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Biomedical subjects

K H Friedrichs

Publications and source records attributed to K H Friedrichs.

At least 19 recordsLinked to original sources

Airborne particulate matter modulates the production of reactive oxygen species in human polymorphonuclear granulocytes.

Causal relationships between airborne particles (especially particulate matter < 10 microm in diameter) and increases in prevalences and symptoms of respiratory diseases have been postulated in many epidemiologic studies. Polymorphonuclear leukocytes (PMN) in the nasal or bronchial epithelium can be exposed to particulate matter (PM) and may upon exposure produce reactive oxygen species (ROS). Release of ROS can result in cellular and tissue damage and initiate or exacerbate inflammation. To elucidate the effect of PM on inflammatory reactions, we exposed human PMN to PM extracts. PM were collected with high volume samplers in two cities, Dusseldorf and Duisburg, in Germany and reflect sites with high traffic and industrial emissions respectively. The collected particles were extracted using water and then dichloromethane, resulting in an aqueous and an organic extract. The production of ROS was determined using luminol-enhanced chemiluminescence (LCL) of resting and zymosan-stimulated PMN. The present study shows that extracts of PM alone significantly stimulated the production and release of ROS in resting PMN. The effects of the PM extracts were inhibited by superoxide dismutase (SOD), catalase and sodium azide (NaN3). Zymosan-induced LCL was, however, diminished by coincubation with PM extracts. The chemical composition is important when considering the effects of particles. Our study shows that only organic substances adsorbed to particles stimulate LCL. SOZ-induced LCL is inhibited by both types of extracts, but aqueous extracts have a stronger inhibitory effect. It is at present unclear which substances are responsible for these effects.

Air Pollutants↗

Asbestos fibers in bronchoalveolar lavage and lung tissue of former asbestos workers.

Bronchoalveolar lavage (BAL) provides a simple method of sampling inhaled particles deposited in the lower respiratory tract. We hypothesized that BAL could be used to measure the quantity and quality of lung asbestos burden. This would be true if BAL fluid asbestos fiber content reflected the total content as well as the size distribution of both uncoated and coated asbestos fibers in lung parenchyma. Therefore, we analyzed the asbestos fiber counts of 23 individual sample pairs in both BAL fluid and lung tissue samples obtained from 20 patients with occupational asbestos exposure using transmission electron microscopy (TEM). In addition, fiber type, fiber size, and aspect ratio were compared. Coated asbestos fibers were found in 10 of 23 BAL samples and 16 of 23 biopsies. The mean concentrations of coated asbestos fibers (i.e., asbestos bodies) in BAL and lung parenchyma showed a positive correlation (r = 0.75, p < 0.001). Likewise, the mean amphibole fiber concentrations correlated positively (r = 0.55, p < 0.01). However, there was no relationship between the mean chrysotile fiber counts in BAL and lung parenchyma (r = 0.18, p = 0.40). Asbestos fibers in lung tissue were significantly longer (8.2 +/- 0.5 versus 4.8 +/- 0.6 microns; p < 0.001) but had the same width (0.12 +/- 0.27 versus 0.11 +/- 0.15 microns; p = 0.24) when compared with those retrieved by BAL from the airspace compartment. The aspect ratio (dividing fiber length by width) was much higher in lung tissue than in BAL fluid (66.4 +/- 0.4 versus 42.9 +/- 0.5; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Asbestos, Amphibole↗

Electron microscopy analysis of mineral fibers in human lung tissue.

In the present study, lung samples from 126 autopsied cases were examined to determine the content of mineral fibers using analytical transmission electron microscopy (ATEM). The cases were divided into four groups (22 lungs of persons exposed to ambient environmental pollution, 32 cases of mesothelioma, 38 cases of primary lung cancer, and 34 asbestosis cases, 13 of these with additional pleural plaques). Fibers were counted, measured, and mineralogically identified using a combination of X-ray microanalysis and electron diffraction of the non-oriented fiber. Concentration of fibrous particles (defined as particles above 1 micron in length with roughly parallel long sides and an aspect ratio of 5:1 and greater) was calculated as fibers 10(6)/g dry lung weight. The concentration of chrysotile was found to be similar throughout the groups except for two cases in the asbestosis group with comparably high numbers of chrysotile. However, a remarkable difference for amphiboles could be observed between the groups. Asbestos bodies were mostly found in the asbestosis group. There was a rather good correlation between numbers of amphibole fibers and asbestos bodies, with an average ratio of 10:1. For comparison purposes between occupationally exposed/non-exposed individuals, a transition was found in the concentration range of 3-10(7) asbestos fibers/g dried lung weight.

Analysis of Variance↗

[Asbestos content in bronchoalveolar lavage fluid].

The concentration and size distribution of bronchoalveolar lavage (BAL) asbestos fibers (AF) longer than 2 microns was determined by analytical transmission electron microscopy (TEM). The concentration of asbestos bodies (AB) was measured by TEM and light microscopy (LM). The study group consisted of 110 patients. 27 patients had no occupational asbestos exposure, 44 patients had occupational exposure to asbestos but no asbestos related disease and 39 patients had asbestos related diseases, either asbestosis (n = 34) or malignant mesothelioma of the pleura (n = 5) following long time asbestos exposure at the working place. Occupational asbestos exposure was reflected by increased asbestos fiber concentration in the BAL samples. Mean fiber concentration and size was different between the groups, but the scatter was large.

Asbestos↗

[Comparative studies of the effect of quartz glass and quartz DQ-12 in inhalation tests in rats].

Fibrogenic effects of amorphous quartz dusts are discussed more and more during recent years. In order to study alterations due to amorphous silica (quartz glass VP 203-006) in comparison with crystalline quartz (DQ-12), an inhalation experiment in rats was carried out. Male Wistar rats were separated in two dust exposed groups (n = 35) and one control group (n = 30). The experiment was carried out in inhalation chambers with a slowly rotating animal cage for 12 months, 7 h per day, and 5 days per week. The dust concentration was 10 mg/m3. After 4 and after 8 months of inhalation, 5 animals of each group were sacrificed. After 12 months 15 rats of the dust exposed groups and 10 controls were euthanized. The remaining animals were kept for another 12 months post-inhalation period. Regarding the macroscopical appearance of the lungs, the relative organ weights and the histomorphological reaction pattern, marked dust depending differences are obvious. In the lungs of DQ-12-exposed animals diffuse structural changes occur, including fibrosis and severe reaction of macrophages. Histology of lungs from quartz glass exposed animals reveals only a slight and focally arranged cellular reaction with a few collagenous fibers. However, in both dust exposed groups the mediastinal lymph nodes are extremely enlarged with severe fibroses. Additionally, the following blood parameters were determined: lysozyme, ACE, GOT, GPT, and AP. The most pronounced changes are detectable in lysozyme and GOT after DQ-12 exposure. After quartz glass exposure, the levels of these parameters are similar to the controls. These results show that the amorphous quartz tested in this experiment (quartz-glass VP 203-006) has to be considered as a compound with certain biological effects. The establishing of occupational standards seems to be justified. But, assessing the effects, the different physical and/or chemical properties of various amorphous quartz dusts have to be considered.

Alanine Transaminase↗

Alveolar and lung fibre levels in non-occupationally exposed subjects.

Mineral fibre concentrations and characteristics were evaluated by the same electron microscope methods in 15 bronchoalveolar lavage samples and in 40 surgical lung tissue samples of subjects with no occupational exposure to asbestos. Both fibre alveolar load and lung burden evaluated by transmission electron microscopy were higher in the groups of industrial workers with no specific asbestos exposure than in the groups of individuals exposed only to general environmental pollution. In both types of samples, the fibre burden consisted of extremely small fibres (mean length less than 2 microns, mean diameter less than 0.1 micron), with a trend towards a further reduction in mean length in the lung tissue as compared with the alveolar load. These data suggest that there is a need for a critical reconsideration of the methods of evaluating environmental fibre pollution and of those for assessing exposure-effect relationships.

Adult↗

Alveolar fiber load in asbestos workers and in subjects with no occupational asbestos exposure: an electron microscopy study.

The alveolar fiber load was evaluated by bronchoalveolar lavage and by scanning and transmission electron microscopy (SEM and TEM) in 50 subjects with or without occupational exposure to asbestos. The concentration of asbestos fibers in bronchoalveolar lavage was significantly higher in the groups of people currently and formerly occupationally exposed, compared to the concentration found in people only exposed environmentally, despite wide interindividual variation within the groups. Nonasbestos inorganic fibers were present in all groups, but the concentrations did not differ significantly. Both in people occupationally exposed and in those only environmentally exposed, the alveolar load consisted mainly of ultrashort and ultrathin fibers, which can be studied only with TEM. In fact, the percentage of fibers greater than 5 micron long was only around 15% in the occupationally exposed and was minimal in those only environmentally exposed. The geometric mean diameters of asbestos fibers retained in the alveoli ranged from 0.05 micron for chrysotile to 0.15 micron for amphiboles.

Asbestos↗

Electron microscopic analyses of dust from the lungs and the lymph nodes of talc-mine employees.

The primary purpose of the present study was to obtain microscopic analyses of the lung and lymph-node dust samples from 12 deceased Austrian workers who had been exposed occupationally to dust of talc and other mineral impurities in a talc deposit for many years. The results of the analyses of both fibers and particles are presented. A second goal of the study was to search for a relationship between different grades of pneumoconiotic effects and the concentration, size distribution and the chemical composition of the retained particles. Automatic analysis of approximately regularly shaped particles with a computer-controlled scanning electron microscope (CCSEM) was used for this purpose, while the fiber content was determined manually on the SEM-screen. The SEM examination of real and irregularly shaped fibers at a magnification of 6000x resulted in an average concentration that was increased slightly in comparison to that found in so-called normal lungs. Fibers were rather short with a mean length of 3 microns; 95% of the fibers had a length less than 10 microns. There was reasonable agreement between medical findings and mineralogical analyses concerning the grade of pneumoconiosis in most of the cases.

Aged↗

Microscopic observations on some fibrous dust samples.

Fibers having a diverse range of physical and chemical properties may be emitted into the atmospheric air mostly as a result of human activities. Because the inhalation by man of certain particles may under some circumstances pose a risk to health, this group of particulate matter has to be measured and identified. Because there is little information about the biological (predominantly carcinogenic) potential as yet, measuring techniques are non uniform as well. In this study, the fiber content of human lungdust specimens has been determined electronmicroscopically for 4 different groups: so called normal lungs (as a control), mesothelioma cases, which may have been spontaneous, or initiated by occupational exposure, fibrosis cases (without any lung tumour) after occupational exposure in coal- and talc-mines. In comparison to the mentioned groups some samples from the atmospheric air in the Ruhr District were analyzed for fibers with the aim of obtaining more information about the shape, length and diameter of this particle group. The data indicated that the size distribution of fibrous particles may be highly different depending upon the previous exposure. Furthermore, elongated particles with irregular shapes may confuse the counting and sizing results (preferentially those of the diameters). Based on the present study, fibrous particles greater than 1 micron in length with a length-to-breadth ratio greater than 10: 1 seem to be of increased biological relevance, if mesothelial risk is the main focus of the investigation.

Air Pollution↗

[A dust generator for inhalation experiments in a high-pressure chamber].

The health effect of inhalable dust particles at working places is predominantly related to "normal" conditions (i.e. temperature = 20 degrees C, atmospheric pressure = 1013 mbar). A probable risk for humans, working in pressurized places (tunnels) raises from modified respiration conditions. An inhalation experiment with rats was performed in a pressurized exposure chamber (1,5 bar). The dust generator was placed in the chamber and consisted of an endless ball-chain, which was lead through a glass-funnel as a dust-store. The average dust concentration ranged between 10 and 14 mg/m3 air. Short-time variations in case of the quartz dust DQ 12 were unavoidable.

Animals↗

[Changes in chrysotile in vivo].

In an animal experimentation rats received a single intratracheal injection of 2 mg chrysotile per animal. Quantitative energy dispersive x-ray microanalysis (EDXA) and selected area electron diffraction (SAED) patterns of the chrysotile fibres, obtained from lung tissue, were performed with the aid of a transmission-electronmicroscope (TEM). During a period of four months the chemical and physical instability of asbestos fibres were investigated. The results of microanalysis were compared with standard chrysotile A, UICC as a reference material. The magnesium-leakage of chrysotile fibres and in the diameter range below 0.1 micrometer was found to be time-depending and increased during the period of the experiment. Opposite to the contents of Ca, the Fe-concentration was not significantly higher. After two months already, a greater number of depleted chrysotile fibres could be analysed. If leakage of magnesium exceeded 80 percentage, the typical single crystal electron diffraction patterns of the chrysotile could not be obtained furthermore. EDXA and SAED are inevitable techniques of identify fibres, which been altered during the period of deposition in animal lungs. There was no evidence to suggest the formation of asbestos bodies during the period of experimentation.

Animals↗

Fibers in human lung dust samples: a scanning electron microscope study.

Since 1977, mesothelioma has been admitted as an occupational disease in the Federal Republic of Germany, if a previous exposure to asbestos at the working place can be proven. In practical work of pathologists the question arises as to how to proceed in the assessment of necropsy cases of mesothelioma, if the patient's occupational history is unknown. In this study, 100 necropsy cases of different exposure were examined by scanning electron microscopy. Concentration and length of fibers were used as criteria to distinguish between spontaneous and occupationally caused cases of mesothelioma. Calculation of the counting results showed that a distinction between the two groups is reliable when fibers greater than 5 micron in length are counted.

Asbestos↗

[Results of animal experiments concerning the carcinogenic effect of fibrous dusts and their interpretation with regard to the carcinogenesis in humans (author's transl)].

After reviewing the hypotheses about the pathogenesis of asbestos-induced malignant tumours we report about experimental data on animals. A high incidence of tumours (most of them mesotheliomas) was induced in rats by intraperitoneal injection of fibrous dusts (chrysotile, palygorscite, crocidolite, glass fibres, nemalite). Treatment with 8 types of granular dusts led though applicating a high dosage (50--100 mg) to neoplasms in only a small percentage of animals. After intraperitoneal application of 2 mg of chrysotile, crocidolite or glass fibres a tumour incidence in a range from 16% to 38% was observed and fibrous reaction was slight. 100 mg of milled chrysotile with relative short fibres (99.8% less than 5 mum, 99.5% less than 3 mum) caused no asbestosis, nevertheless tumours developed in 32% of the rats. Intraperitoneal injection of fibrous dusts also induced mesotheliomas in mice, however not in Syrian hamsters and guinea pigs. Our results point out that the fibrous shape of asbestos dust causes its carcinogenic effect and that furthermore other fibrous dusts can also lead to tumours. Prerequisites are an adequate measure of the fibres and their constancy in the tissue. For these two parameters no exact dates exist. It is estimated that a fibre with a diameter less than 1 mum and a length less than 3 mum exert a cancerogenic effect. Furthermore, a sequence of other factors has an importance for the dose-effect relationship of fibrous dusts. Material of the fibres plays a role in so far it defines the effect producing amount of fibres. The relevance of the results of animal experiments to man is discussed especially with regard to the cancerogenic effect of glass fibres.

Animals↗

[The measurement of fibre concentrations in lung dusts (author's transl)].

Measurements in ambient air have indicated, that air pollution contains fibrous dusts in various concentration. Moreover it seems to be necessary to get informations of the fiber content in the lungs of men. In this investigation 22 dusts, which were isolated by formamide-methode from lungs, were analysed. Methods of preparation and evaluation of the lung dust of people, which were occupational non-asbestos-exposed, are described. Fiber concentration per mg lung dust lies between 10 X 10(3) and 535 X 10(3). Most of the fibers were shorter than 10 mum. Because of the limitation of the evaluation-technique it was not possible to analyse the fibers with regard to their chemical composition.

Adult↗

Tumorigenic effect of fibrous dusts in experimental animals.

Fibrous dusts (chrysotile, glass fibers, nemalite, palygorscite, and gypsum) and granular dusts (actinolite, biotite, hematite, pectolite, sanidine, and talcum) were injected intraperitoneally into rats. The fibrous dusts (other than gypsum) resulted in a high incidence of mesothelioma (30 - 67%). Gypsum produced only 5% and granular dusts none at all. It is suggested that the fibrous shape leads to a high multiplication rate of cells and predisposes to tumor formation. Fibrosis, in the other hand, does not so predispose. Milled chrysotile with 99.8% fibers than 5 mum in length are carcinogenic in our experience. The carcinogenicity of glass fibers in our experiments may have significance for occupational situations.

Abdominal Neoplasms↗