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Biomedical subjects

S Anttila

Publications and source records attributed to S Anttila.

At least 73 records · Page 4Linked to original sources
PubMed1993

Polymorphism in CYP1A1 and CYP2D6 genes: possible association with susceptibility to lung cancer.

Polymorphism of CYP2D6 gene encoding for debrisoquine hydroxylase was determined genotypically for 94 controls and 77 lung cancer patients using a polymerase chain reaction-based application. Both of the point mutations that give rise to deficient alleles of the CYP2D6 gene are detectable by this method. Out of the 94 healthy controls, 3 individuals (3.2%) had poor metabolizer (PM) genotypes, whereas no PM genotypes were detected in the lung cancer patient group. We observed no difference in the allelic frequencies for either homozygous extensive metabolizers (EMs) or heterozygous EMs between the lung cancer patients and the healthy controls. However, the absence of the poor metabolizer genotype (0/77) in the lung cancer patients is compatible with the hypothesis that there is an increased risk of lung cancer for individuals who are extensive metabolizers of debrisoquine. Another member of the cytochrome P450 gene superfamily that has attracted interest for its potential role in human pulmonary carcinogenesis is the CYP1A1 gene. In CYP1A1 gene studies, a polymorphic site assessable to MspI gives rise to two different hybridizable fragments in a Southern blot analysis (alleles C1 and C2, respectively). The C2C2 genotype has previously been associated with an increased risk of lung cancer. So far 74 lung cancer patients, 30 patients with lung diseases other than cancer, and 118 healthy controls have been studied for CYP1A1 gene polymorphism. No association between the MspI restriction fragment length polymorphism in the CYP1A1 gene and lung cancer susceptibility has been found.

Alleles↗
PubMed1993

Interaction between smoking and asbestos in human lung adenocarcinoma: role of K-ras mutations.

To investigate the role of tobacco smoking and asbestos fibers in the etiology of human lung cancer, we examined the activating point mutations in the K-ras oncogene in DNA samples from 49 patients. Mutations were found more often in tissue from adenocarcinomas (12/21) than in tissue from tumors other than nonadenocarcinomas of the lung (3/28). Among the adenocarcinoma patients, asbestos exposure was predictive of K-ras mutation (odds ratio, 4.9; 95% confidence interval, 0.7-34.3); in patients with other types of lung cancer, the relation appeared to be an inverse one, but the numbers were small. The proportion of heavy smokers (over 50 pack-years) was 60% among people with K-ras mutations and 35% among the K-ras-negative subjects, suggesting that smoking causes K-ras mutations. If mutations in K-ras genes are caused by smoking, asbestos would act as a promoting agent by conferring selective growth conditions for clonal expansion on these mutated cells. Asbestos may favor recruitment of (initiated) K-ras mutation-positive cells in the multistage process of carcinogenesis by stimulating cellular growth.

Adenocarcinoma↗
PubMed1993

Lobe of origin of lung cancer among asbestos-exposed patients with or without diffuse interstitial fibrosis.

The effect of asbestos exposure and asbestos-associated fibrosis on the lobe of origin of lung cancer was studied among 108 lung cancer patients. The asbestos-exposed patients had significantly more lower lobe tumors than the unexposed patients. Similar results were obtained when occupational history or lung fiber concentration was used as an indicator of past occupational exposure to asbestos. The predominance of lower lobe tumors occurred even among exposed patients with no histological signs of asbestosis in their lung specimens. Both bronchial and peripheral cancers showed a lower lobe predominance among the exposed patients. Smoking history did not affect the lobar distribution of the tumors. No significant differences occurred for the histological cell types of the tumors between the exposed and unexposed patients. Patients with asbestosis had, however, more adenocarcinomas than the unexposed patients. The results indicate that asbestos may increase the risk of lung cancer even in the absence of asbestosis.

Adult↗
PubMed1992

Stereoselective metabolism of (-)-benzo[a]pyrene-7,8-diol by human lung microsomes and peripheral blood lymphocytes: effect of smoking.

Benzo[a]pyrene (B[a]P)-tetrols formed after stereoselective cytochrome P450-dependent metabolism from (-)-trans-7,8-dihydroxy-7,8- dihydrobenzo[a]pyrene [(-)-B[a]P-7, 8-diol] by lung microsomes (n = 19) and peripheral blood lymphocytes (n = 13) from lung cancer patients were measured, and the effect of smoking explored. B[a]P-tetrols were quantified by an HPLC/fluorescence assay with a detection limit of approximately 300 attomol, after incubation with peripheral blood lymphocytes or microsomes from lung cancer patients who were current cigarette smokers, ex-smokers and non-smokers. In lymphocytes from these subjects, high, medium and low metabolic activities respectively for (-)-B[a]P-7,8-diol to tetrol conversion were found, but there was no statistically significant difference between smokers, ex-smokers and non-smokers. When the B[a]P-tetrol formation by human lung microsomes was measured, recent smokers had 4- to 7-fold higher (P = 0.04) metabolic activity than ex-smokers and non-smokers. The mean lung microsomal arylhydrocarbon hydroxylase (AHH) activity was three times higher in smokers than in non-smokers and was undetectable in ex-smokers. AHH activity was correlated with tetrol formation in the same lung microsomal samples (r = 0.62, P less than 0.01 in smokers; and r = 0.67, P less than 0.01 in all subjects). When subjects were grouped according to smoking habits, however, no correlation was detected between mean tetrol formation by lung microsomes and that of lymphocytes. Thus, lymphocytes cannot serve as a surrogate for lung microsomes concerning the pulmonary metabolism of (-)-B[a]P-7,8-diol. The much higher B[a]P-tetrol formation observed in lung microsomes from smokers is in accord with a reported higher pulmonary AHH activity, cytochrome P450IA level, and CYP1A1 gene expression in recent tobacco smokers.

Adolescent↗
PubMed1992

Metabolic cytochrome P450 genotypes and assessment of individual susceptibility to lung cancer.

Three polymorphic cytochrome P450 genes that have attracted interest for their potential role in human pulmonary carcinogenesis, i.e. CYP1A1, CYP2D6 and CYP2E1, were studied in a population consisting of 106 lung cancer patients and 122 healthy controls. Polymorphism of the CYP2D6 gene encoding for debrisoquine hydroxylase was determined using XbaI restriction fragment length polymorphism (RFLP) analysis together with a PCR based method. All of the three most common presently known defective alleles of CYP2D6 were detected by this application. Subjects having genotypes either homozygous or heterozygous for the CYP2D6 wild type alleles were classified as extensive metabolizers (EMs) of debrisoquine whereas poor metabolizers (PMs) had two defective alleles. The PM individuals are thought to be less prone to develop lung cancer. The CYP1A1 and CYP2E1 genes were studied by RFLP analyses using Msp I and Dra I restriction enzymes, respectively, giving rise to two different sized hybridizable fragments in Southern blot analyses. In these RFPL analyses genotypes homozygous to the mutated allele have been presented as potent determinants of individual lung cancer risk. In the present study no association between polymorphic CYP1A1 and CYP2E1 genotypes and susceptibility to lung cancer was found. However, CYP2D6 polymorphism studies of the 122 healthy controls revealed seven poor metabolizer genotypes (5.7%), which compares well with the previously observed phenotypic distribution in the Finnish population, whereas only one PM genotype (1/106) was found among the lung cancer patients. These results agree with the previous suggestions that PMs of debrisoquine are less susceptible to lung cancer than EMs.

Cytochrome P-450 CYP1A1↗
PubMed1992

Fibres and asbestos bodies in bronchoalveolar lavage fluids of asbestos sprayers.

The alveolar content of fibres and asbestos bodies was assessed by bronchoalveolar lavage (BAL) in 21 asbestos sprayers. Transmission and scanning electron microscopy (TEM and SEM) and two light microscopical (LM) methods, cytocentrifugation, and Millipore filtration were used. The subjects had been exposed mainly to crocidolite asbestos for an average of 2.8 (range 0.2-13) years in 1950-75. The mean (median) total fibre count (of asbestos bodies and uncoated fibres) per ml of BAL fluid was 5500 (2800) by TEM and 2900 (1000) by SEM. The mean (median) count of asbestos bodies per ml with LM was 810 (500) with cytocentrifugation and 750 (480) with Millipore filtration, 840 (320) by TEM, and 1750 (420) by SEM. The mean proportion of coated fibres was 35% by TEM and 45% by SEM. The mean length of the coated fibres was 22 (range 4-65) microns by TEM and 34 (range 4.5-170) microns by SEM. The total fibre count exceeded 1000 fibres per ml in 70% of the cases by TEM. Asbestos body counts exceeded 1 per ml in 95% of the cases by LM. The fibre counts by SEM were in good accordance with counts by TEM except in a few cases in which the TEM result was considerably higher. In these cases the proportion of coated fibres was also low. All four counting methods appeared to give consistent results in heavily exposed cases when fibre load in the lungs was high. The counting of asbestos bodies may, however, underestimate the total alveolar fibre load in some cases.

Adult↗
PubMed1992

Immunohistochemical detection of pulmonary cytochrome P450IA and metabolic activities associated with P450IA1 and P450IA2 isozymes in lung cancer patients.

The main polycyclic aromatic hydrocarbon-inducible cytochrome P450 was studied in lung tissue from 57 lung cancer patients by immunohistochemistry, using a monoclonal antibody (1-7-1) that recognizes P450IA1 and P450IA2 isozymes. The intensity of immunostaining was compared with the pulmonary activity of a P450IA1-dependent enzyme, aryl hydrocarbon hydroxylase (AHH), and with P450IA2-related metabolic activity estimated from the ratio of caffeine metabolites in urine. Immunostaining was not observed in peripheral lung tissue of nonsmokers or ex-smokers but was seen in the bronchiolar and alveolar epithelium of all patients who were smokers and had a peripheral carcinoma (16/16) and of 60% (10/17) of those who had a bronchial carcinoma. AHH activity was positively related to the intensity of immunostaining, and an almost 2-fold increase due to smoking was detected in the ratios of caffeine metabolites. These results demonstrate that tobacco smoke induces P450IA1 in the lung and probably P450IA2 in the liver, and suggest a role for certain metabolic phenotypes of P450IA1 in peripheral pulmonary carcinoma.

Adenocarcinoma↗
PubMed1992

Detection of ras gene mutations in human lung cancer: comparison of two screening assays based on the polymerase chain reaction.

We studied the prevalence of point mutations in ras oncogenes (K-ras and N-ras) in DNA from white blood cells and tumor tissue from 36 untreated patients with non-small-cell lung cancer, all of whom were smokers or ex-smokers. We observed somatic K-ras mutations in one-third of the lung carcinomas studied but no N-ras mutation. K-ras codon 12 mutations were found more frequently in adenocarcinomas than in the other histopathological subtypes studied. More than 60% (10/16) of the lung adenocarcinomas had a codon 12 mutation, most of which were G to T transversions. No mutations was found in white blood cell DNA. Two polymerase chain reaction screening methods, oligonucleotide hybridization and denaturing gradient gel electrophoresis (DGGE), were used to detect the mutations. The oligonucleotide method appears to be more sensitive than DGGE, but DGGE proved to be a reliable nonradioactive method for rapid screening of point mutations in genes relevant to carcinogenesis.

Adenocarcinoma↗
PubMed1991

Smoking and peripheral type of cancer are related to high levels of pulmonary cytochrome P450IA in lung cancer patients.

A specific member of the cytochrome P450 superfamily of enzymes, designated P450IA (including 2 isozymes, P450IA1 and P450IA2), which is involved in the metabolic activation of polycyclic aromatic hydrocarbons and aromatic amines, was studied in lung tissue from 25 lung cancer patients by immunohistochemistry. The pulmonary activity of a P450IA1-dependent enzyme, aryl hydrocarbon hydroxylase (AHH), from the same patients was also measured. Cytochrome P450IA was localized principally in the peripheral airways in alveolar epithelium of types I and II and in ciliated columnar and cuboidal bronchiolar epithelium. The amount of P450IA in the bronchial wall was minimal and was localized mainly in the capillary endothelium and the epithelium of the bronchial glands. Smoking was the most important factor related to the presence of P450IA and the AHH activity in lung tissue. None of the 10 ex-smokers, but all except I of the current smokers had detectable level of P450IA. The localization of the cancer was also correlated with the presence of cytochrome P450IA. Peripheral lung tissue stained positively in all patients with a peripheral adenocarcinoma who currently smoked (8/8) but in less than half of those with a bronchial cancer who were smokers (3/7). Our data suggest that the smokers who have an inducible cytochrome P450IA are especially at increased risk of developing lung cancer of the peripheral adenocarcinomatous type.

Adenocarcinoma↗
PubMed1991

Dupuytren's contracture: the long-term results after day surgery.

220 operations in 211 hands in 160 consecutive patients suffering from Dupuytren's contracture were performed from 1976 through 1984 at the Kuopio University Central Hospital in Finland. 179 operations were carried out as day cases. The mean follow-up was 3.2 years. Sub-total fasciectomy resulted in good immediate and long-term improvement in 86% of patients. The recurrence rate was 27%. Surgical treatment of Dupuytren's contracture was well-suited to day surgery. A properly planned follow-up programme is suggested because of the relatively high rate of recurrence, which usually appeared within two years after operation.

Adult↗
PubMed1991

Diploid predominance and prognostic significance of S-phase cells in malignant mesothelioma.

70 histologically verified, malignant mesotheliomas were analysed by flow cytometry for DNA content and S-phase fraction (SPF) of tumour cells. 60% (42/70) were DNA diploid. 18 of the 28 aneuploid tumours were near-diploid with DNA indices of 1.3 or less. SPF could be calculated in 51 cases. SPF was significantly higher in aneuploid (median 16.0%) than in diploid tumours (median 5.6%). DNA ploidy was not a prognostic determinant; survival was the same for both aneuploid and diploid tumours. SPF, however, was significantly correlated (P = 0.039) with prognosis. Patients who had tumours with a low SPF survived almost twice as long as those with a high SPF. Thus malignant mesothelioma has a peculiar DNA ploidy pattern compared with many other solid tumours, with a predominance of diploid or near-diploid type cells. As in many other tumours, SPF may be used as a clinically relevant prognostic indicator.

Adult↗
PubMed1991

Functional capacity in two elderly populations aged 75 or over: comparisons at 10 years' interval.

The functional capacity of two different non-institutionalized elderly populations and the resources available were compared in the same geographical area at 10 years' interval. The study shows that a 1.5-fold increase in the non-institutionalized population aged 75 or over combined with a fixed number of institutional beds in 10 years resulted in more disability among the elderly at home. The nursing home population at the latter point of time was older and showed a higher mortality, indicating increased pressure and selection to the nursing home. The first study comprised 82.8% and the second 89.2% of all community-living persons aged 75 or over. In 1988, the functional status of the aged living at home was significantly lower than in 1978, in 8 out of 12 functional activities of daily living (ADL). The Basic ADL Index decreased significantly both in men and in women, and mobility also deteriorated. The Instrumental ADL Index decreased significantly in men, while the Index was equally poor in women in both interviews. The poor functional status of the elderly in 1988 was accompanied by moving to the town centre and considerably improved housing standards. Home care services had more than doubled, and home nursing visits had also increased.

Activities of Daily Living↗
PubMed1989

High concentrations of chromium in lung tissue from lung cancer patients.

The pulmonary chromium content was determined by plasma atomic emission spectrometer (DCP-AES) from 53 lung cancer and 43 control patients, and compared with smoking habits, severity of emphysema and occupational history. The chromium content from the lung cancer patients was higher than that from the smoking (P less than 0.025) or nonsmoking control patients (6.4 +/- 4.3, 4.0 +/- 4.0, and 2.2 +/- 0.6 microgram/g dry weight, respectively). A positive correlation between the pulmonary chromium and smoking time (P less than 0.025) and the severity of emphysema (P less than 0.001) was found in the control but not in the cancer patients. The difference in the pulmonary chromium content was greatest between those lung cancer and control patients who were light smokers or had mild emphysema. This group of lung cancer patients included subjects with occupational exposure to chromium. The possibility of occupational cancer should be considered especially with light smokers. The grade of emphysema and metals such as chromium accumulating from tobacco could serve as objective indicators of smoking.

Aged↗
PubMed1989

The general health questionnaire (GHQ) as a predictor of hospital care and mortality in the non-institutionalized elderly.

The general health questionnaire (GHQ) and its relation to hospital care and risk of death were studied prospectively in the total elderly population living in a community in northern Finland. Of the eligible elderly, 982 or 85% took part in the study, returning the GHQ. A high score on the questionnaire was considered an indicator of minor psychiatric illness. It was found that the average number of hospital days, calculated per person-years, was twice as high in the high scorers than in the low scorers. When the effects of age and certain diseases were controlled for, the high scoring men and women had a significantly higher risk of being hospitalized for at least ten days over a five-year period than the 0-1 scorers. The risk ratio was 1.6 and 1.4 for men and women, respectively. The ten-year mortality was significantly higher in the high scoring men and women than in the low scorers, when the effects of age and certain diseases were controlled for. The risk ratios for both men and women were 1.4. The GHQ was found to predict hospital care, physician visits, home services and mortality in a representative group of rural elderly people.

Aged↗
PubMed1989

Cadmium and chromium as markers of smoking in human lung tissue.

The pulmonary cadmium (Cd) and chromium (Cr) contents from 45 decreased persons from Northern Finland were determined by plasma emission spectrometry (DCP-AES). These subjects did not have any malignant diseases or known occupational exposure to heavy metals. The pulmonary metal concentrations were compared with smoking history, pulmonary emphysema, age, and occupation. The mean Cd concentrations for the nonsmokers, smokers, and exsmokers were 0.4 (SD +/- 0.4), 3.0 (SD +/- 2.2), and 1.1 (SD +/- 1.0) micrograms/dry wt, and the corresponding values for Cr were 1.3 (SD +/- 0.9), 4.3 (SD +/- 3.3), and 4.8 (SD +/- 4.0) micrograms/g dry wt, respectively. The pulmonary Cr content increased with age and smoking time, but showed no connection with occupation. The Cd content was dependent only on smoking-related variables, increasing with the amount of tobacco smoked. The pulmonary Cd was seen to return to the level of nonsmokers in 21-22 years after cessation of smoking, whereas Cr showed no decreasing tendency with the time since smoking stopped.

Aged↗
PubMed1989

Smoking and the pulmonary mineral particle burden.

The total pulmonary mineral particle burden and types of environmental particles were assessed in relation to smoking in 11 unselected autopsy lungs from adult male smokers and paired male non-smokers matched by age and lung. The lungs were fixed intrabronchially with formalin-polyethylene glycol-alcohol solution at a standard pressure and air-dried. A sample of 1-2 cm3 was taken from the posterior or apicoposterior segment of the right/left upper lobe and plasma ashed at low temperature. The mineral particles were identified by scanning transmission electron microscopy (STEM), electron microprobe analysis and electron diffraction. The number, mass and volume were calculated from the STEM image. The smokers' lung tissue had a lower number (54 +/- 15 X 10(6), mass (5.1 +/- 3.2 micrograms), volume (183 +/- 122 X 10(-5) mm3) and surface area (104 +/- 44 mm2/cm3 of lung tissue) of particles than the non-smokers' lung tissue (68 +/- 42 X 10(6), 12.6 +/- 13.4 micrograms, 468 +/- 501 X 10(-5) mm3 and 191 +/- 167 mm2/cm3 of lung tissue, respectively). All mineral types except talc were more numerous in the non-smokers' than in the smokers' lung tissue. The mineral particles were typical of the Finnish bedrock: quartz 15 +/- 7%, plagioclase 8 +/- 4%, microcline 13 +/- 5%, micas 22 +/- 10%, talc 4 +/- 4% and kaolinite 10 +/- 5%. Fibres were observed in only 2 cases, amounting to 1% in each. The lower mineral particle content of the smokers' lungs probably reflects more active clearance mechanisms caused by cigarette smoke.

Adult↗