Estimation of individual dust exposure by magnetopneumography in stainless steel production.

The objectives of the study were to measure the magnetic dust lung burden of workers in stainless steel production by magnetopneumography (MPG) and to investigate the relationship of the results with air-borne concentrations of dust, total and hexavalent chromium as well as urinary excretion of chromium. There were 128 workers from the chromite mine, sintering plant, ferrochrome smelter, stainless steel smelting shop, cold rolling mill and welding shop in the exposed groups and five persons from the office staff in the control group. The remanent magnetic field (RMF) in the lungs was slightly elevated among workers in the ferrochromium and steel smelting shops; the levels were, however, lower than those reported for welders earlier and those observed in the welding/repair shop. Workers in the mine, concentrator and sintering plants and in the cold rolling mill exhibited remanent magnetic fields comparable to the referents. There was a relationship between the RMF and the actual urinary chromium concentration. Miners and concentrator and sintering plant workers showed retarded relaxation rate (ReR) of the remanent magnetic field. However, the RMF of the first two of these groups were low (< 0.1 nT) and this made it difficult to measure the ReR accurately. The duration of exposure correlated weakly but significantly with the relaxation rate, while smoking was not related to it.

Bacillus Calmette-Guérin sensitises fresh transitional carcinoma cells and T24 cell line to non-MHC-restricted cytotoxicity in vitro.

The activity of lymphokine (interleukin-2) activated killer (LAK) cells from 9 patients with transitional cell carcinoma (TCC) was tested against autologous, freshly purified transitional carcinoma cells. Cytotoxicity was relatively low. Bacillus Calmette-Guérin (BCG) substantially augmented both LAK activity and the cytolytic activity of non-stimulated peripheral blood mononuclear cells (PBMC) against autologous TCC when tested with 6 additional TCC patients. A similar enhancing effect of BCG was noted with leucocytes obtained from normal donors when tested against an allogenic T24 cell line. Both natural killer (NK) cells and T cells appeared to be responsible for the increased cytolytic activity caused by BCG. No cytolytic activity was noted against normal transitional epithelial cells. Sensitisation of TCC cells to the immune system may explain the clinical effects of BCG.

Effects of recombinant alpha-2b-interferon therapy in patients with progressive MS.

The effects of systemic recombinant interferon-alpha-2b were studied in 6 carefully selected patients with progressive multiple sclerosis. 3.0 million IU were given as daily subcutaneous injections for 6 months, 5 patients showed worsening disability, and in 4 of them new or enlarged lesions were detected in MRI. In one patient no change in disability was found; his MRI showed regressed changes. The mean progression index during the treatment was significantly higher (p < 0.02) than during the previous 2 to 3 years' period of continuous progression. The frequency of peripheral blood natural killer (CD16+) cells declined significantly 3 months during the treatment, but returned to the pretreatment values after termination the treatment. An increase of intrathecal IgG synthesis and oligoclonal bands was demonstrated in 4 and 3 patients, respectively. Our experience suggests that long-term recombinant IFN-alpha-2b treatment may activate the immunological process of MS.

Recognition of chromosome 6-associated target structures by human lymphokine-activated killer cells.

Different populations of unstimulated and IL-2-activated PBL were used in binding and killing assays against somatic mouse/human lymphocyte cell hybrids containing different human chromosomes. Unstimulated PBL effector cells showed low binding and killing activity to both cell hybrids and mouse parental cell lines. However, IL-2-activated killer (LAK) cells bound strongly to, and effectively killed, cell hybrids carrying human chromosome 6, but were inefficient in both assays to mouse parental cells and to cell hybrids not carrying human chromosome 6. These results show that human LAK cells but not endogenous NK cells bind and kill mouse/human lymphocyte hybrids containing human chromosome 6. We thus suggest that LAK cells recognize ligands encoded by genes on chromosome 6.

Damage to multicellular human H-2 glioma spheroids incubated with LAK cells: an ultrastructural study.

Local brain tumor therapy using lymphokine-activated killer (LAK) cells and recombinant interleukin-2 (rIL-2) has not proved to be effective in preliminary clinical trials. One obstacle to effective use of this therapy is ignorance about the events that follow contact of the LAK cells with glioma tissue. We used multicellular spheroids grown from human glioma cell lines as targets to study, in vitro, the effect of LAK cells against three-dimensional glioma tissue. Here we describe the ultrastructural changes in spheroids of H-2 glioma cells incubated in pellets of LAK cells for up to 24 hours. In H-2 spheroids, cellular damage was not restricted to the effector cell-target cell (effector-target) contact; it extended farther, at least partly because of nonspecific changes in the spheroid micromilieu. Formation of cytoplasmic blebs, a characteristic effect of T cells, natural killer cells, and LAK cells on single target cells, also occurs in H-2 spheroids, and it is not limited to the effector-target contact area either. These findings suggest that LAK cells release membrane-damaging agents that remain active outside the effector-target area, in the micromilieu of H-2 spheroid tissue.

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.

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.

Effect of LAK cells against three-dimensional tumor tissue. In vitro study using multi-cellular human glioma spheroids as targets.

The anti-tumor mechanisms of local LAK cell therapy are difficult to study in vivo. We describe a method to study in vitro the action of LAK cells against three-dimensional tumor tissue. Spherical cell aggregates (spheroids) grown from human glioma cell lines H-2 and U-251 were labeled with 51Cr and then incubated for up to 24 h with LAK cells. After the incubation, most spheroids were still macroscopically identifiable, and the measured reduction of volume did not correlate to the extent of damage. LAK cells infiltrated into spheroid tissue slowly as a frontier which explains why the specific 51Cr release was clearly slower from spheroids than corresponding single cell suspensions. The infiltrated area was at 1 to 2 h very thin but by 8 to 12 h consisted already of several cell layers. Most H-2 spheroids became totally infiltrated by 16 to 24 h whereas in U-251 spheroids the infiltration usually remained peripheral. In accordance with the different extent of infiltration, H-2 spheroids were clearly more sensitive to LAK cells than U-251 spheroids: at E/T ratio 10:1 the mean specific 51Cr release by 24 h was 63 and 36%, respectively. A single exposure to LAK cells released 51Cr from H-2 spheroids approximately 12 h but over 24 h from U-251 spheroids. The spheroid model can be used to study the infiltrative capacity and cytotoxicity of LAK cells against three-dimensional tumor tissue, and the method may help to find an optimal mode of local LAK cell therapy, i.e., proper combination of lymphokines and LAK cells, and proper timing of their administration.

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.

Incidence of cancer among welders, platers, machinists, and pipe fitters in shipyards and machine shops.

The incidence of cancer in 12,693 shipyard and machine shop male workers (1689 welders, 4308 platers, 6003 machinists, 693 pipe fitters) employed for at least one year between 1945 and 1960 was investigated in a retrospective cohort study. The welders had welded only mild steel and had not been exposed to hexavalent chromium containing fume. The follow up was 99.7% complete and the total number of person-years was 304,682. The incidence of cancer in 1953-81 was ascertained through the Finnish Cancer Registry. The observed numbers of cases of cancer were compared with the expected numbers based on regional urban rates. The smoking habits of the cohort were surveyed with a postal questionnaire sent to a sample of 961 workers. The smoking habits of the cohorts were similar and smoking was not more common than among the general population. The total number of cases of cancer was 611 (exp 629) among the shipyard workers and 376 (exp 388) among the machine shop workers. The incidence of lung cancer was increased among the shipyard workers (obs 227, exp 192). This excess was observed in all the worker groups and was most evident for the pipe fitters and platers. Among the machine shop workers, the incidence of lung cancer was lower than expected with the exception of the welders who had a slightly raised risk of lung cancer (obs 14, exp 10). The incidence of laryngeal cancer was slightly raised among the shipyard workers (obs 24, exp 20) but not in the machine shop workers. No excess risk was observed among the welders. The incidence of cancer of the prostate was increased among the machine shop workers (obs 39, exp 31) but not in the shipyard workers. The excess was statistically significant for the welders. No pronounced excess could be found for other types of cancer. Analysis by the duration or exposure showed that the excess of lung cancer in the shipyard workers was most evident during the last period of observation (1972-81). No other trends were obvious and the slight excess of lung cancer observed among the welders did not increase with increasing follow up time. No excess risk for mesothelioma was found. The small excess of lung cancer in welders could be due to chance. The fact that only a small and statistically insignificant excess of lung cancer could be found among this group of heavily exposed welders suggest that if the risk of lung cancer was associated with welding this risk must nowadays be low and probably too low to be unequivocally detected in most epidemiological studies.

Cyst fluid of glioma does not inhibit the killing action of lymphokine-activated killer (LAK) cells in vitro.

In theory, lymphokine-activated killer (LAK) cells offer a potential method to treat cerebral gliomas, especially low-grade gliomas. LAK cells would be administered by repeated injections straight into the cavity of a subtotally removed tumour. However, brain-tumour cyst fluid has been shown to be immunosuppressive in lymphocyte stimulation tests. Therefore we wanted to know whether the fluid would reduce the killing efficacy of LAK cells. Using a standard cytotoxity test based on 51Cr release, we compared in vitro the cytotoxity of LAK cells against K-562 tumour cells in brain-tumour cyst fluid, autologous serum and allogeneic serum. Five patients with cystic glioma and one with cystic meningioma were studied and no inhibition of cytotoxity of LAK cells was observed.

Kinetics of the metal components of intratracheally instilled stainless steel welding fume suspensions in rats.

The kinetics of iron, chromium, nickel, and cobalt from manual metal arc and metal inert gas stainless steel welding fumes were studied. Neutron activated welding fumes, in aqueous suspensions, were instilled intratracheally into rats. The follow up continued for up to 106 days. From both fumes, approximately 10% of the injection bolus was immediately lost into the gastrointestinal tract, to be recovered in the faeces within three days. Thereafter, a pronounced difference was seen in the kinetics of the two types of fumes. After the first day, chromium, nickel, and iron were lost from the lungs with half times of about 53, 49, and 73 days after exposure to MMA/SS fumes, whereas practically no loss could be seen in the metal components of the metal inert gas welding fumes within two months. The disposition of chromium from MMA/SS fumes closely resembled that of intratracheally instilled water soluble chromates. On the other hand, the disappearance of trivalent chromium from MIS/SS fumes was considerably slower than that of the practically water insoluble chromates, or even of trivalent chromium salts. Thus the physical characteristics of the fume appreciably affect the kinetics of the clearance of chromium compounds from the lungs.

Cytotoxic effects of four types of welding fumes on macrophages in vitro: a comparative study.

The effects of fume particles given off by the manual metal arc (MMA) and metal inert gas (MIG) welding of stainless steel (SS) and mild steel (MS) were studied on rat alveolar macrophage cultures in vitro. The fumes were generated by welding, and particulate material obtained was collected on membrane filters. The macrophage cultures were exposed to the total dust and to its water-insoluble fractions. Cell variability and the release of both lactate dehydrogenase and one lysosomal enzyme from the cells to the medium were measured after an exposure period of 24 h. The cytotoxic control dust was DQ 12 quartz, and the inert control dust was pure titanium dioxide. According to the parameters studied, SS/MMA and MS/MMA welding fumes were cytotoxic to rat alveolar macrophages. The cytotoxic effect of SS/MMA welding fumes decreased after the samples had been washed with phosphate-buffered salt solution. The MIG welding fumes of SS and MS had markedly smaller effects on the cells. Diluted solutions of potassium chromate were also tested in order to investigate its role in the cytotoxicity of SS/MMA welding fumes. The results suggest that hexavalent chromium may be responsible for the cytotoxicity of SS/MMA.

Kinetics of nickel and chromium in rats exposed to different stainless-steel welding fumes.

The kinetics of nickel and chromium from welding fumes were studied in the rat. To study the retention, the duration of exposure was one hour per working day for one, two, three, and four weeks. For the clearance study the follow-up period after four weeks' exposure was 106 days. Multi-element chemical analysis of the fumes and dried lungs was done using instrumental neutron activation analysis, and the concentrations in the body fluids were determined by atomic absorption spectroscopy. The maximum lung retention of metal inert-gas (MIG) welding fumes was somewhat higher than that of manual metal arc (MMA) welding fumes. The estimated maximum concentrations in the lungs were 9.5 micrograms/g and 150 micrograms/g for nickel after four weeks' exposure to MMA and MIG welding fumes. The corresponding concentrations of chromium were 78 micrograms/g and 310 micrograms/g. The measured concentrations were lower, however. The amounts of nickel cleared from the lungs during the MMA and MIG exposures were 0.9 microgram and 8 micrograms. The corresponding amounts of chromium were 9.6 micrograms and 2 micrograms. Practically all of the lost metals were found in the urine, in which the excretion rates were 0.07 microgram/d (MMA) and 0.39 microgram/d (MIG) for nickel and 0.23 microgram/d (MMA) and 0.11 microgram/d (MIG) for chromium.

Retention and clearance of stainless steel shieldgas welding fumes in rat lungs.

The use of metal inert gas (MIG) stainless steel (SS) welding techniques is rapidly increasing. The possible health hazards of MIG/SS welding fumes are not known; more attention has been paid to manual metal arc (MMA) welding. In this study, 52 male Wistar rats were exposed to MIG/SS welding fumes generated by an automatic welding device for "nose only" exposure. For the retention study, the duration of exposure was one hour per workday for 1,2,3, and 4 weeks. For the clearance study, the duration was 4 weeks, and the follow-up period was 106 days. The retention and clearance of the alloyed metals of SS (chromium (Cr), manganese (Mn), nickel (Ni] and iron were studied in the rats' lungs, and the results were compared with the corresponding results of MMA/SS welding. The multielement chemical analysis was made using instrumental neutron activation analysis (INAA); the concentration of exogeneous iron (Feex) was determined by a magnetic measuring method. Feex and Cr were retained in the ratio expected; Mn, Ni and total Fe were retained slower than expected. The total Fe did not clear at all even though Feex cleared with the half-time of 50 d which corresponded well with that of pure magnetite. The accumulation of Cr in the lungs was very high: it cleared with the half-time of 240 d. The clearance patterns of Mn and Ni were very similar. They followed a double exponential model with half-times of 2 d and 125 d for Mn, and 3 d and 85 d for Ni. The results indicated that even though the retention patterns for MMA and MIG welding fumes were very similar, the clearances differed very much.

Stainless steel manual metal arc welding fumes in rats.

Forty two male Wistar rats were exposed to manual metal arc (MMA) stainless steel (SS) welding fumes generated by an automatic welding device for "nose-only" exposure. The exposure simulated an actual MMA/SS welding environment as closely as possible. For the retention study, the duration of exposure was one hour per workday for one, two, three, of four weeks and for the clearance study four weeks. The retention and clearance of the chromium, nickel, and iron found in MMA/SS welding fumes in the rats' lungs were studied as was the distribution of the metals to other organs. Instrumental neutron activation analysis (INAA) was used for the multi-element chemical activation analyses. The concentrations of chromium and nickel in the blood and the urine were determined by atomic absorption method (AAS). The retention of exogenous iron was determined by a magnetic measuring method. The results indicated that the lungs were the target organs of soluble hexavalent chromates. The half times of lung clearance for Cr, Ni, and Fe were 40 +/- 4 d, 20 +/- d, and 50 +/- 10 d. When the lung clearance curves are compared, the half times of Cr and Fe lung clearance are similar but nickel disappears faster. The distribution and clearance patterns of chromium to other organs differ from those obtained after single intravenous or intratracheal injections of alkaline chromates.

Comparison of the behavior of stainless and mild steel manual metal arc welding fumes in rat lung.

The lung retention and clearance of manual metal arc (MMA) stainless steel and mild steel welding fumes were determined in the rat. The exposure simulated the actual welding situation. The duration of exposure in the "nose-only" exposure chamber was 1 h/workday for one, two, three, or four weeks in the retention study and for four weeks in the clearance study. The concentration of exogenous iron was determined by the magnetic measuring method. Instrumental neutron activation analysis was applied to determine the concentration of total iron, chromium, and nickel in the lungs. The results indicated that the lung retention and clearance patterns for the two types of welding fumes were different. A linear relationship was observed between the amount of stainless steel MMA welding fume retained in the lungs and the duration of exposure, whereas the retention of mild steel MMA welding fume in the lung was saturated as a function of the cumulative exposure time rates. The maximum amount of lung-retained contaminants was 880 micrograms for stainless steel MMA welding fume and 220 micrograms for mild steel MMA fume.