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Biomedical subjects

M Klockars

Publications and source records attributed to M Klockars.

At least 55 records · Page 3Linked to original sources

Effect of retirement on health and work ability among municipal employees.

A questionnaire was sent to 6257 active employees, mean age 50.5 years, in 1981, and again in 1985, when 4255 of the workers were still actively working, 402 had retired because of age, and 468 had retired for medical reasons. After retirement, regardless of reason or previous work content, the prevalence of musculoskeletal diseases changed little among the women but increased markedly among the men retired from mental work. Among the men retired from mental work because of age, the prevalence of cardiovascular diseases increased after retirement. After disability pensioning the prevalence of cardiovascular diseases increased for both the men and the women. The prevalence of poor work ability increased in all the work categories irrespective of the type of retirement. Work ability did not improve after old-age pensioning, but health status was improved among the men and women in some occupational groups. Therefore light, part-time work should not be excluded for retired people.

Cardiovascular Diseases↗

Work-related stress symptoms of aging employees in municipal occupations.

The objective of the study was to investigate the relationship between stress symptoms and work stressors among aging employees in municipal occupations. The subjects were 1799 men and 2456 women aged 48-62 years and representing 40 different occupations. Stress reactions were identified on the basis of long-term cardiorespiratory, musculoskeletal, and psychological symptoms. Work stressors were described by means of physical and mental work demands. Two factors describing the possibilities for regulating one's own work load were used as indicators for the adjustment of work according to individual capacities. The effect of work stressors on cardiovascular, musculoskeletal, and psychological symptoms was studied in separate analyses, controlling for the relevant disease group. Both chronic diseases and work stressors were related to the occurrence of symptoms. However, stress identified on the basis of symptoms was not only a phenomenon determined by health status. Work stressors and possibilities for regulating one's own work load were systematically related to symptom level.

Age Factors↗

Work load and individual factors affecting work disability among aging municipal employees.

A cohort of 6165 municipal workers 44 to 58 years of age was followed during 1981-1985. The most impairing work loads were poor work postures and poor physical climate, whereas good possibilities for development at work prevented work disability. Aging particularly increased the incidence of work disability, whereas physical exercise maintained work ability. Among workers who suffered from any cardiovascular disease, a low level of muscular work and a high level of leisure-time physical exercise decreased work disability. Compared with the work ability of active workers, work disability was more linked to individual than to work load factors.

Age Factors↗

Viral antibodies in multiple sclerosis. A nationwide co-twin study.

Serum viral antibody titers against 21 viruses were studied in 19 of 23 same-sex twin pairs with multiple sclerosis derived from the Finnish Twin Cohort. Thorough neurologic examinations showed two monozygotic pairs to be concordant, whereas all dizygotic pairs were discordant. Special attention was given to measles, mumps, and rubella viruses, against which the antibody levels were determined with the complement fixation, hemagglutination inhibition, hemolysis-ingel, and enzyme immunoassay methods. Epstein-Barr virus antibody levels were determined by enzyme assay. In pairwise comparisons, the measles, mumps, and Epstein-Barr virus-IgG antibody levels were more often elevated in the patients with multiple sclerosis, compared with the healthy co-twins. The same antibody levels were more often above the median in the diseased twin, compared with the healthy twin, but the difference was not significant. No human T-cell lymphotropic virus type I antibodies were found in any of the individuals examined. The total IgG, IgA, and IgM levels did not differ between the diseased and healthy subjects. The HLA types, severity of the disease, and cell-mediated immunity parameters did not influence antibody levels.

Antibodies, Viral↗

Effect of immunoglobulins on mineral dust-induced production of reactive oxygen metabolites by human macrophages.

Mineral dust-induced production of reactive oxygen metabolites (ROMs) by human monocyte-derived macrophages was investigated using lucigenin-dependent chemiluminescence. Chrysotile asbestos alone caused only weak ROM production by macrophages, but the addition of polyclonal immunoglobulin enhanced the reaction strongly. The phenomenon was seen with 1-, 4-, and 7-day-old cell cultures. Polyclonal immunoglobulin also slightly enhanced the ROM responses induced by amosite, crocidolite, and quartz dust. The enhancing effect could be achieved with several monoclonal immunoglobulins (isolated from the sera of myeloma patients), but IgA and IgG had the strongest effects. We suggest that immunoglobulins may interact with mineral dusts in a "nonimmunological," antigen-independent way and that the so-formed dust-immunoglobulin complexes may amplify the production of ROMs by inflammatory cells. This may explain a number of in vivo phenomena in which immune responses (for instance hypergammaglobulinemia and the presence of autoantibodies) have been shown to relate to the progression of mineral dust-induced pulmonary disease.

Antibodies, Monoclonal↗

Asbestos fibers induce release of collagenase by human polymorphonuclear leukocytes.

The asbestos fibers chrysotile and crocidolite cause a dose-dependent release of specific granule collagenase by human polymorphonuclear leukocytes (PMNL). Release of azurophil granule elastase was induced by the asbestos fibers at higher concentrations, suggesting that asbestos fibers primarily cause the release of specific granule contents of human PMNL. Wollastonite, a fibrous silicate mineral, causes a weaker collagenase release and no elastase release. The collagenase was released in inactive, latent form. Carboxymethyl cellulose (CMC), an agent known to blunt chrysotile-induced hemolysis and production of reactive oxygen metabolites by human PMNL, specifically inhibits chrysotile-induced release of collagenase. Chrysotile asbestos was found to bind the PMNL serine proteinase cathepsin G. A role of collagenase release, production of reactive oxygen metabolites and cathepsin G binding by chrysotile for the perpetuation of the asbestos-induced alveolitis is suggested.

Asbestos↗

Asbestos-related malignant mesothelioma: growth, cytology, tumorigenicity and consistent chromosome findings in cell lines from five patients.

Seven mesothelioma cell lines were established from clinical specimens from five patients with asbestos-related malignant pleural mesothelioma. The cells in culture show either epithelial or mixed epithelial/fibrosarcomatous growth with an average doubling time of 30 h. Giant multinucleated cells are common in all the cell lines, as well as long thin microvilli on the cell surfaces. All cell lines were cytokeratin positive and they stained negatively for monocyte-macrophage markers. All seven cell lines and one long-term tissue culture from a sixth mesothelioma patient were characterized cytogenetically. Karyotype analyses revealed complex structural and numerical abnormalities, primarily involving chromosome 1, 4, 5, 6, 7, 8, 9, 11, 12, 13 and 22. An excess of chromosome material of the short arm of chromosome 5 was seen consistently in six cell lines and in the long-term culture. In cell lines from four patients, changes in chromosome 13, mainly monosomy 13, were observed. The marker chromosomes observed in the early passages were conserved and few additional changes appeared in later passages. Six of the cell lines tested for tumorigenicity in athymic nude mice were weakly positive.

Adult↗

Clinical significance of IgG subclass antibodies to wheat flour antigens in bakers.

We measured the IgG subclass antibody levels to wheat flour in 42 bakers and 20 controls with an enzyme immunoassay. The levels of total IgG, IgG1 IgG2 and IgG4 antibodies were significantly higher in the bakers than in the unexposed controls. The presence of anti-wheat flour IgG subclass antibodies in the bakers was correlated with various clinical variables including IgE levels, duration of asthmatic or rhinitis symptoms, skin prick test response, peripheral blood eosinophil levels, bronchial histamine reactivity and responses to nasal challenge with wheat flour. The IgG subclass antibody levels of the total cohort of bakers did not correlate with any of the measured clinical variables. However, among men specific IgG4 and IgG1 antibody levels correlated negatively with total IgE levels and duration of rhinitis, respectively. We conclude that IgG and IgG subclass levels to wheat flour in bakers reflect exposure, but that it is not related to any specific clinical situation. The exact pathogenic role of these antibodies in the development of occupational asthma and rhinitis is thus not clear.

Adolescent↗

Quartz-induced production of reactive oxygen metabolites by activated human monocyte-derived macrophages.

Quartz but not titanium dioxide (TiO2) induced the production of reactive oxygen metabolites (ROM) by human monocyte-derived macrophages, as measured by lucigenin dependent chemiluminescence. Activation of the macrophages with BCG, bacterial lipopolysaccharide and macrophage-activating factor (MAF) caused a prominent increase of quartz-induced ROM production, MAF having the strongest effect. The activation did not affect the TiO2 responses to the same extent. Assuming that ROM have a role in the pathogenesis of silica-induced disease in man, we suggest that enhancement of quartz-induced production of ROM by activated pulmonary macrophages may at least partly explain the experimental and epidemiological data indicating that activation of the immune system during infection promotes the development of silicosis.

Humans↗

Mortality and disability among cotton mill workers.

The mortality and disability of cotton mill workers were studied in five Finnish cotton mills. The population under study comprised all 1065 women exposed to raw cotton dust who had been hired between 1950 and 1971. The minimum exposure period was five years. For the study on disability, the cohort was followed up until the end of 1981. The follow up period for the mortality analysis was from 1950 to 1985. At the end of 1981 the observed number of prevalent disability pensions for respiratory disease was 15, whereas 3.9 were expected (p less than 0.01) on the basis of the national figures for women. There were 46 musculoskeletal diseases (27.7 expected, p less than 0.01), of which 24 were osteoarthritis (14.5 expected) and 13 rheumatoid arthritis (6.6 expected). The incidence rates of disability pensions were calculated for the period 1969-81. Comparison of incidence rates between cotton mill workers and the Finnish female population showed excessive rates for both respiratory diseases (p less than 0.001) and musculoskeletal diseases (p less than 0.01), with an excess of new cases of rheumatoid arthritis (p less than 0.05). By the end of 1985 the number of person-years was 31,678 and the number of deaths 95. The standardised mortality ratios for the total period of follow up (1950-85) showed no excess for respiratory diseases. Mortality from cardiovascular diseases was also lower than expected. The observed number of tumours was 33, the corresponding expected number 32.0. Thirteen tumours were in the digestive organs (6.6 expected, p<0.05) and three were lung cancers (1.9 expected). Five workers had died from renal disease; the expected number was 1.5 (p<0.05).

Arthritis, Rheumatoid↗

Concentration of tumor-associated trypsin inhibitor (TATI) in pleural effusions.

We measured the concentration of tumor-associated trypsin inhibitor (TATI) in plasma and pleural fluid of 84 patients with pleural effusions of various causes. We observed elevated (greater than 30 micrograms/L) TATI levels in pleural fluid in 45 percent of patients with pleural effusion associated with malignant disease and in 15 percent of patients with benign disease. Similar results were obtained for TATI in plasma. The concentration of TATI in pleural fluid closely parallelled that in plasma. In patients with renal insufficiency and in patients with biliary obstruction, the TATI levels were elevated both in plasma and pleural fluid. A positive correlation was seen between the concentration of TATI and the activity of alkaline phosphatase in plasma. The results show that simultaneous determination of TATI in plasma and pleural fluid improves the diagnosis of cancer only marginally. Our results also support the hypothesis that elevated TATI levels may reflect an acute phase reaction caused by inflammatory disease or tissue destruction associated with cancer not only in inflammatory conditions, but also in malignant disease where the tumor itself is not producing TATI.

Biomarkers, Tumor↗

Cancer mortality of granite workers 1940-1985.

A retrospective cohort study was undertaken to investigate the cancer mortality of granite workers. The study comprised 1026 workers who took up such work between 1940 and 1971. The number of person-years was 23,434, and the number of deaths was 296. During the total follow-up period, 59 tumours were observed as compared with 54.4 expected. An excess mortality from tumours was observed in workers followed up for 20 years or more. Of the 59 tumours, 31 were lung cancers (expected 19.9), and 18 gastrointestinal cancers (expected 11.6), nine of which were stomach cancers (expected 7.1). Mortality from lung cancer was excessive for workers followed up for at least 15 years (28 observed, 12.7 expected). The results indicate that granite exposure per se may be an etiological factor in the initiation or promotion of malignant neoplasms.

Adult↗

Measurement of reactive oxygen metabolites produced by human monocyte-derived macrophages exposed to mineral dusts.

The aim of the present work was to develop an in-vitro model for studying mineral dust-induced production of reactive oxygen metabolites by human macrophages. Monocytes isolated from human buffy coats were cultured in vitro for 1-6 days. Quartz particles induced both luminol- and lucigenin-dependent chemiluminescence (CL) by the adherent cells. However, the luminol response decreased form day to day, obviously due to a decrease in the myeloperoxidase (MPO) activity of the cells, whereas the lucigenin response showed no such MPO dependence. The luminol response was inhibited by superoxide dismutase (SOD), catalase, and the MPO-inhibitor azide, while the lucigenin response was inhibited by SOD and catalase but stimulated by azide. There was a positive correlation between the lucigenin responses and the results obtained with the established cytochrome c assay for superoxide, when opsonized zymosan was used as a stimulant. The effects of quartz, titanium dioxide, chrysotile asbestos, and wollastonite particles were investigated with the lucigenin assay. Quartz and chrysotile caused prominent light emission by 6-day-old macrophages, whereas titanium dioxide and wollastonite caused weak responses. We conclude that mineral dusts induce production of reactive oxygen metabolites by human monocyte-derived macrophages, and that the quantitative responses depend on both physical and physicochemical dust properties, the nature of which are still to be defined.

Acridines↗

Quartz-dust-induced production of reactive oxygen metabolites by human granulocytes.

We studied the effect of quartz on the production of reactive oxygen species by human polymorphonuclear leukocytes (PMN) in vitro by a chemiluminescence (CL) assay. Quartz caused a rapid dose-dependent CL response in the cells. Diamond dust used as an inert control did not stimulate the production of reactive oxygen metabolite by PMN. The quartz-induced activation of oxygen metabolism was also demonstrated by measuring oxygen consumption, nitroblue tetrazolium reduction, and superoxide and hydrogen peroxide production by PMN. Poly-vinyl-pyridine N-oxide (a quartz surface modifying agent) completely abolished the quartz-induced response, but had no effect on opsonized zymosan-induced CL response of PMN. The effect of N-acetylcysteine (a known antioxidant) was inhibitory to the CL formation induced by both quartz and opsonized zymosan. Our results are in agreement with the hypothesis that quartz-induced production of reactive oxygen metabolites is a possible mechanism by which quartz dust produces chronic inflammation and tissue injury of the lung. Agents interfering with the generation of reactive oxygen metabolites may provide a rationale for treatment of mineral-dust-induced pulmonary disease.

Acetylcysteine↗

Determination of IgG subclass antibodies against wheat flour antigens by an ELISA technique.

We describe the assay conditions for an enzyme-linked immunoassay for the determination of IgG and IgG subclass antibodies in serum to water-soluble wheat flour antigens. The optimal antigen coating concentration was 5 micrograms/ml for total IgG, IgG1, IgG4 and 100 micrograms/ml for IgG2. Serial dilutions of test sera were used and commercially available monoclonal mouse anti-human IgG isotype antibodies (as ascites fluid) were diluted 1:500-1:1000. Specific wheat flour antibodies belonging to the IgG1, IgG2 and IgG4 subclasses were detected. Despite the lack of standardized isotype-specific second mouse monoclonal antibodies, the subclass antibody levels between flour-exposed bakers and controls could be compared. We observed significantly higher IgG1, IgG2, and IgG4 subclass antibodies among 23 bakers than among 12 non-exposed controls, but no IgG3 antibodies were detected. The differences in biological activities of the IgG subclass antibodies may explain the clinical and pathophysiological features for fluor-induced occupational allergic diseases among bakers.

Adolescent↗

IgG and IgA enhance the chrysotile-induced production of reactive oxygen metabolites by human polymorphonuclear leucocytes.

Chrysotile asbestos fibres induce a rapid generation of reactive oxygen metabolites by human polymorphonuclear leucocytes (PMNL) in vitro. This effect was markedly enhanced by the presence of 10-200 micrograms/ml of human gammaglobulin, purified polyclonal IgG, and monoclonal IgG and IgA myeloma proteins. Purified monoclonal IgD, IgM, kappa light chain proteins, and secretory IgA inhibited this chrysotile-induced response. No enhancing effect of IgG was observed when quartz dust or opsonized zymosan were used as stimulators of PMNL metabolism. The enhancing effect of IgG was shown to depend on opsonization of the asbestos fibre. We suggest that the IgG and IgA potentiating effect on the asbestos fibre-induced production of tissue-damaging reactive oxygen metabolites by inflammatory cells is dependent on a particle-specific binding of immunoglobulin to the fibre surface, with subsequent Fc receptor-mediated effects on cells. Such an interaction between certain immunoglobulins and asbestos may explain a number of in vivo phenomena in which immunological responses (hypergammaglobulinemia, circulating immune complexes, etc.) have been shown to relate to the progression of pulmonary asbestosis. The differences between various immunoglobulin classes and monoclonal immunoglobulins could represent an individual inflammation-modulating mechanism in the development of acute or chronic pulmonary asbestosis.

Asbestos↗

The ovarian cancer associated antigen CA 125 in patients with pleural effusions.

The concentration of the ovarian cancer associated antigen CA 125 was determined in the pleural fluid of 25 patients with lung cancer and of 40 patients with benign diseases. Paired serum and pleural fluid samples were measured in 21 tumor patients and 34 patients with nonmalignant diseases. Serum CA 125 was elevated (greater than 35 U/ml) in 16 of 25 (64%) patients with carcinoma and 13 of 34 (38%) patients with benign diseases. The CA 125 level in serum was markedly elevated (greater than 200 U/ml) in five of six adenocarcinomas whereas a slightly elevated level was associated with only one of four mesotheliomas and with one of three secondary carcinomas. The pleural fluid concentration of CA 125 was higher than the serum value in 90% of the patients, showing a median ratio of 4.9, respectively. Pleural fluid values higher than 250 U/ml were seen in 18 of 25 (72%) subjects with pleural effusion due to malignancy and in 10 of 40 (25%) patients in the benign group. There were no apparent differences in the pleural fluid CA 125 levels in patients having different types of cancer and different benign diseases.

Adenocarcinoma↗