PubMed Health⌕ Search

Biomedical subjects

F Pott

Publications and source records attributed to F Pott.

At least 37 records · Page 2Linked to original sources
PubMed1997

Fiber-specific molecular features of tumors induced in rat peritoneum.

Molecular markers such as mutational spectra or mRNA expression patterns may give some indication of the mechanisms of carcinogenesis induced by fibers and other carcinogens. In our study, tumors were induced by application of crocidolite asbestos or benzo[a]pyrene (B[a]P) to rat peritoneum. DNA and RNA of these tumors were subjected to analysis of point mutations and to investigation of mRNA expression patterns. With both assays we found typical features depending on the type of carcinogen applied. The analysis of point mutations in the tumor suppressor gene p53 revealed mutations in the B[a]P-induced tumors. However, in the tumors induced by crocidolite asbestos that were of the same tumor type as those induced by B[a]P, mutations in p53 were not detectable. Every mutation detected on the DNA level causes an amino acid substitution within one of the functional domains of the tumor suppressor protein. Therefore, these mutations seem to be of biological relevance for tumor progression and indicate a difference in the carcinogenesis regarding the type of the carcinogenic substance. An additional specificity of crocidolite-induced tumors was detectable by analyzing the mRNA expression of the tumor suppressor gene WT1, which is known to be expressed in human mesothelial and mesothelioma cells. A relatively high amount of WT1 mRNA was measured by quantitative competitive reverse transcription-polymerase using RNA extracted from crocidolite-induced tumors. However, WT1 seems to be expressed on a rather low level in tumors induced by B[a]P.

Abdominal Neoplasms↗
PubMed1997

Dose-response relationship of fibrous dusts in intraperitoneal studies.

The relationship between the number of fibers injected intraperitoneally and the occurrence of peritoneal mesotheliomas in rats was investigated using data from a series of carcinogenicity studies with several fibrous dusts. Based on observed tumor incidences ranging between 10 and 90%, the hypothesis of a common slope of dose-response relationships (parallel probit lines in probit analysis) cannot be rejected. In general, parallelism of probit lines is considered an indication of a common mode of action. Analysis of the shape of the dose-response relationship, with one apparent exception, shows virtually linear or superlinear behavior, i.e., from these data, there is no indication of a decrease in carcinogenic potency of an elementary carcinogenic unit at lower doses.

Animals↗
PubMed1997

[Current data and questions on the carcinogenicity of solid particles of diesel engine exhaust and other sources].

During the last few years, the findings could be confirmed which led to the conclusion that very fine solid particles which are not known to have an intrinsic toxicity, can induce lung tumours in rats. The carcinogenic potency seems to increase parallel to increasing specific surface area and decreasing particle size. However, many questions remain open. Organic compounds which contain many carcinogenic polycyclic aromatic hydrocarbons (PAH) can explain only less than 1% of the carcinogenic effect of diesel exhaust in the rat lung. Therefore, the carcinogenicity of diesel exhaust cannot be reduced by an oxidizing catalyst. It burns a part of the organic substances adsorbed on the surface of the carbonaceous core of diesel particles and thus helps to follow the low standard for particles in diesel emissions, but without reduction of the carcinogenic potential because it does not reduce the emission of the insoluble carcinogenic part of the particles, the elementary carbonaceous core. The search for a hypothetical threshold for the carcinogenicity of particles in the rat lung aims at the determination of mechanisms which are preconditions for the development of a tumour. If certain doses do not induce such lesions they are considered safe. Chronic inflammation, proliferation of epithelial cells and fibrosis are discussed to be preconditions. However, the pathways which lead to inflammation and proliferation could proceed independent of the molecular carcinogenesis. Therefore, a cancer risk from diesel particles and other very fine particles may occur under environmental conditions. If the positive epidemiologic studies are relevant, a lung cancer risk for humans can be calculated which is higher than that calculated from inhalation studies with rats.

Administration, Inhalation↗
PubMed1996

Dissociated cerebral vasoparalysis in acute liver failure. A hypothesis of gradual cerebral hyperaemia.

BACKGROUND/AIMS: Normally, cerebral blood flow responds to changes in the arterial carbon dioxide tension (PaCO2) but not to changes in mean arterial pressure, commonly referred to as the cerebral CO2-reactivity and autoregulation. In patients with fulminant hepatic failure and in the rat with thioacetamide-induced liver failure, autoregulation is absent, presumably due to cerebral vasoparalysis. Since also CO2-reactivity may then be compromised, it was studied in patients with fulminant hepatic failure and rats with thioacetamide-induced liver failure. METHODS: In ten patients (median age 32 (range 20-48) years)) and in ten age-matched volunteers, cerebral perfusion was elevated by transcranial Doppler assessed mean flow velocity (V(mean)) in the middle cerebral artery during hypo- and hyper-capnia. In six rats with liver failure and in six control rats, cerebral blood flow was measured repeatedly by the intracarotid 133 Xenon injection technique. RESULTS: In the patients and volunteers, PaCO2 was lowered from 33 (23-44) to 28 (23-39) mmHg by hypocapnia and raised to 40 (34-48) mmHg by hypercapnia or 5% CO2 inhalation. During hypocapnia, the CO2-reactivity did not differ significantly between patients and volunteers, 4.0 (1.1-7.4) vs. 3.0 (1.7-5.0)% mmHg(-1), while it was reduced during hypercapnia in the patients, 2.2 (1.8-5.2) vs. 4.6 (3.0-8.0)% mmHg(-1) (p < 0.05). In the rats, PaCO2 was reduced from 39 (37-40) to 30 (29-31) mmHg and then raised to 51 (41-55) mmHg. During hypocapnia, CO2-reactivity was similar in rats with liver failure and in control rats, 2.3 vs 2.7% mmhg(21), respectively. In all rats with liver failure CO2-reactivity was abolished during hypercapnia, while it was 1.5% mmHg(-1) in the control rats (p < 0.01). CONCLUSIONS: The finding that cerebral CO2 reactivity is reduced in hypercapnia, while it is preserved in hypocapnia, suggests that gradual dilation of the cerebral resistance vessels develops in fulminant hepatic failure and connects previous morphological studies with changes in the regulation of cerebral blood flow, i.e. impaired cerebral autoregulation and blunted CO2-reactivity.

Acute Disease↗
PubMed1996

Results of current intraperitoneal carcinogenicity studies with mineral and vitreous fibres.

The study includes some 50 groups of male or female Wistar rats tested in three series. Except for one untreated group and 3 vehicle control groups, the animals were injected intraperitoneally (i.p.) once or repeatedly with dust suspensions and then examined, after lifetime observation up to 30 months, for tumours in the abdominal cavity. 1 granular dust (silicon carbide), 2 asbestos dusts (crocidolite, tremolite) and 11 vitreous fibre dust samples were administered. 5 of the vitreous fibre types were fine fibre fractions from 4 commercial insulation wools and 1 experimental wool, the others were prepared by milling glass microfibres, which have, per se, a small diameter range. The dosage per rat differed over a wide range in accordance with experience from earlier studies. The lowest dose was 0.04 x 10(9) crocidolite fibres in 0.5 mg dust, and the highest amounted to 20 x 10(9) glass fibres in 1000 mg divided into 40 weekly injections. Two mesotheliomas were found in a total of 395 rats treated with saline or granular silicon carbide (250 or 1000 mg). Eleven fibre dusts produced dose-dependent mesotheliomas at rates of up to 97 %, but the calculated fibre number > 5 micrometers in length required for inducing a 25 % tumour risk differed between the fibre samples tested in the relation of 1 to about 1000. UICC-like crocidolite heads the ranking order; the glass fibre B-01, which possesses a low durability in the body, ends it together with a rather thin sample of glass fibre type B-09. The stone fibre MMVF-21 takes a high place in the ranking order, similar to the tremolite sample. The results correspond to those of earlier i.p. tests.

Abdominal Neoplasms↗
PubMed1996

Central command increases cardiac output during static exercise in humans.

Neural control of the circulation during static two-leg exercise was evaluated in 10 subjects. External compression of the legs was employed to assess muscle mechano-receptor influence by achieving the same intramuscular pressure (80 mmHg) as developed during exercise. The muscle metabo-reflex contribution was assessed by post-exercise muscle ischaemia, and the influence from higher centres in the central nervous system ('central command') was taken as the part of the response that could not be accounted for by the two reflex contributions. During static exercise, mean arterial pressure was higher (26 +/- 3 mmHg; P < 0.01) as compared with leg compression (10 +/- 2 mmHg) and with post-exercise muscle ischaemia (11 +/- 2 mmHg). Heart rate (25 +/- 4 b.p.m.) and cardiac output (0.8 +/- 0.3 L min-1) were increased only during static exercise (P < 0.05). Increase in total peripheral resistance were similar during static exercise, post-exercise muscle ischaemia and leg compression. The pressor response to static exercise with a large muscle group was equally attributable to mechanical and metabolic stimulation of afferent nerves; and the two influences were redundant in their effect on total peripheral resistance. In contrast, the influence from central command was directed to the heart with elevation of its rate and minute volume.

Adult↗
PubMed1996

Middle cerebral artery blood velocity and plasma catecholamines during exercise.

During dynamic exercise, mean blood velocity (Vmean) in the middle cerebral artery (MCA) demonstrates a graded increase to work rate and reflects regional cerebral blood flow. At a high work rate, however, vasoactive levels of plasma catecholamines could mediate vasoconstriction of the MCA and thereby elevate Vmean at a given volume flow. To evaluate transcranial Doppler-determined Vmean at high plasma catecholamine levels, seven elite cyclists performed a maximal performance test on a bicycle ergometer. Results were compared with those elicited during five incremental exercise bouts and during rhythmic handgrip when plasma catecholamines are low. During rhythmic handgrip the Vmean was elevated by 21 +/- 3% (mean +/- SE), which was not statistically different from that established during moderate cycling. However, at the highest submaximal and maximal work intensities on the bicycle ergometer. Vmean increased by 31 +/- 3% and 48 +/- 4%, respectively, and this was significantly higher compared to handgrip (P < 0.05). During maximal cycling, plasma adrenaline increased from 0.21 +/- 0.04 nmol L-1 at rest to 4.18 +/- 1.46 nmol L-1, and noradrenaline increased from 0.79 +/- 0.08 to 12.70 +/- 1.79 nmol L-1. These levels were 12- to 16-fold higher than those during rhythmic handgrip (adrenaline: 0.34 +/- 0.03 nmol L-1; noradrenaline: 0.78 +/- 0.05 nmol L-1). The increase in Vmean during intense ergometer cycling conforms to some middle cerebral artery constriction elicited by plasma catecholamines. Such an influence is unlikely during rhythmic handgrip compared with low intensity cycling.

Adult↗
PubMed1995

Detection of mineral fibre carcinogenicity with the intraperitoneal test--recent results and their validity.

The general experimental design of intraperitoneal (i.p.) carcinogenicity studies with inorganic fibres in rats is described. In a current study, in addition to glass microfibres, size-separated fine respirable fractions of commercial insulation wools (MMVF-11 and MMVF-21) also induced mesotheliomas after i.p. injection of 0.4 x 10(9) fibres. These fibre samples were also tested in inhalation studies. A special glass fibre type (B-01), which is of interest because of its low biodurability, induced tumours with 25- and 50-fold higher doses. The i.p. model has been proved to be much more specific and sensitive for testing the carcinogenicity of inorganic fibres than the inhalation model. Objections to this conclusion are cited and discussed with alternative arguments.

Animals↗
PubMed1995

Cerebral perfusion during human liver transplantation.

During transplantation of the liver cerebral perfusion was monitored by transcranial Doppler determined middle cerebral artery mean flow velocity (Vmean) and pulsatility index (PI) in six fulminant hepatic failure patients and 11 patients with chronic liver disease. In both groups of patients Vmean, PI and central haemodynamic variables were recorded during (1) the last preanhepatic hour; (2) the anhepatic phase; (3) the first 15 min of reperfusion; and (4) for the following 45 min of reperfusion. No significant differences were detected between the two groups of patients with respect to changes of variables with time. The Vmean (40 +/- 13 cm s-1 [mean +/- SD]), thoracic electrical impedance (TI) (30 +/- 7 Ohm), heart rate (97 +/- 19 beats min-1), mean arterial pressure (84 +/- 9 mmHg) and arterial carbon dioxide tension (PaCO2, 4.5 +/- 0.4 kPa) remained stable in the anhepatic phase, while cardiac output (CO, 7.6 +/- 2.7 to 5.4 +/- 1.41 min-1), stroke volume (SV, 79 +/- 26 to 56 +/- 15 ml) and PI (1.2 +/- 0.3 to 0.9 +/- 0.2) decreased (P < 0.05). During reperfusion, CO (9.9 +/- 4.01 min-1), SV (105 +/- 40 ml), PaCO2 (5.5 +/- 0.6 kPa), Vmean (57 +/- 17 cm s-1) and PI (1.2 +/- 0.2) became elevated. Taken together, during the anhepatic phase of the liver transplantation a maintained central blood volume as indicated by the constant TI served for a stable blood pressure and in turn cerebral perfusion, whereas revascularization of the graft increased cerebral perfusion concomitant with an elevated carbon dioxide tension.

Adult↗
PubMed1994

Pulmonary alveolar proteinosis in rats after administration of quartz: its possible role in morphogenesis of lung cancer.

In rats, primary peripheral lung tumors composed predominantly of alveolar type II cells have been induced by inhalation of alpha quartz. In our retrospective study on proliferation markers we evaluated lung specimens of 140 Wistar rats from larger experiments, which had been exposed to Dörentrup quartz (DQ12) by inhalation (10 mg/m3, 56 Weeks, 5 days/week, 7 h/day: n = 27) or intratracheal instillations (5 mg: n = 38; 20 mg: n = 10; 50 mg: n = 28; 15 x 3 mg: n = 12). In the last group 8/12 animals developed lung tumors. Animals were sacrificed 1-32 months after administration. For identification of an increased proliferation of alveolar type II cells the DNA content was monitored by microscopic (static) cytophotometry in histological slides. The argyrophil (AgNOR) method for the demonstration of nucleolar organizer regions (NOR) was used as second marker of type II cell proliferation. Measurements made 24 months after inhalation of DQ12 showed a slight increase of pneumocytic proliferation with 1.64 +/- 0.14 AgNOR/nucleus compared to the controls (1.23 +/- 0.04 mean AgNOR/nucleus). After intratracheal instillation of DQ12 a significant increase of AgNOR was found, e.g. 5 mg: 1.93 +/- 0.23 AgNOR/nucleus (6 months) and 1.96 +/- 0.19 (12 months); 50 mg: 1.77 +/- 15 (6 months) and 2.18 +/- 0.05 (12 months); 15 x 3 mg (+2 ml 2% polyvinylpyridine N-oxide s.c.): 1.81 +/- 0.13 AgNOR/nucleus (27-32 months). With the aid of the 2 c deviation index, i.e. the mean square deviation from the diploid DNA value, it was possible also to identify the pathologically increased proliferation of type II cells after intratracheal instillation of quartz: 0.02 +/- 0.01-0.06 +/- 0.04 c2 (controls); 0.07 +/- 0.04 c2 (5 mg/12 months); 0.12 +/- 0.08 c2 (15 x 3 mg/>27 months) and 0.68 +/- 0.48 c2 (50 mg/12 months). Only in the last group were nearly triploid values detected. Summarizing our results, intratracheal instillation and inhalation of quartz in rats regularly induces alveolar proteinosis and interstitial fibrosis in combination with a dose- and time-dependent increase of the type II cell proliferation rate. As mitogenesis increases carcinogenesis, alveolar proteinosis with increased pneumocytic proliferative activity might be a prerequisite for enhanced tumor development.

Animals↗
PubMed1994

Estimation of a lifetime unit lung cancer risk for benzo(a)pyrene based on tumour rates in rats exposed to coal tar/pitch condensation aerosol.

Female Wistar rats were exposed to coal tar/pitch condensation (CTP) aerosol containing either 20 or 46 micrograms/m3 benzo(a)pyrene (BaP) among other polycyclic aromatic hydrocarbons (PAH) 17 h/day and 5 days/week for 10 or 20 months followed by a clean air period of up to 20 or 10 months, respectively. Based on the inhaled BaP, given as BaP exposure concentration multiplied by the total exposure time, the cumulative dose of inhaled BaP of the 4 exposure groups was 71, 142, 158 and 321 mg BaP/m3 x h and the corresponding lung tumour rates were 4.2, 33.3, 38.9 and 97.2%. There was no lung tumour in the control group. Using the US Environmental Protection Agency (EPA) linearized multistage model, the lifetime lung tumour risk for rats exposed to 1 microgram/m3 BaP as a constituent of a complex PAH mixture may be 2% or correspondingly 2 per 100,000 with a BaP concentration of 1 ng/m3. The estimation of the unit lung cancer risk for BaP based on epidemiological data from coking plants was 7-9%.

Administration, Inhalation↗
PubMed1994

Asbestos use and carcinogenicity in Germany and a comparison with animal studies.

The centralized structure of economic affairs in the former German Democratic Republic (East Germany) and the isolation from the free market led to the situation that imported asbestos was almost exclusively chrysotile. More than 90% came from the Kiembay mining area in the Ural Mountains, and about 7% was long-fibre chrysotile from Canada. Sturm and co-workers detected 1082 mesothelioma cases from 1960 to 1990 in the counties of Magdeburg and Halle. In 843 of these cases an exposure to asbestos was evident. Seventy-two cases were exposed to chrysotile only. Suspected exposure to amphiboles imported before World War II or to fibre contained in talc could not be substantiated. Up to now, there have been no analyses of lung fibre burdens from such cases. Reviewing the carcinogenicity studies in rats performed by inhalation or intra-cavitary injection of chrysotile, amosite and crocidolite fibres, the results give no clear indication of a lower carcinogenic potency per chrysotile fibre than per amphibole fibre if equal fibre numbers and fibre sizes are applied, although the chrysotile content of the lungs is relatively low. Also the mesothelioma rates after inhalation exposure to extremely high concentrations of the different asbestos fibre types are similar for chrysotile and the amphiboles and in the region of 5%. Compared with the asbestos-related cancer rates in chrysotile textile workers, rats have to be exposed to a more than 100-fold higher fibre concentration than humans to induce the same lung tumour incidence.

Animals↗
PubMed1994

Significance of durability of mineral fibers for their toxicity and carcinogenic potency in the abdominal cavity of rats in comparison with the low sensitivity of inhalation studies.

At the same time that carcinogenicity of very thin glass fibers after intrapleural and intraperitoneal (ip) administration was demonstrated (1,2) researchers found that gypsum fibers and HCI-leached chrysotile fibers were easily soluble in the peritoneal cavity. This led to the conclusion that the chemical composition of fibers was not responsible for the carcinogenesis but that the degree of carcinogenic potency of a fiber depended on the extent to which it retained its fibrous structure. A thin glass fiber with a low biodurability did not induce tumors after ip injection of a high dose, although the ip test had been criticized for being "overly sensitive." The ip model has been the most successful for determining carcinogenicity of inorganic fibers and establishing dose-response relationships; but to determine the possibilities and limitations of this test model, very high doses of nonfibrous silicon carbide and of a slightly durable glass fiber type were injected ip in Wistar rats. No obviously acute or chronic toxic effect was observed in 90 weeks, but there was a 40% incidence of serosal tumors in the group treated with glass fibers. A pilot study on the persistence of slag fibers in the omentum of rats after ip injection showed a half-time of about 1 year. It was calculated that an ip injection of 10(9) fibers would lead to a concentration of fiber numbers in the ash of the omentum in the same range as the concentration in the lung after 2 years of inhalation exposure. The long-term inhalation study with fibers in rats has been called the "gold standard" for risk characterization.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗
PubMed1994

Comparative investigations of the biodurability of mineral fibers in the rat lung.

The biodurability of various glass fibers, rockwool, and ceramic fibers was examined in rat lungs and compared with natural mineral fibers. Experiments were based on studies that have shown that the biodurability of fibers is one of the essential factors of the carcinogenic potency of these materials. Sized fractions of fibers were instilled intratracheally into Wistar rats. The evenness of distribution of fibers in the lung was checked by scanning electron microscopy (SEM) or careful examination of the fiber suspension before treatment. After serial sacrifices up to 24 months after treatment, the fibers were analyzed by SEM following low temperature ashing of the lungs. Parameters measured included number of fibers, diameter, and length distribution at the various sacrifice dates, so that analyses could be made of the elimination kinetics of fibers from the lung in relation to fiber length (FL). Size selective plots of the fiber elimination correlated with fiber diameters enables the mechanism of the fiber elimination (dissolution, fiber breakage, physical clearance) to be interpreted. The half-time of fiber elimination from the lung ranges from about 10 days for wollastonite to more than 300 days for crocidolite. The biodurability of man-made vitreous fibers (MMVF) is between these values and is dependent on the chemical composition of the fibers and the diameter and length distribution. Results indicate that the in vivo durability of glass fibers is considerably longer than expected from extrapolation of published data on their in vitro dissolution rates.

Animals↗