Search PubMed⌕ Search

Biomedical subjects

T Tuomi

Publications and source records attributed to T Tuomi.

At least 91 records · Page 5Linked to original sources

Gap junctional intercellular communication of primary and asbestos-associated malignant human mesothelial cells.

We examined gap junctional intercellular communication (GJIC) of primary human mesothelial cells and cell lines of asbestos-associated human pleural mesotheliomas, and the effect of asbestos and other mineral fibres on these cells. In homologous cultures, the GJIC capacity of six out of seven tumour cell lines was markedly less than for primary mesothelial cells. This defect in GJIC appeared not to be at the expression level of mRNA and protein of the gene encoding the 43 kDa gap junction protein. In heterologous cocultures of tumour cells and primary mesothelial cells, however, 80-90% of the tumour cell/normal cell contacts were functional. Exposure of primary mesothelial cells to TPA, a phorbol ester tumour promoter, resulted in marked inhibition of GJIC, being an action common to numerous tumour promoters. Such an effect though was not observed with the carcinogenic mesothelioma-inducing mineral fibres chrysotile and amosite, neither with glass wool. These results suggest that a permanent defect in GJIC capacity is a common feature of human mesothelioma cells, but how mineral fibres are involved in the process of mesotheliomagenesis is still unclear.

Asbestos↗

Hypersensitivity pneumonitis and exposure to zirconium silicate in a young ceramic tile worker.

We describe a nonsmoking ceramic tile worker 25 yr of age who developed a worsening dry cough and dyspnea after 3.5 yr as a sorter and glazer of tiles. Open lung biopsy revealed an intense granulomatous interstitial pneumonia with mild fibrosis, compatible with hypersensitivity pneumonitis, and numerous very small birefringent crystals around the terminal airways and occasionally in granulomas. Pulmonary particle analysis revealed an inhaled dust burden nearly 100-fold the normal background level, mainly consisting of clay minerals and zirconium silicate. The patient had no history or clinical or laboratory findings suggesting any organic etiologic agent. A sarcoid granulomatosis type of chronic pulmonary hypersensitivity reaction is known after long-term exposure to zirconium, but this case demonstrates that zirconium can also cause an acute and fulminant allergic alveolitislike hypersensitivity reaction.

Adult↗

Antibodies to glutamic acid decarboxylase in Australian children with insulin-dependent diabetes mellitus and their first-degree relatives.

Antibodies to glutamic acid decarboxylase (GAD), previously known as the 64-kD pancreatic islet cell autoantigen, are an important serologic marker of insulin-dependent diabetes mellitus (IDDM). Antibodies to GAD (anti-GAD) were examined in sera from Australian children with newly diagnosed IDDM (within 1 mo of diagnosis), IDDM of longer duration (mean +/- SD, 4.8 +/- 3.3 y), and in first-degree relatives, using a radioimmuno-precipitation assay with purified porcine brain GAD as antigen. Antibodies to islet cell cytoplasmic antigens (ICAb) were tested concurrently. The frequency of anti-GAD was not significantly different in children with newly diagnosed IDDM (31 of 42, 74%) and with IDDM of longer duration (14 of 21, 67%), whereas ICAb were present more frequently in children with newly diagnosed IDDM (64%) than in those with longer duration IDDM (14%). In all, 90% of children with newly diagnosed IDDM had either anti-GAD or ICAb, whereas only 48% had both. For the 77 first-degree relatives, the frequency of anti-GAD was 2% (one of 44) in parents and 6% (two of 33) in siblings; ICAb were not detected in any of these relatives. The presence of anti-GAD in the majority of children with IDDM, irrespective of the duration of their disease, represents a useful diagnostic marker for IDDM, and should be of value in ascertaining individuals at risk for developing IDDM.

Adolescent↗

Antibodies to glutamic acid decarboxylase reveal latent autoimmune diabetes mellitus in adults with a non-insulin-dependent onset of disease.

The classification of adults with diabetes mellitus can be invalidated by patients who initially present as NIDDM but who later become frankly insulin dependent. In some of these, the pathogenesis could be similar to that in IDDM, namely autoimmune destruction of the pancreatic beta-cells. We studied 102 patients > 35 yr of age at diabetes onset who had initially been nonketotic and non-insulin-dependent for > or = 6 mo. They were classified according to glucagon-stimulated C-peptide levels into an insulin-deficient group (n = 33) and a non-insulin-deficient group (n = 69). We measured antibodies to GAD, islet cell cytoplasm, thyroid antigens, and gastric parietal cells in both groups. Anti-GAD was significantly higher in the insulin deficient group, 76% (25 of 33), than in the non-insulin deficient group, 12% (8 of 69), and this difference was substantially greater than that shown for ICAs. Thus, in a proportion of adults who present with NIDDM, a slowly evolving autoimmune insulitis can be revealed by testing for anti-GAD. This could have important connotations not only for early intervention, but also for the correct classification of diabetes.

Adult↗

Fibrous minerals in the lungs of mesothelioma patients: comparison between data on SEM, TEM, and personal interview information.

To determine and compare the fiber types and size distributions in the lung tissue of mesothelioma patients in Finland, samples from 29 patients with known work history were analyzed with transmission electron microscopy (TEM) and X-ray microanalysis. Compared with the earlier results using scanning electron microscopy (SEM), the fiber concentrations were about three times as high and ranged from 0.1 million to 5,200 million fibers per gram of dry tissue. In 15 patients (52%), crocidolite/amosite were the dominating fiber types, representing more than 70% of all fibers. Anthophyllite asbestos was the most prevalent fiber type in eight patients (28%), and it was found in the samples of 13 patients (45%). One-half of the anthophyllite fibers were longer than 5 microns, whereas other fiber types were somewhat smaller.

Adult↗

Malignant mesothelioma: clinical characteristics, asbestos mineralogy and chromosomal abnormalities of 41 patients.

The clinical characteristics and the results of mineral fibre and cytogenetic analyses were coordinated prospectively for 41 patients with confirmed malignant pleural mesothelioma. A correlation was found between high total fibre concentration, and partial or total loss of chromosomes 1, 4 and 9 and chromosomal rearrangements involving a breakpoint at 1p11-p22. There was also a correlation between crocidolite/amosite as the main fibre type and partial or total loss of chromosomes 1, 3 and 4 and chromosomal rearrangements involving del (3p). Positive prognostic factors were female gender, low total fibre concentration (less than 10(6) fibres per g dried lung tissue), anthophyllite as the main fibre type and normal chromosome 7. In addition, we found 4 patients with malignant mesothelioma who had been exposed mainly to anthophyllite fibres (total lung fibre concentrations of 1.2, 0.4, 0.2 and 0.1 x 10(6) fibres per g dried lung tissue). This would seem to indicate that there may be a carcinogenic role for anthophyllite.

Adult↗

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↗

Occupational exposure to asbestos as evaluated from work histories and analysis of lung tissues from patients with mesothelioma.

The past occupational exposure to asbestos of 23 patients with mesothelioma (21 men and two women) has been evaluated by a personal interview of their work history and by determination of the fibre burden in their lung tissue with scanning electron microscopy (SEM) and x ray microanalysis. According to the work history, nine patients (39%) had definitely been or probably been exposed to asbestos, six patients (26%) had had possible exposures, and eight patients (35%) unlikely or unknown exposure to asbestos. The two female patients were in the unknown exposure category. The fibre concentrations in the patients' lung tissue ranged from less than 0.1 million to 370 million fibres (f) per g dry tissue. Concentrations of over one million f per g dry tissue were found in 15 patients (65%). The lung fibre concentrations of all nine male office workers analysed for reference were less than one million f per g dry tissue. Seventy eight per cent of the patients with mesothelioma had at least possible exposure according to their history of work or concentrations of more than one million f per g dry tissue.

Adult↗

Relative risk of mesothelioma associated with different levels of exposure to asbestos.

The relative risk of mesothelioma associated with different levels of exposure to asbestos was evaluated. The exposure was assessed from work histories of 51 mesothelioma cases and 51 sarcoidosis referents. The lung fiber concentration of the mesothelioma patients was compared with that of two reference groups (13 random autopsy cases and 43 male lung cancer patients). When the categories definite and probable were used as an estimated probability of occupational exposure, an odds ratio of 17.7 [90% confidence interval (90% CI) 3.4-253] and 3.0 (90% CI 0.9-10.6), respectively, was obtained. A lung fiber concentration of greater than 1 million fibers/g of dry tissue as an indicator of accumulated exposure gave an odds ratio of 14.4 (90% CI 2.5-178) for the men in comparison with the autopsy cases and 3.1 (90% CI, 1.3-7.5) in comparison with the lung cancer patients. Elevated risk of mesothelioma was shown to be associated with a lung fiber concentration of greater than 1 million fibers/g of dry tissue.

Adult↗

Rheumatoid factors antedating clinical rheumatoid arthritis.

The relationship between rheumatoid factors (RF) and rheumatoid arthritis (RA) was studied in the Mini-Finland Health Survey. This covered a representative sample of the Finnish population over 30 years of age, initially comprising 8,000 persons, of whom 7,217 participated in the field survey carried out in 1978-80. The participants were followed using record linkage with the Social Insurance Institution's population register to identify patients entitled to free medication. Until the end of 1988, 21 persons had developed new seropositive RA. In 15 cases, preillness specimens contained elevated levels (greater than or equal to 20 IU/ml) of RF. In the remaining 6 cases with RF negative preillness specimens, the interval from taking the blood specimen to the onset of disease was 4 years or more. RF represent a key element in the rheumatoid inflammatory process. Their occurrence in preillness specimens suggests that they may have a primary role in the pathogenesis of the disease.

Adult↗

Measuring rheumatoid factor in nonrheumatoid subjects: immunoturbidimetric assay, latex slide test, and enzyme-linked immunosorbent assay compared.

Previous studies of patients with rheumatoid arthritis (RA) have shown a good correlation between results from immunoturbidimetric assays of rheumatoid factor (RF) and latex fixation tests. To extend the research to non-RA subjects, we tested sera from 1000 pregnant women, half each in the first and third trimesters. By turbidimetry, 24 non-RA sera were regarded as positive for RF (greater than or equal to 20 int. units/mL) and 18 sera as borderline (15-19 int. units/mL). By the latex fixation test, 28 non-RA sera gave a clear reaction (positive) and 17 sera a weak reaction (borderline). The association between the tests was statistically highly significant (P less than 0.001). All sera with positive and borderline reactions were tested by enzyme-linked immunosorbent assay for RF isotypes, together with a random subsample of about one-sixth of the original serum samples. Positive RF results by immunoturbidimetry were predominantly due to the presence of IgM-RF. In contrast to some earlier findings, we saw no difference in the prevalence of positive RF reactions between sera from the first and third trimesters.

Enzyme-Linked Immunosorbent Assay↗

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↗

Smoking, lung function, and rheumatoid factors.

Positive rheumatoid factor (RF) reactions commonly precede the onset of clinically manifest rheumatoid arthritis (RA). Thus if items associated with RF reactions were traced at the community level this might provide clues to the cause of RA. The relations between smoking and lung functions and the occurrence of RA and RFs in a population sample representative of the adult Finnish population were studied. Rheumatoid factor testing was performed for 7124 subjects (89% of the sample) by the sensitised sheep cell agglutination test. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were measured with spirometry. 'False positive' RF reactions occurred twice as often in current smokers and ex-smokers than in those who had never smoked. The prevalence of high titres was fourfold greater among current smokers than among those who had never smoked. These associations were statistically significant and independent of age, FVC, and FEV1 in both sexes. The women with airflow limitation (FEV1/FVC less than 70%) had a significantly increased occurrence of RFs which was independent of their smoking history, but no such relationship was found in men. The results suggest an impact of smoking on RF production; a follow up study may show whether the raised RF titers in smokers will be reflected as an increased incidence of RA.

Adult↗

Mineral fiber concentration in lung tissue of mesothelioma patients in Finland.

The mineral fibers in lung tissue samples of 19 mesothelioma patients and 15 randomly selected autopsy cases were analyzed using low-temperature ashing, scanning electron microscopy (SEM) and x-ray microanalysis. The fiber concentration ranged from 0.5 to 370 million fibers per gram of dry tissue in the mesothelioma group and from less than 0.01 to 3.2 million fibers per gram of dry tissue in the autopsy group. In 80% of the mesothelioma patients and in 20% of the autopsy cases, the fiber concentration exceeded 1 million fibers per gram of dry tissue. Amphibole asbestos fibers predominated in both groups, and only a few chrysotile fibers were found. In the lungs of six mesothelioma patients, anthophyllite was the main fiber type. The overall analytical precision of sample preparation and fiber counting with SEM was 22%.

Adolescent↗

Chromosomal abnormalities and their correlations with asbestos exposure and survival in patients with mesothelioma.

Cytogenetic findings of our 30 previously reported and eight new patients with malignant pleural mesothelioma were summarised and correlated with asbestos fibre burden in lung tissue and survival. Successful cytogenetic analyses were performed on cells obtained from the tumours and/or pleural effusions of 34 of the 38 patients. Clonal chromosomal abnormalities were detected in 25 patients, 19 of them studied before treatment. Nine patients, seven of them studied before treatment, had normal karyotypes and/or non-clonal chromosomal abnormalities. Most of the karyotypic findings in the patients with clonal abnormalities were complex and heterogeneous, and no chromosome aberration specific to mesothelioma could be demonstrated. The following numerical abnormalities in decreasing order of frequency were preferentially present in karyotypic changes: -22, +7, -1, -3, -9, +11 and -14 (-/+ denoting partial or total loss or gain). Translocations and deletions involving a breakpoint at 1p11-p22 were the most frequent structural aberrations. Statistically significant correlations were found between high content of asbestos fibres in lung tissue and partial or total losses of chromosomes 1 and 4, and a breakpoint at 1p11-p22 (P = 0.0001, P = 0.003, P = 0.009, respectively). The number of copies of chromosome 7 short arms was inversely correlated with survival (P = 0.02). In this study no diagnostic cytogenetic markers of mesothelioma were found, instead the copy number of chromosome 7 short arms turned out to be a possible prognostic factor in malignant mesothelioma.

Adult↗

Pilot study on obesity in caries prediction.

The aim of the present study was to explore the possibility of predicting the incidence of dental caries from obesity. The subjects were 516 children living in Luvia, Finland, born between 1972 and 1981. Obesity alone was not a very good predictor of dental decay. When predicting caries in the permanent first molars using both earlier obesity and earlier caries experience as predicting indicators, 65-70% of the true risk group was identified. This combination was even better for the prediction of caries in permanent second molars.

Adolescent↗