Genetic polymorphism of CYP genes, alone or in combination, as a risk modifier of tobacco-related cancers.

Tobacco use is causally associated with cancers of the lung, larynx, mouth, esophagus, kidneys, urinary tract, and possibly, breast. Major classes of carcinogens present in tobacco and tobacco smoke are converted into DNA-reactive metabolites by cytochrome P450 (CYP)-related enzymes, several of which display genetic polymorphism. Individual susceptibility to cancer is likely to be modified by the genotype for enzymes involved in the activation or detoxification of carcinogens in tobacco and repair of DNA damage.

[Preanalytical errors on the determination of arterial O(2)-partial pressure and their impact on the AaDO(2)].

Objectives: The paO(2) and AaDO(2) are routinely measured for evaluating pulmonary gas exchange. The normal value of the AaDO(2) amounts 10 mmHg when breathing atmospheric air and is said to increase with rising FIO(2). This increase is discussed controversially.

[Pre-analytic errors in the determination of arterial O(2)-partial pressure under hyperoxic conditions].

Objective: A variety of influences reduce the validity of the measured oxygen partial pressure (paO(2)). Most errors occur when obtaining the blood sample and preparing it for analysis. Unfortunately, there is great controversy concerning the relevance and extent of these pre-analytic errors.

Acetylation status is associated with serological changes but not clinically significant disease in patients receiving procainamide.

Objective: Autoantibodies occur in the majority of patients receiving procainamide (PA) for more than one year. Slow acetylator status has been proposed to predispose to their development. We previously reported the results of serological evaluation of 52 asymptomatic patients receiving PA.

Genes for human arylamine N-acetyltransferases in relation to loss of the short arm of chromosome 8 in bladder cancer.

Polymorphisms of N-acetyltransferase type 2 (NAT2) conferring the slow acetylator phenotype have been linked to increased susceptibility to arylamine-induced bladder cancer in Caucasians. Genes for NAT2, the other NAT isozyme, NAT1, and a NAT pseudogene (NATP) are found on 8p22, a region displaying loss of heterozygosity, particularly in invasive bladder tumours. A restriction enzyme digestion map has defined the relative positions of the NAT genes to each other and to adjacent CpG islands.

Impact of adduct determination on the assessment of cancer susceptibility.

The characterization of genetic determinants for cancer susceptibility is important for understanding disease pathogenesis and for preventive measures. There is growing evidence that a group of predisposing polymorphic genes exists, such as those involved in carcinogen metabolism and repair, which may increase cancer in certain environmentally exposed subjects, even those exposed only to low levels of carcinogens. In developing preventive strategies, it is therefore necessary to identify these vulnerable members in our society, particularly those suffering from an unfortunate combination of high carcinogen exposure, cancer-predisposing genes and lack of protective (dietary) factors.

[Evaluation of lactate measurement in blood and plasma with biosensor technology: a comparison of methods].

Unlabelled: The introduction of biosensor technology for near bedside measurement of plasma lactate concentrations has been a promising step for critical care profiling. However, methodological drawbacks and relevant inaccuracy have been reported. With the advent of a new biosensor (Chiron Diagnostics) and a revised NOVA Biomedical device, accuracy was expected to be improved.

[Remifentanil-propofol anesthesia in vertebral disc operations: a comparison with desflurane-N2O inhalation anesthesia. Effect on hemodynamics and recovery].

Objective: To ascertain whether there is a difference between total intravenous anaesthesia with propofol (P) and remifentanil (R) and inhalational anaesthesia with desflurane (D) and nitrous oxide (N) with regard to haemodynamic reactions, recovery profile and postoperative analgesic demand in patients scheduled for elective microsurgical vertebral disc resection.

Methods: 50 patients (ASA I-II, 18-65 years) were randomly assigned to receive total intravenous anaesthesia with propofol and remifentanil or inhalational anaesthesia with desflurane and nitrous oxide. After standardised induction of anaesthesia in both groups (1 microgram.

Mapping AAC1, AAC2 and AACP, the genes for arylamine N-acetyltransferases, carcinogen metabolising enzymes on human chromosome 8p22, a region frequently deleted in tumours.

Arylamine N-acetyltransferases (NATs) are encoded at two loci on 8p22, a region subject to deletions in bladder tumours. The two functional genes (AAC1 and AAC2 alias NAT1 and NAT2) without introns in the coding region, encode enzymes which metabolise carcinogens, including bladder carcinogens. They are both multi-allelic and certain alleles have been implicated as susceptibility factors in bladder cancer.

Arylamine N-acetyltransferase in erythrocytes of cystic fibrosis patients.

Sulphamethoxazole, a substrate of human arylamine N-acetyltransferase, is used in the treatment of cystic fibrosis patients, who metabolise the drug rapidly. Increased metabolic clearance of sulphamethoxazole has been suggested to account for this rapid metabolism. Arylamine N-acetyltransferase type 1 is expressed in erythrocytes and leucocytes and the activity in erythrocytes is shown to contribute approximately 99% of the activity of arylamine N-acetyltransferase type 1 in blood cells.

Arylarnine N-acetyltransferase as a potential biornarker in bladder cancer: fluorescent in situ hybridization and irnmunohistochernistry studies.

Abstract Arylamine N-acetyltransferase isoenzymes NAT1 and NAT2 are encoded at two polymorphic loci on human chromosome 8p22. The two loci have previously been identified using chimeric Yeast Artificial Chromosome (YAC) clones encoding either NAT1 or NAT2 as probes for metaphase chromosomes using fluorescent in situ hybridization. The 8p22 region has been demonstrated to be deleted in highly invasive bladder tumours and since NAT isoenzymes participate in the metabolism of arylamine bladder carcinogens, it is important to determine whether NAT1 and NAT2 gene loci are included in the region of deletion.

Xenogenetics in multifactorial disease susceptibility.

Susceptibility to multifactorial disease includes both genetic and environmental components. These two aspects of susceptibility are interlinked through genetic control of an individual's response to the environment. As a first step in identifying disease susceptibility genes that influence the response of an individual to foreign compounds (xenobiotics), it is necessary to study disorders in which there is an identified environmental trigger.

Slow N-acetylation genotype is a susceptibility factor in occupational and smoking related bladder cancer.

Bladder cancer is a common multifactorial disease and is known to be associated with occupational exposure to arylamines. Smoking is also a recognised contributory environmental cause. Occupational bladder cancer has previously been associated with slow acetylation by N-acetyltransferase (NAT) in humans in phenotyping studies, but more recently there has been some controversy regarding this issue.

Chromosomal localization of human genes for arylamine N-acetyltransferase.

Arylamine N-acetyltransferase is encoded at two loci, AAC-1 and AAC-2, on human chromosome 8. The products of the two loci are able to catalyse N-acetylation of arylamine carcinogens, such as benzidine and other xenobiotics. AAC-2 is polymorphic and individuals carrying the slow-acetylator phenotype are more susceptible to benzidine-induced bladder cancer.

Genotyping human polymorphic arylamine N-acetyltransferase: identification of new slow allotypic variants.

Arylamine N-acetyltransferase catalyses the N-acetylation of primary arylamine and hydrazine drugs and chemicals. N-acetylation is subject to a polymorphism and humans can be categorized as either fast or slow acetylators according to their ability to N-acetylate polymorphic substrates in vivo. Previously, slow acetylation has been linked to four distinct polymorphic N-acetyltransferase (pnat) alleles each of which contains one or more point mutations within the coding region of the pnat gene.