while it inhibited virus yield as much as BuAdA when CVG2, a thymidine kinase deficient (TK-) HSV-1, was employed. HSV DNA synthesis, determined by quantitation of CsCl separated DNA peaks, was inhibited by each compound. BuPdG inhibited viral DNA replication more than BuAdA, while the effect on cell DNA synthesis was the same as that of BuAdA. CVG2 DNA replication was inhibited to the same level by BuAdA as by BuPdG. These results indicate that HSV DNA replication is partially dependent on cell DNA polymerase alpha activity, and that the greater effect of BuPdG on viral replication may be ascribed to its action on HSV thymidine kinase
Serotonin binding proteins from human blood platelets. An experimental model system for studies on properties of synaptic vesicles
No full textSerotonin uptake, binding and release were studied in human blood platelets. The uptake showed marked individual differences while the loss of 5-HT during resuspension of the 5-HT loaded platelets was constant. The existence of 5-HT binding proteins was demonstrated by equilibrium dialysis, gel filtration on a column equilibrated with 5-HT, affinity chromatography on a 5-HT-Sepharose column and polyacryl-amide disc gel electrophoresis experiments. After incubation of the platelet extract in the presence of [14-C]5-HT, electrophoretic and autoradiographic analysis demonstrated the presence of three 5-HT binding proteins, two of which were soluble glycoproteins specific for serotonin
Genetics of idiopathic disseminated bronchiectasis
No full textBronchiectasis is an abnormal dilation of bronchi, consequent to the destruction of their walls. It is included in the category of obstructive pulmonary diseases, along with chronic obstructive pulmonary disease (COPD), asthma, and cystic fibrosis. In approximately 50% of cases, bronchiectasis is associated with underlying conditions; in the remainder, known causes are not ascertainable (idiopathic bronchiectasis). A search for genetic determinants of this phenotype, with the cystic fibrosis gene as a candidate, has been performed by three independent groups. The results of this search agreed on the association of bronchiectasis with cystic fibrosis gene mutations and polymorphisms. The cystic fibrosis gene is also associated with bronchiectasis due to rheumatoid arthritis and allergic bronchopulmonary aspergillosis. A few other genes have been investigated in idiopathic bronchiectasis, with negative results. Idiopathic bronchiectasis is, therefore, to be considered as an obstructive multifactorial disorder belonging to the category of cystic fibrosis monosymptomatic diseases (or CFTR-opathies), whose pathogenesis is influenced by environmental factors and other undetermined genes
Haplotype analysis of collagen type I genes in the general population and in osteogenesis imperfecta families.
No full textThe allele frequencies of 2 new polymorphic markers of collagen type I proalpha 1 (COL1A1) and proalpha 2 (COL1A2) genes were determined in a random sample of chromosomes by polymerase chain reaction. The minor allele frequencies were 0.27 for COL1A1/+88Mn1I, and 0.39 for COL1A2/1446 PvuII RFLPs, respectively. These 2 polymorphisms increased the combined (PIC) values we previously determined in the Italian population with Southern blotting procedures, from 0.71 at the COL1A1 locus to 0.81, and from 0.73 at the COL1A2 locus to 0.88, respectively. With a combination of these markers, we have carried out the segregation analysis of 4 new families in which osteogenesis imperfecta (OI) segregated as a dominant trait. The disease segregated with COL1A1 in 2 OI type I families, and with COL1A2 in one OI type IV family. In one OI type I family the concordant locus was uncertain. This analysis was extended to the 7 dominant OI families we previously reported: in 3 out of 11 pedigrees either loc..
A common polymorphism in exon 46 of the human autosomal dominant polycystic kidney disease 1 gene (PKD1)
No full textAutosomal dominant polycystic kidney disease (ADPKD) is one of the most common single gene diseases in humans. We have identified a synonymous T to C transition polymorphism in exon 46 of the PKD1 gene (12838T-->C, Pro4209Pro). The polymorphism was present with similar frequencies in ADPKD patients and unaffected individuals. The heterozygosity, determined in 89 Italian individuals, was 0.347. The frequency of the rarer allele was 0.222. This polymorphism is easy to determine as it abolishes a naturally occurring Ddel restriction site. The availability of an additional intragenic marker in the PKD1 gene will improve the accuracy of linkage studies in ADPKD families
Complete mutational screening of the CFTR gene in 120 patients with pulmonary disease.
No full textIn order to determine the possible role of the cystic fibrosis transmembrane regulator (CFTR) gene in pulmonary diseases not due to cystic fibrosis, a complete screening of the CFTR gene was performed in 120 Italian patients with disseminated bronchiectasis of unknown cause (DBE), chronic bronchitis (CB), pulmonary emphy sema (E), lung cancer (LC), sarcoidosis (S) and other forms of pulmonary disease. The 27 exons of the CFTR gene and their intronic flanking regions were analyzed by denaturing gradient gel electrophoresis and automatic sequencing. Mutations were detected in 11/23 DBE (P = 0.009), 7/25 E, 5/27 CB, 5/26 LC, 5/8 S (P = 0.013), 1/4 tuberculosis, and 1/5 pneumonia patients, and in 5/33 controls. Moreover, the IVS8-5T allele was detected in 6/25 E patients (P = 0.038). Four new mutations were identified: D651N, 2377C/T, E826K, and P1072L. These results confirm the involvement of the CFTR gene in disseminated bronchiectasis of unknown origin, and suggest a possible role for CFTR gene mutations in sarcoidosis, and for the 5T allele in pulmonary emphysema
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