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Biomedical subjects

K Tuomi

Publications and source records attributed to K Tuomi.

At least 37 records · Page 2Linked 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↗

Symptoms of mental and physical stress in different categories of municipal work.

The aim of this study was to clarify the stability of differences in reactions to work stress in different municipal occupations. The subjects were 1799 men and 2456 women in the same occupation in 1981 and 1985. At the time of the follow-up in 1985 their age range was 48-62 years. On the basis of the work content, they were clustered into 13 profile groups. Long-term cardiorespiratory, musculoskeletal, and psychological symptoms and symptoms indicating immediate physical stress at work were used to measure stress reaction. The order of the profile groups with respect to harmful stress reactions was the same in both years. According to the first and also the follow-up questionnaire, harmful stress reactions were the most common in physical work and in some profile groups with mixed physical and mental work demands. Although these differences were the greatest for the reactions to physical stress, they were also seen for mental stress.

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↗

Induction of cytochrome P450IA1 in mouse hepatoma cells by several chemicals. Phenobarbital and TCDD induce the same form of cytochrome P450.

The mouse hepatoma cell line Hepa-1 was studied for aryl hydrocarbon hydroxylase (AHH) inducibility by sixteen compounds known to be inducers of cytochrome P450 of different "classes". Both 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and sodium phenobarbital induced AHH activity. A cytochrome P450IA1-specific (P1-450) mouse cDNA probe was used to quantitate mRNA induction. There was a good correlation between the amount of cytochrome P450IA1 mRNA induced and AHH activity. Immunoblots with monoclonal antibody 1-7-1, which recognizes rat liver P450IA1 and P450IA2 (P450c and P450d, respectively), showed that both phenobarbital and TCDD increase the amount of a P450 isozyme immunorelated to P450IA1 in this cell line. Hepa-1 mutants with no AHH inducibility (no functional P450IA1 structural gene; no Ah receptor; no nuclear translocation of the inducer-receptor complex; and presence of dominant repressor) did not respond to phenobarbital. The cytosolic receptor for TCDD (Ah receptor) was characterized to see if phenobarbital induced cytochrome P450IA1 mRNA and the hydroxylase enzyme through the same mechanism as TCDD. 20 mM Phenobarbital almost completely abolished the binding of 3H-TCDD to the cytosolic receptor. These data indicate that phenobarbital can be a weak ligand for the Ah receptor and thus induce cytochrome P450IA1 and AHH activity. The observation increases the list of different P450 forms inducible by phenobarbital.

Animals↗

2-(4'-chlorophenyl)benzothiazole is a potent inducer of cytochrome P450IA1 in a human and a mouse cell line. Anomalous correlation between protein and mRNA induction.

Two benzothiazole derivatives, 2-(4'-chlorophenyl)benzothiazole (CPBT) and 2-(4'-formylphenyl)benzothiazole (FPBT) were studied for their ability to induce aryl hydrocarbon hydroxylase activity in a mouse and a human cell line. In both the mouse hepatoma cell line, Hepa-1, and the human choriocarcinoma cell line, JEG-3, a high aryl hydrocarbon hydroxylase activity was observed after treatment with CPBT. In contrast, FPBT had a very weak inducing capacity in both cell lines. The maximal induction by CPBT was several times (e.g. in Hepa-1 about fourfold on average) greater than that observed with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). A specific cDNA probe for mouse cytochrome P4501A1 gene was used to quantify mRNA levels in Hepa-1 cells. CPBT increased cytochrome P450IA1 mRNA to a level of 88% of that induced by TCDD. Immunoblot analysis with monoclonal antibody 1-7-1, directed against rat liver cytochrome P450IA1 and P450IA2, showed that the amount of P450IA1 is substantially increased in Hepa-1 cells after treatment with CPBT. The observation that CPBT competed TCDD off its specific cytosolic binding site suggests a receptor-mediated induction of cytochrome P450IA1 mRNA. An in vitro activation effect did not explain the exceptionally high hydroxylase activity. The results show that CPBT is a more efficient inducer of aryl hydrocarbon hydroxylase than TCDD in Hepa-1 and JEG-3 cells and that the induction is supported by P450IA1. The discordant effect of CPBT on mRNA and aryl hydrocarbon hydroxylase activity suggests that post-translational modifications of P450IA1 account for a major part of the increased enzyme activity.

Animals↗

Complaints of insomnia in different occupations.

Complaints of insomnia were inquired about in a questionnaire survey of 6 268 persons (2 801 men; 3 467 women, mean age 50.5 years, range 45-57 years) in 40 different occupational groups. Among bus drivers 18.9% complained of having rather or very much difficulty falling asleep. Among female cleaners, male teachers, male directors, and male physicians the respective percentages were 18.8, 18.0, 3.7, and 4.9. Disturbed nocturnal sleep was complained of the most often by male laborers (28.1% waking up at least three times a night), female cleaners (26.6%) and female hospital aides (26.4%). Disturbed nocturnal sleep was rare among male physicians (1.6%), male directors (7.4%), female head nurses (8.9%), and female social workers (9.4%). Complaints of waking up too early in the morning were the most common among female laborers (13.2% often or always), male construction workers (9.1%), and female cleaners (8.4%). They were rare among male physicians (1.6%), male directors (1.8%), nurses in outpatient wards (1.2%), and female bathers (2.0%). Sleeping pills were used the most frequently by male gardeners (7.1% were frequent or habitual users), female social office workers (5.8%), and male construction workers (5.4%). Some aspects of work which could explain the differences are discussed.

Female↗

Disproportionate synthesis of Semiliki Forest virus 42S and 26S RNAs in polyamine-depleted baby hamster kidney cells.

The role of polyamines in viral RNA synthesis has been studied using Semliki Forest virus-infected, polyamine-depleted baby hamster kidney cells as a model system. The synthesis of viral 42S RNA, which corresponds to the viral genome, was markedly inhibited, while the synthesis of viral 26S RNA, which acts as a messenger for viral structural proteins, was reduced much less or not at all. The decreased total viral RNA synthesis and the ratio of 42S to 26S RNA were rapidly returned to normal by adding spermidine to the culture medium. From these results it can be hypothesized that polyamines have a special role in the synthesis of viral RNA, possibly affecting the conformation of the RNA template.

Animals↗

Synthesis of Semliki-forest virus in polyamine-depleted baby-hamster kidney cells.

The role of polyamines in macromolecular synthesis has been studied using the synthesis of Semliki-Forest virus (SF virus) in normal and alpha-difluoromethylornithine-treated baby-hamster kidney (BHK21) cells as a model system. The activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase, the rate-limiting enzymes in polyamine biosynthesis, decreased rapidly in mock- and SF-virus-infected cells, indicating that virus production in BHK21 cells was not dependent on polyamines formed after infection. A prolonged treatment of BHK21 cells with alpha-difluoro-methylornithine, a specific inhibitor of polyamine synthesis, resulted in a marked inhibition of the initial rate of virus production, which appeared 72 h after the beginning of the treatment. This inhibition was reversed by putrescine, spermidine and spermine, and at last partially by several other diamines and polyamine homologues. Polyamine-depletion also markedly reduced viral RNA polymerase activity in SF-virus infected cells. Addition of spermidine to the culture medium rapidly increased viral RNA polymerase activity in the inhibitor-treated cells but had no effect on the enzyme activity when added directly to the assay mixture. The results indicated that polyamines are needed for maximum initial rate of SF-virus replication and suggest that the inhibition of virus production in polyamine-depleted cells is at least partly due to malfunction of the protein-synthetic machinery of the host cell.

Animals↗

Inhibition of the synthesis of polyamines and macromolecules by 5'-methylthioadenosine and 5'-alkylthiotubercidins in BHK21 cells.

5'-Methylthioadenosine and four 5'-alkylthiotubercidins were tested for their ability to inhibit polyamine synthesis in vitro and to decrease polyamine concentration and prevent growth of baby-hamster-kidney (BHK21) cells. 5'-Methylthioadenosine and 5'-methylthiotubercidin decreased the activity of spermidine synthase from brain to roughly the same extent, whereas brain spermine synthase was much more strongly inhibited by 5'-methylthioadenosine compared with 5'-methylthiotubercidin. These nucleoside derivatives also inhibited the growth of BHK21 cells and increased the concentration of putrescine. 5'-Methylthioadenosine decreased cellular spermine concentration, whereas 5'-methylthiotubercidin lowered the concentration of spermidine. The activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase were enhanced in cells grown in the presence of 5'-methylthiotubercidin. The growth inhibition produced by these nucleoside derivatives was not reversed by exogenous spermidine or spermine. 5'-Ethylthiotubercidin, 5'-propylthiotubercidin and 5'-isopropylthiotubercidin did not appreciably inhibit spermidine or spermine synthase in vitro or decrease the cellular polyamine content, but effectively prevented the growth of BHK21 cells. All nucleoside derivatives at concentrations of 0.2-1 mm caused a rapid inhibition of protein synthesis. It is concluded that the growth inhibition produced by 5'-methylthioadenosine and 5'-alkylthiotubercidins was not primarily due to polyamine depletion but other target sites, for instance the cellular nucleotide pool, cell membranes etc. must be considered.

Adenosine↗

Uptake and utilization of 5'-methylthioadenosine by cultured baby-hamster kidney cells.

5'-Methylthioadenosine was taken up and immediately metabolized further by cultured baby-hamster kidney cells during the exponential phase of growth. The adenine moiety supplied the purine-nucleotide pool via the salvage pathway and was efficiently incorporated into nucleic acids. Catabolites of methylthioadenosine excreted by the cells included adenine, purinic compounds and metabolites of the ribose portion. 5'-Methylthiotubercidin had no significant effect on the cellular metabolism of methyl-thioadenosine, but greatly inhibited its uptake. erythro-9-(2-Hydroxy-3-nonyl)adenine had no effect on the uptake, but markedly interfered with the further utilization of methylthioadenosine after cleavage in the cells.

Adenine↗

Roles of polyamines in the replication of animal viruses.

Several animal viruses are known to contain significant amounts of polyamines but so far the function of these viral components is poorly understood. In this study the role of polyamines in the replication of two different types of viruses, herpes simplex virus type 2 and Semliki Forest virus (SFV) has been investigated. Purified SFV was found to contain fairly small amounts of polyamines, sufficient to neutralize only about 3% of viral nucleic acid phosphate, i.e., 1/20 of that found in herpes simplex virus. The production of both viruses was, however, markedly inhibited in BHK21 cells depleted of polyamines by treatment with alpha-difluoromethylornithine, a specific inhibitor of polyamine synthesis. This inhibition was reversed by putrescine, spermidine and spermine, and at least partly reversed by several other diamines and polyamine homologs. The activity of viral RNA polymerase induced by SFV infection was markedly reduced in polyamine-depleted cells but increased rapidly after addition of spermidine to the culture medium. It appears that the inhibition of virus production in polyamine-depleted cells is due in part to malfunction of protein synthetic machinery of the host cell. The possibility that other steps in virus synthesis and assembly are affected by polyamine deficiency is currently being investigated.

DNA-Directed RNA Polymerases↗

Quantitation of Semlike Forest virus RNAs in infected cells using 32-P equilibrium labelling.

In vitro cultured BHK and HeLa cells were labelled for several cell division cycles with 32-P-phosphate until they were equilibrated with radiophosphorus. After infection with Semliki forest virus (or mock-infection) these cells were analyzed for viral and ribosomal RNA by sucrose gradient centrifugation. From their radioactivities the mass of each RNA species was calculated. It was found that the BHK and HeLa cells contained on average 11.0 plus or minus 3.1 pg and 6.3 plus or minus 1.9 pg of ribosomal RNA (28 S + 18 S) respectively per cell. At the end of the viral growth cycle, i.e. at 8 h post infection the average mass of viral genome produced per cell was 1.0 -1.9 pg and 0.3 - 0.5 pg in BHK and HeLa cells respectively, of which only 1/10 to 1/20 was released as mature virus particles. The amount of the second major virus specific messenger, the 26 S RNA, was estimated from its ratio to the viral genome after labelling with 3-H-uridine in the presence of actinomycin D. These two viral RNAs were found to be present in roughly equimolar amounts.

Animals↗

Replication of Semliki Forest virus.

Replication of Semliki Forest virus, a typical alphavirus, takes place in the cytoplasm of many eukaryotic cells. The virus genome, the 42 S RNA, directs the synthesis of at least two RNA-dependent RNA polymerases. By the aid of these enzymes complementary 45 S RNA is synthesized; it serves as a template for the synthesis of positive RNA strands with sedimentation values of 45 S and 26 S. In BHK cells close to 200,000 molecules of each RNA species are produced per cell. Both 26 S and 42 S RNAs are associated with polysomes synthesizing viral structural proteins. The 26 S RNA is a duplication of the nucleotide sequences coding for the virion proteins. These are translated as a polyprotein with the capsid protein at the N-terminal end followed by the envelope proteins E2 and E1. Usually only small amounts of nonstructural proteins are synthesized at the exponential phase of virus growth, indicating that a translational control operates in Semliki Forest virus-infected cells. One of our temperature-sensitive mutants, ts-1, directs, however, the synthesis of two nonstructural proteins with MWs of 78,000 and 86,000 when grown at the nonpermissive temperature. The assembly of the viral nucleocapsid begins by association of the capsid protein with the 42 S RNA, which is still serving as a messenger. In this process a cytoplasmic structure sedimenting at about 65 S is presumably one of the capsid protein donors. The 140 S nucleocapsid buds through the host cell plasma membrane whereby the capsid protein interacts with the envelope proteins creating a specific viral envelope devoid of host proteins. Altogether 5,000 to 20,000 virus particles are released from each cell by the end of the growth cycle, representing about 10% of the 42 S RNA molecules synthesized during the infection.

Animals↗

Work ability and job demands of aging white- and blue-collar workers in 1981 and 1996.

This study compared perceived work ability and job demands in 1981 and 1996. Two samples of municipal workers were formed by matching according to location (eastern Finland), occupational status (white- and blue-collar jobs), gender (men), and age (> or = 45 years). In 1981, 50 white-collar (mean age 51 [SD 3] years) and 214 blue-collar (mean age 51 [SD 4] years) workers responded. In 1996, the corresponding numbers were 43 and 54, respectively, the mean age being 50 [SD 4] years for both groups. Perceived work ability and psychological resources changed very little from 1981 to 1996, but there seemed to be a trend towards a more positive view of future work ability. General and mental job demands, in particular, seemed to be increasing among white-collar workers. The observed differences in work ability and job demands were systematically more positive among blue-collar workers than among the white-collar workers.

Aging↗