[Conclusions of the special colloquium "Methods of Risk Assessment"].
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Biomedical subjects
Publications and source records attributed to H Valentin.
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We demonstrate here that the CD44 molecule, which mediates lymphocyte adhesion to high endothelial venules (HEV), is also involved in the delivery of an activation signal to the T cell. We have produced a CD44 mAb (H90) which is able to block the binding of lymphocytes to high endothelial venules. H90 had no effect on [3H]TdR incorporation of whole PBL stimulated by lectins, allogeneic cells, or CD3 mAb in the soluble phase; in contrast, it strongly increased [3H]TdR incorporation of PBL stimulated by CD2 pairs of mAb or by CD3 mAb linked to the plastic culture plates, when purified T cells were used, H90 mAb could efficiently induce them to proliferate after a primary signal of activation delivered via cross-linked CD3 or via CD2, an effect mediated by Il-2 synthesis and Il-2R expression. Thus, the effect of H90 mAb resembles the mitogenic effect of CD28 "9.3" mAb. However, several results show that CD28 and CD44 mediate different signals to the T cells: i) in contrast to CD28 mAb, CD44 mAb cannot complement the signal delivered by a soluble CD3 mAb, lectins, or PMA; ii) CD44 mAb, at the difference of CD28 mAb, cannot induce CD3+ thymocytes to proliferate in conjunction with a first signal provided via cross-linked CD3 or via CD2; iii) F(ab) fragments of H90 were efficient, whereas divalent fragments of CD29 9.3 mAb are required to produce activation signals; and iv) CD44 and CD28 mAb produce a very strong synergistic effect on T cell proliferation. These results fit with previous ones showing that endothelial cells can play the role of accessory cell in T cell activation and that a hierarchy of signaling can be delivered to T cells via CD3 and CD2.
Integrins are a superfamily of related molecules whose function, where known, is to mediate adhesion. The so-called very-late-activation antigen (VLA) family includes at least five distinct heterodimers, each composed of a unique alpha-subunit non-covalently associated with a common beta-subunit. Several members of the family have been shown to bind extracellular matrix proteins, but the function of VLA-4 is so far unknown. VLA-4 is the only member of the family detected on thymocytes and resting T cells. We show here that an antibody which recognizes the beta-subunit of VLA-4 (CD29) on T cells can inhibit CD4+ cell proliferation triggered by CD2 or CD3, and that binding of this antibody to activated T cells leads to an increase in cyclic AMP levels which is comparable to that elicited by forskolin. These negative signalling effects are unique to this antibody: other CD29 antibodies do not affect the growth of activated CD4 cells but enhance the proliferation of whole T cell populations and abrogate the suppressive effects of mitomycin-treated CD8 cells on CD4-cell growth. Taken together, our results indicate that VLA-4 functions in cell-cell interactions and that it is the target for the suppressive effects of CD8 cells on CD4 cells.
For the period from 1973 to the end of 1986, 70,656 data sets on occupational preventive medical examinations in employees exposed occupationally to asbestos dust (G 1.2) were made available to us by the Central Registry for Employees Exposed to Asbestos Dust (ZAS). On the basis of this data, an analysis of asbestosis risk was to be made in relation to specific areas of work, taking into consideration the beginning and duration of exposure. Proceedings for declaratory appraisal in accordance with occupational disease no. 4103 were instituted in 1760 cases in the report period. In accordance with the character of the available data, the X-ray findings in the lungs were available from the persons investigated as parameters of possible asbestosis risk on the basis of coding consistent with the International Pneumoconiosis Classification (ILO U/C 1971 and/or ILO 1980 West Germany). The major result of the statistical analyses on the mainframe macrocomputer of the University of Erlangen-Nuremberg was that the relatively highest risk of asbestosis was present in persons whose exposure began before 1955. On the other hand, with increasing duration of exposure, an unequivocal rise of the asbestosis risk could not be detected on the basis of the overall population. In relation to the individual fields of work, the relatively highest risk of asbestosis was shown to be in the asbestos textile and paper industry, as well as in the asbestos cement industry. No detectable risk of asbestosis was present in the fields of mining, traffic and health service and for women in the industrial sectors of building material, gas and water, catering trade, building, commerce as well as banking and insurance. Accordingly, it can be assumed that certain fields of work are or were exposed to such a small extent or not at all that a risk of asbestosis which is relevant in terms of occupational medicine is no longer to be assumed or was not to be assumed. This applies above all to certain work in the frictional coating (brake lining) and asbestos paper industry. Furthermore, the analysis of the data material did not provide any unequivocal indications that inhalative smoking habits have a negative effect on the risk of asbestosis. In principle, it can be stated that the occupational preventive medical investigations according to G 1.2 are effective.(ABSTRACT TRUNCATED AT 400 WORDS)
The results of formaldehyde determinations in the air at various workplaces in the period 1980-1988 are presented. The airborne concentrations varied between less than 0.01 and 10.9 mg m-3 (mean 0.7 mg m-3). For ambient air monitoring, active sampling and capillary gas chromatography are reliable and sensitive methods. Formic acid excretion in urine is an unspecific and insensitive biological indicator for monitoring low-dose formaldehyde exposure.
A cross sectional field study of workers exposed to styrene was performed to evaluate possible acute and chronic neurotoxic effects. A total of 36 workers of four companies handling polyester resin materials for one to 16 years (median: 7 years) and two control groups were each examined on a Monday. The control group 1 (formed to compare acute effects) consisted of 20 men from two companies with no exposure to neurotoxic chemicals. To compare chronic effects, a second control group was formed by "one to one matching" with respect to age, socioeconomic status, and pre-exposure intelligence level. Ambient air monitoring using active sampling (short time) and passive samplers (long time) showed styrene in air concentrations as follows: range 3-251 ppm (median: 18 ppm) and concentrations 140-600 ppm during lamination of the inside of boats. For biological monitoring the results were as follows (postshift samples: range/median): styrene in blood: 5-482 micrograms/dl (39 micrograms/dl), mandelic acid urine: 0.01-3.64 g/l (0.21 g/l), and phenylglyoxylic acid urine: 0.01-0.87 g/l (0.19 g/l). The clinical examination found no signs or symptoms of peripheral neuropathy or encephalopathy. The principal work related health complaints were acute, reversible irritation of the eyes that occurred after exposure to styrene concentrations of 200 ppm or more. The neurobehavioural tests showed no significant differences in acute effects (p greater than 0.05) between the two groups or between preshift and postshift testing. Nor were there any significant differences in the relevant neurobehavioural variables between the styrene workers and the controls. It is concluded that occupational exposure to styrene concentrations in air up to 100 ppm causes no adverse acute or chronic effects on the central nervous system.
The object of the study was to determine whether mercury concentrations in blood and urine were increased directly after placement of non-gamma 2-amalgam fillings. Our cohort consisted of 45 subjects, male and female, age between 19 and 45 years, who had amalgam fillings and were not exposed to mercury on their jobs. Thirty subjects received non-gamma 2-amalgam fillings, 15 did get new fillings. Cold, flameless atom absorption spectrometry was used to analyze mercury levels in blood and urine samples before and for 24 hours after placement of the amalgam fillings at one hour intervals. Mercury concentrations in blood (before and after) and - before placement of new non-gamma 2-amalgam fillings - in urin were below the normal upper limit in all 45 subjects. Mercury concentrations in urin after placement of new fillings did not show any increase over 24 hours. Median values varied between 1.0 and 2.1 micrograms Hg/g creatinine and thus were also within the normal range.
Nickel (Ni) and some of its relatively insoluble compounds as well as chromates may be able to induce cancer in the region of the lungs, as well as in the nose and paranasal sinuses after occupational exposure. Latency periods may amount to 20 years and more. The results of recent investigations have shown that these metals cumulate in the lung tissue after inhalation of relatively insoluble chromium and nickel compounds. The quantitative detection of these heavy metals in samples of pulmonary tissue hence permits the amount of past exposure to be estimated. To establish the normal values, samples of pulmonary tissue from 30 normal subjects were investigated for chromium and nickel content. The samples were taken from different segments and lobes of the lungs, taking topographical anatomical criteria into consideration. In addition, 15 persons who had formerly been exposed to nickel and/or chromium (11 nickel refinery workers, of whom 10 had died of lung cancer, 2 stainless steel welders, 1 foundry worker, 1 electrical technician) were also investigated. From the results of 495 tissue samples from the normal group, median chromium concentrations between 130 and 280 ng/g were calculated, with median nickel concentrations of 20-40 ng/g (wet weight). If these values are related to the nickel concentrations measured in refinery workers, values 112-5,860 times higher were found. The concentrations were about 500 times higher than normal for nickel, and about 60 times higher than normal for chromium in the stainless steel welders. For the foundry workers who died of lung cancer, chromium and nickel concentrations in the normal range were calculated, with the exception of the nickel concentrations in the upper and lower lobes of the right lung. The very high nickel concentrations found in the samples of lung tissue from former nickel refinery workers should be regarded as a guideline with regard to the appraisal of the causal relationship between lung cancer and occupational exposure to relatively insoluble nickel compounds. This result is also supported by epidemiological investigations on this subgroup and must thus be considered etiologically conclusive. For the welders, chromium and nickel concentrations were found that were markedly above normal, but as yet there is no epidemiologically reliable verification for the increased occurrence of malignancies in this occupational group.(ABSTRACT TRUNCATED AT 400 WORDS)
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In 15 random autopsies, nickel (Ni) and chromium (Cr) were determined quantitatively by atomic absorption spectrometry (AAS) in human lung tissue to evaluate norm values. None of the deceased persons had had an occupational exposure to Cr or Ni or their compounds. In all, 22 tissue samples were taken from each lung at specific topographical anatomical locations. The analytical procedure is described in detail. The results showed substantial variation in concentrations both within a single lung and also between individuals. Median values found were 204 ng/g for Cr and 25.6 ng/g for Ni. Topographical concentrations of Cr and Ni were 1.3-1.9 times higher in the upper lung areas. In view of the variability in metal concentration, analysis of only one part of lung tissue is not sufficient for determining the content of the entire lung. The evaluation of norm values is an important precondition for appraisal of Cr and Ni accumulation in human pulmonary tissue that may be due to occupational exposure.
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Prevention is of increasing importance in medicine, particularly in occupational medicine. The programs of health surveillance at the workplace in the Federal Republic of Germany are discussed. In 1983, 1,400,000 examinations of employees were performed; exclusion criteria were fulfilled in 2.1% (0.9% only temporarily). In 1984 the respective numbers were 1,450,000 examinations (1.8%, 0.8%). During the last few years, health surveillance programs markedly have improved the efficiency of prevention of occupational diseases. They will be an important task for occupational physicians in the future.
Analyses of Cadmium (Cd) in human specimens demand special interest since the Federal Environmental Agency of West-Germany (UBA, FRG) has published calculations and high figures of renal disturbances due to Cd. We analyzed autopsy material from the Cd-polluted area of Goslar/Harz Mountains (N = 28) and from the less contaminated region Erlangen/Nürnberg (Franconia) (N = 50). As determinants of Cd-concentration special regard was given to age, smoking habits, residence (urban/rural), and medical findings (nephropathy, hypertension). A balanced distribution of age is found in all subdivisions, the mean age of death is 66 and 68 yrs., respectively, in both regions. Median values of Cd-concentrations in the target organs from Franconia were found to be half the amount of those from Goslar (renal cortex: 12/19, medulla: 8/16, liver: 1/3 micrograms Cd/g wet weight). Significant local differences are found for renal medulla and liver (p less than 0.05). In both regions the Cd-content is independent from sex and residence (urban/rural). The influence of tobacco smoking on the Cd-burden is evident (greater than 50%). Cases of hypertension show maximum values, although this trend can't be confirmed by the median values. Regional Cd-pollution seems to have more effect than pathological findings: normotensive persons from Goslar have higher median renal Cd-concentrations than hypertensive patients from Franconia. Analyses of renal diseases reveal the same result. All Cd-concentrations are far below the critical value (200 micrograms Cd/g renal cortex, w.w.). The evaluation of such limit values and the results of similar studies are briefly discussed.
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The aim of this longitudinal study was to investigate whether long-term exposure to styrene is associated with functional disorders of the peripheral nervous system. Eleven workers (age: 24 to 54 years) of a polyester resin boat industry were studied neurophysiologically and biochemically in 1980 and 1983. The duration of styrene-exposure varied from 3 to 7 years, with a median of 4 years. The control group was comprised of 11 non-styrene-exposed workers of similar age. Air Monitoring with passive samplers was performed on different days for each person. The mean styrene concentrations were 114, 97 and 92 ppm respectively and therefore in the magnitude of the current MAK-value of 100 ppm in the Federal Republic of Germany (FRG). For Biological Monitoring styrene in blood (S-B) and mandelic acid (MA) as well as phenylglyoxylic-acid (PGA) in urine were determined in post-shift samples. The median values for MA at four different sampling times were 816, 1660, 1101 and 1224 mg/g creatinine and for PGA 200, 273, 342 and 336 mg/g creatinine respectively. These levels were below the current "Biologischer Arbeitsstoff Toleranzwert (BAT-Wert)" for MA (2000 mg/l) and MA + PGA (2500 mg/l). The S-B concentrations ranged from 0.05 mg/l to 3.26 mg/l, with mean values of 0.92 and 0.70 mg/l. The nerve conduction velocities (NCV) of motor and sensory nerve fibers (N. ulnaris and/or N. medianus) showed no significant differences between styrene-exposed workers and age-matched control persons. There were no hints of "dose-effect-relationships" by correlation analyses. Furthermore the follow-up determination revealed no significant changes regarding NCV.(ABSTRACT TRUNCATED AT 250 WORDS)
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