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Biomedical subjects

K Hirvonen

Publications and source records attributed to K Hirvonen.

5 recordsLinked to original sources

Metabolic polymorphism affecting DNA binding and excretion of carcinogens in humans.

A case-control study on lung cancer patients demonstrated the pronounced effect of tobacco smoke on pulmonary carcinogen metabolism and suggested the existence of a metabolic phenotype at higher risk for tobacco-associated lung cancer. Lung cancer patients who were recent smokers showed in their lungs (i) significantly induced CYP1A1-related enzyme activity vs smoking non-lung cancer patients; (ii) increased benzo(a)pyrene (BP) tetrol formation from BP 7,8-diol by lung microsomes; and (iii) high levels of cytochrome P4501a1 by immunohistochemical staining. Levels of bulky aromatic DNA adducts (by 32P-postlabelling) and of BP-diol-epoxide (BPDE) adducts (by HPC/fluorometry) were quantified in lung parenchyma. Aryl hydrocarbon hydroxylase activity and the level of BPDE-DNA adducts (r = 0.91; p < 0.001) and to a lesser degree bulky DNA adducts were correlated. Thus pulmonary CYP1A1 expression (inducibility) controls in part polycyclic aromatic hydrocarbon-DNA adduct formation in tobacco smokers and, therefore, appears to be associated with lung cancer risk. High risk subjects for lung cancer among smokers may be identifiable through genotyping for polymorphic drug metabolizing enzymes in combination with molecular dosimetry of carcinogen-DNA adducts and mutation analysis in target (surrogate) cells. Such studies in a Finnish cohort of lung cancer patients and controls are in progress. Interim results of the effect of metabolic polymorphism on the level of PAH-DNA adducts and on the excretion of mutagens in urine are summarized.

Biotransformation

The effect of small differences in electrode position on EOG signals: application to vigilance studies.

The primary aim of the study was to determine the best electrode positions for EOG signals in vigilance studies. Two-channel recordings were conducted in analogy to the Rechtschaffen and Kales (1968) system. Twenty electrodes (10 electrode pairs) were compared. Both EOG amplitudes and amplitude asymmetries within an electrode pair were studied. The amplitude of the EOG signal is sensitive to relatively small differences in electrode position. This concerns especially distance from the eye, the direction of eye movement and the effect of the upper eye lid movement. Larger and more symmetrical EOG amplitudes were obtained for different eye movements by placing the electrodes more medially than in the conventionally used system. EOG asymmetry in different electrode positions was dependent on the eye movement direction and even on the starting and end points of a movement with equal angular degrees. Most of the data could be explained by a simple monopolar model when combined with the effects of the upper eye lid movements. The most unexpected finding was that the EOG amplitudes of the horizontal and oblique eye movements were significantly larger when the eyes were moving towards an electrode than when they were moving to the opposite direction.

Adult

Validation of computer analysed polygraphic patterns during drowsiness and sleep onset.

A computer system for the automatic analysis of polygraphic records was validated. Records from 9 subjects made during routine MSLT tests were analysed both by two preliminary and one consensus scorer and by a computer system. Special attention was paid to the analysis of drowsiness periods. Therefore a classification system including 7 stages, three for wakefulness and movement, one for drowsiness and three for the sleep stages S1, S2 and SREM was used. Adaptive segmentation was used to divide the records into short segments of variable length (mean 1.6 sec, range 0.5-13.7 sec). The agreements between the computer and visual scores were relatively good for 5 subjects having a prominent occipital alpha activity during wakefulness (range 70-79%) but less promising (range 64-70%) for the other 4 subjects with "poor" occipital alpha activity. The values obtained corresponded to the inter-scorer agreements. Most of the discrepancies were between adjacent stages. At times in the presence of strongly fluctuating EEG amplitudes and especially with the "low-alpha" subjects it was very difficult to determine exactly even by visual scoring when, for instance, drowsiness became sleep. It is concluded that the reliability of the system is sufficient for practical purposes especially if critical parts of the records are visually reexamined. It was found to be difficult to define unambiguous scoring criteria for subjects with poorly defined EEG rhythms giving insufficient landmarks for stage determination.

Adult

A computerized analysis system for vigilance studies.

A digital signal analysis system for vigilance studies is presented. The analysis is based on adaptive segmentation, band pass filtering, nonlinear eye movement detection and rule-based decision making. A preliminary evaluation of seven subjects falling asleep showed that the system is able to detect small vigilance fluctuations reliably.

Artifacts