Search PubMed⌕ Search

Biomedical subjects

H Vainio

Publications and source records attributed to H Vainio.

At least 91 records · Page 5Linked to original sources
PubMed1997

Aspirin for the second hundred years: new uses for an old drug.

The history of aspirin can be traced back to ancient Egypt where extract of willow bark was used to treat inflammation. The active component of the extract was identified as the glucoside of salicylic alcohol. The severe gastric side effects associated with the use of sodium salicylate prompted the synthesis of the o-acetyl-derivative as a possible pro-drug. In fact, acetylsalicylic acid was antiinflammatory, analgesic and antipyretic but also ulcerogenic to the stomach. Acetylsalicylic acid was synthesized one hundred years ago, and was mass-produced under the commercial name of 'Aspirin' (Dreser, 1899) by the German company Bayer for the treatment of fever and rheumatism.

Alzheimer Disease↗
PubMed1997

12th meeting of the Scientific Group on Methodologies for the Safety Evaluation of Chemicals: susceptibility to environmental hazards.

The 12th meeting of the Scientific Group on Methodologies for the Safety Evaluation of Chemicals (SGOMSEC) considered the topic of methodologies for determining human and ecosystem susceptibility to environmental hazards. The report prepared at the meeting describes measurement of susceptibility through the use of biological markers of exposure, biological markers of effect, and biomarkers directly indicative of susceptibility of humans or of ecosystems. The utility and validity of these biological markers for the study of susceptibility are evaluated, as are opportunities for developing newer approaches for the study of humans or of ecosystems. For the first time a SGOMSEC workshop also formally considered the issue of ethics in relation to methodology, an issue of particular concern for studies of susceptibility.

Animals↗
PubMed1997

Interaction between dose and susceptibility to environmental cancer: a short review.

Increased risk of environmentally induced cancer is associated with various types of exposures and host factors, including differences in carcinogen metabolism. Since many carcinogenic compounds require metabolic activation to enable them to react with cellular macromolecules, individual features of carcinogen metabolism may play an essential role in the development of environmental cancer. In this context, cigarette smoking has often been the main type of carcinogenic exposure examined in human studies. Increasing attention has recently been paid to the dose level at which individual susceptibility may be observed. Present studies on increased risk of smoking-related lung cancer associated with phenotypic or genotypic variation of the genes encoding for CYP1A1 or CYP2D6 enzymes are summarized. Similarly, higher risks of lung or bladder cancer seen at various levels of smoking in association with polymorphism of the glutathione S-transferase gene GSTM1 or NAT1 and NAT2 genes involved in N-acetylation are reviewed. Finally, the influence of CYP2E1, GSTM1, or the combined at-risk genotype on the risk of hepatocellular carcinoma in smokers is briefly discussed.

Carcinogens, Environmental↗
PubMed1997

Surveillance and intervention studies on respiratory cancers in asbestos-exposed workers.

A systematic review of the literature on the surveillance of workers at presumed increased risk for respiratory cancer because of their exposure to asbestos revealed surveillance programs at the national, population, industrial, and factory (workplace) levels. Furthermore, 3 randomized chemoprevention trials involving workers exposed to asbestos were found. The nationwide programs to survey problems related to occupational exposure to asbestos were conducted in Europe. Some of the countries have policies for the surveillance of workers exposed either currently or formerly to asbestos. The results of the chemoprevention trials suggest that there are, as yet, no practical tools for efficient, safe chemoprevention of asbestos-induced respiratory malignancies.

Anticarcinogenic Agents↗
PubMed1997

Trends in mesothelioma incidence and occupational mesotheliomas in Finland in 1960-1995.

OBJECTIVES: The study analyzed the recent trend in the incidence of mesothelioma in Finland and evaluated the coverage of reporting work-related mesothelioma. METHODS: The incidence of mesothelioma in 1960-1995 was retrieved from the Finnish Cancer Registry, and the number of asbestos-associated work-related mesotheliomas were taken from the Finnish Register of Occupational Diseases. RESULTS: The annual number of mesotheliomas increased rapidly in 1975-1990. In the 1990s, the age-adjusted incidence remained relatively stable for Finnish men. The annual number of cases still increased among men over 65 years of age, but decreased slightly among men under 55 years of age and among women. About 35 annual cases were diagnosed among men and 10-15 among women in the mid-1990s. The reporting of work-related mesotheliomas improved during the Finnish asbestos program in 1987-1992. In 1993-1995 about 30 annual cases (ie, about 90% of all pleural and 50% of the peritoneal mesotheliomas in men) were reported to be work-related. CONCLUSIONS: The increasing trend in the incidence of mesothelioma in Finland has slowed down in the 1990s, and the maximum of asbestos-related cases in the early 2000s will probably be clearly less than the 100 annual cases estimated in the early 1990s. If the observed trend continues up to 2010, about 40-50 cases among men and 10-20 among women will then be diagnosed annually. Altogether 40-50 of these cases would be related to occupational asbestos exposure.

Aged↗
PubMed1997

An international evaluation of the cancer-preventive potential of nonsteroidal anti-inflammatory drugs.

The IARC convened a Working Group of experts in Lyon, France, on April 2-8, 1997 to evaluate the cancer-preventive activity of four nonsteroidal anti-inflammatory drugs (aspirin, sulindac, piroxicam, and indomethacin). Epidemiological observational studies of aspirin that differed in design, location, population, and motivating hypothesis have consistently shown that regular use lowers the risk for colorectal cancer by up to 50%; however, the one randomized trial did not show protection by aspirin. Definite evidence of chemopreventive activity normally requires data from appropriately designed randomized trials. The strength of the scientific evidence that aspirin prevents colorectal cancer in humans was thus considered to be limited. In animal models, there was sufficient evidence that aspirin prevented against cancer. Aspirin and aspirin-like drugs may have an important adverse side effects, the most frequent of which are gastrointestinal disturbances ranging in severity from dyspepsia to peptic ulcer. Given the remaining uncertainties in the preventive effect and the risk of adverse side effects, detailed consideration of the total benefits and of toxicity will be required before widespread use of aspirin for the prevention of colorectal cancer can be recommended. Sulindac shows promise in reducing the number and size of adenomatous polyps in patients with familial adenomatous polyposis. Further research is required, however, to determine whether and to what extent the risk for colorectal cancer in such patients is reduced. In people without familial adenomatous polyposis, there is inadequate evidence that sulindac has cancer-preventive activity. Fewer data were available on piroxicam and indomethacin than on aspirin and sulindac. Although these drugs consistently prevent colorectal cancers in experimental animal models, the evidence that they prevent colorectal cancer in humans was considered to be inadequate. The results of the meeting, including recommendations for future research, will be published as Volume 1 of the IARC Handbooks of Cancer Prevention.

Animals↗
PubMed1996

Glutathione S-transferase and N-acetyltransferase genotypes and asbestos-associated pulmonary disorders.

BACKGROUND: Humans vary in their ability to metabolize endogenous and exogenous compounds. Glutathione S-transferases (GSTs) and N-acetyltransferases (NATs) are enzymes involved in the detoxification of hazardous agents. The GSTM1 and GSTT1 genes exhibit null (i.e., deletion) polymorphisms; in specific individuals, homozygous deletion (i.e., both copies lost) of these genes can be detected. Polymorphism of the NAT2 gene results in slow and fast acetylators of potentially toxic substances. The GSTM1-null and the NAT2 slow-acetylator genotypes have been associated with increased risks for the development of environmentally induced cancers. PURPOSE: We assessed whether homozygous GSTM1-null or GSTT1-null genotypes or the NAT2 slow-acetylator genotype were associated with increased risks for the development of malignant and nonmalignant asbestos-related pulmonary disorders in a cohort of Finnish construction workers. METHODS: The study population consisted of 145 asbestos insulators who were classified as having been exposed to high levels of asbestos; 69 of these individuals had no pulmonary disorders (control subjects), and 76 had either malignant mesothelioma (n = 24) or nonmalignant pulmonary disorders, such as asbestosis and/or pleural plaques (n = 52). Lymphocyte DNA and the polymerase chain reaction were used to determine the GSTM1, GSTT1, and NAT2 genotypes of the study subjects. Odds ratios (ORs) and 95% confidence intervals (CIs) estimating the relative risks of disease associated with specific genotypes were calculated from 2 x 2 tables by use of Fisher's exact method. RESULTS: Risks for the development of asbestos-related pulmonary disorders were not affected significantly by homozygous deletion of the GSTM1 or GSTT1 genes. However, the risk of developing both malignant and nonmalignant pulmonary disorders for individuals with a NAT2 slow-acetylator genotype was more than twice that observed for those with a NAT2 fast-acetylator genotype (OR = 2.3; 95% CI = 1.1-4.7); the risk of developing malignant mesothelioma for NAT2 slow acetylators was increased almost fourfold (OR = 3.8; 95% CI = 1.2-14.3). Individuals who lacked the GSTM1 gene and possessed a NAT2 slow-acetylator genotype had a risk of developing malignant and nonmalignant pulmonary disorders that was approximately fivefold greater than that observed for those who had the GSTM1 gene and a NAT2 fast-acetylator genotype (OR = 5.1; 95% CI = 1.6-17.6); these individuals had a fourfold increased risk of developing nonmalignant pulmonary disorders (OR = 4.1; 95% CI = 1.1-17.2) and an eightfold increased risk of developing malignant mesothelioma (OR = 7.8; 95% CI = 1.4-78.7) when compared with the same reference group. CONCLUSIONS: Individuals with homozygous deletion of the GSTM1 gene and a NAT2 slow-acetylator genotype who are exposed to high levels of asbestos appear to have enhanced susceptibility to asbestos-related pulmonary disorders.

Acetylation↗
PubMed1996

Expression of cytochrome P450s and glutathione S-transferases in human esophagus with squamous-cell carcinomas.

In order to clarify the expression of cytochrome P450 and glutathione S-transferase in human esophagus, 41 samples of human esophagus with squamous-cell carcinoma were investigated by immunoblot analysis and enzyme assays. Cytochrome P450 1A2/1 was clearly expressed in microsomes, and the amount in samples with tumorous tissue was significantly greater than that in samples without tumourous tissues or in liver; cytochrome P450 2B6 and 3A4/3 were expressed polymorphically. Aryl hydrocarbon hydroxylase activity was detected in microsomes and was greater in samples from smokers than non-smokers. Patients who both smoked and drank alcohol, however, had activity similar to that of patients without these habits. Glutathione S-transferase M1 and A1/2 protein existed polymorphically in cytosol, and glutathione S-transferase P1-1 was detected in all samples. The frequency of expression of the glutathione S-transferase A1/2 protein was greater in patients with M1 protein than in those without; no difference in the expression was seen for glutathione S-transferase P1-1. Neither smoking nor drinking influenced the expression or activity of glutathione S-transferase. Our data support the idea that some carcinogens can be directly activated or inactivated in human esophageal epithelium.

Alcohol Drinking↗
PubMed1996

Pulmonary asbestos bodies and asbestos fibers as indicators of exposure.

OBJECTIVES: The aim of the study was to analyze the correlation between pulmonary concentrations of asbestos bodies and asbestos fibers and to characterize asbestos body counts from lung tissue of Finnish patients occupationally exposed and unexposed to asbestos. METHODS: Ninety-nine surgically treated lung cancer patients were investigated. The number of asbestos bodies in iron-stained 5-micrometers histological lung tissue sections was determined by optical microscopy, and the pulmonary concentration of asbestos fibers was assessed by scanning electron microscopy. The correlation between asbestos body and asbestos fiber counts was calculated with linear regression. The asbestos body and asbestos fiber concentrations were also compared with exposure history according to a personal interview of the patients. RESULTS: The average number of asbestos bodies ranged from < 0.1 to 750 asbestos bodies per tissue section. All the cases with definite exposure showed an average of at least one asbestos body per tissue section. An average of at least one asbestos body per section was, however, detected in 34% of the patients with unlikely exposure. The regression equation log (AF) = -0.429 + 0.600.log (AB) was found to predict the concentration of asbestos fibers (AF, 10(6) fibers.g-1) corresponding to a given number of asbestos bodies (AB) in a section of lung tissue. CONCLUSIONS: The background level of asbestos bodies in the lungs of patients with no specific asbestos exposure seems to be higher in Finland than in other countries. In medicolegal cases, the methodological variation involved in asbestos fiber and asbestos body counting must be recognized and all available exposure data should be used to produce the best possible estimate of the exposure.

Adult↗
PubMed1996

A molecular and epidemiological study on bladder cancer: p53 mutations, tobacco smoking, and occupational exposure to asbestos.

In this study, we found an unexpected association (crude odds ratio = 2.8; 95% confidence interval = 0.9-8.4) between definite work-related exposure to asbestos and carcinoma of the urinary bladder in a small group of patients (n = 28) initially recruited as referents for an epidemiological feasibility study on the occupational causes of lung cancer. We extended the study by using molecular methods to examine mutations in the p53 tumor suppressor gene in the same cases of bladder cancers. The same number of archival samples of transitional cell carcinoma, mainly of grade 3, were added to the analysis. We failed to show any association between occupational exposure to asbestos and p53 mutations among bladder cancer patients. We observed an increasing occurrence of p53 mutations in nonsmokers (5 of 17, 29%), former smokers (8 of 21, 38%), and current smokers (9 of 16, 56%) in that order; however, this was not statistically significant. The most prevalent type of mutation was G:C to A:T transition. Tumor grade was not associated with the frequency of mutations, but the higher stage (T3-T4) tumors appeared to have mutations more frequently than did the less invasive tumors (T1-T2).

Adult↗
PubMed1995

Pulmonary expression of glutathione S-transferase M3 in lung cancer patients: association with GSTM1 polymorphism, smoking, and asbestos exposure.

To characterize the relative roles of glutathione S-transferases (GST) M1 and M3 in the susceptibility to lung cancer, the pulmonary expression of GSTM3 was quantified immunochemically and related to the GSTM1 genotype in 100 lung cancer patients. Among active smokers and recent ex-smokers (for 6 years or less), parenchymal GSTM3 expression was lower in patients with a homozygous GSTM1 null genotype than in those who were GSTM1 positive and had similar smoking habits (P < 0.001 and P = 0.004, respectively). However, in long-term ex-smokers (for 15 years or longer) GSTM3 was not affected by the GSTM1 genotype. Among active smokers and recent ex-smokers who were homozygous GSTM1 null, those with a definite or probable exposure to asbestos expressed GSTM3 at significantly higher levels than those for whom it was unlikely (P = 0.04). A similar effect of the homozygous GSTM1 null genotype on GSTM3 expression was not detected in the bronchial epithelium when GSTM3 was visualized immunohistochemically. Different mechanisms may result in an increased risk of either squamous cell or adenocarcinomas in patients with the homozygous GSTM1 null genotype. Low expression of GSTM3 due to smoking in the parenchymal lung of GSTM1 null individuals can theoretically favor the development of adenocarcinoma. Our data indicated a predominance of this tumor type in patients with low expression of GSTM3.

Adult↗
PubMed1995

p53 antibodies in the sera of lung cancer patients: comparison with p53 mutation in the tumour tissue.

This study examined the sensitivity and specificity of serum auto-antibodies to p53 protein as a non-invasive marker of p53 genetic alterations or protein accumulation in lung cancer cases. A sensitive ELISA to detect serum p53 antibodies was developed and used to examine sera from 186 patients undergoing pulmonary surgery for a suspected lung cancer. Target antigens in ELISA were wild-type p53 protein and 5 peptides covering the N- and C-terminal parts of the protein. Sixteen sera were positive for serum p53 antibodies in both ELISAs and all were among the 136 patients with confirmed primary lung carcinoma. Of 50 patients with other pulmonary diseases, none had p53 antibodies. In 92 cancer patients exons 5 to 8 of the p53 gene were examined for mutations by denaturing gradient gel electrophoresis and direct sequencing of PCR products. Forty-seven tumours had a p53 mutation and 7 (15.2%) of these were positive for p53 antibodies. Two patients had serum antibodies but no detectable mutation in exons 5 to 8. Frequencies of p53 mutations and serum antibodies were higher in squamous cell carcinoma patients than in adenocarcinoma. Accumulation of p53 protein in tumour tissue was observed in 32 patients, but only 5 were positive for p53 antibodies. In conclusion, serum p53 antibodies were detected only in a proportion of lung cancer cases, but the majority were specifically associated with a detectable p53 mutation in the tumour.

Autoantibodies↗