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Biomedical subjects

R E Edwards

Publications and source records attributed to R E Edwards.

52 records · Page 3Linked to original sources

Early changes in the pleural mesothelium following intrapleural inoculation of the mineral fibre erionite and the subsequent development of mesotheliomas.

Changes in the pleura of rat lungs after intrapleural inoculation of the fibrous zeolite, erionite, have been examined from the earliest stages of reaction through to the eventual development of mesotheliomas. The initial changes involve haemorrhaging and pleural inflammation and proliferation with localized destruction of the elastic membrane under the visceral pleura. This allows cell proliferation into the lung parenchyma with fibres being able to penetrate into the lung. The chronic stimulation of the pleura by erionite eventually leads to the development of mesotheliomas which are invasive or compressing. The tumours are derived from the epithelial cells of the mesothelium (as shown by cytokeratin staining) or the subserosal cells beneath the mesothelium. Both types of mesothelioma can be invasive and some show an unusual property of 'tracking' along the blood vessels in the parenchyma as they invade. In dose-response terms for mesothelioma formation, erionite is over 200 times more tumourogenic than crocidolite (blue) asbestos.

Aluminum Silicates↗

Dyspnea in aging rats due to disseminated intravascular coagulation (DIC).

During an 18-month oncogenicity study using rats, approximately 10% of the animals developed a form of respiratory distress very similar to that seen in the terminal stages of chronic respiratory disease, commonly associated with Mycoplasma pulmonis infection. Investigation of the lungs of the affected rats revealed not only that they did not have the consolidation usually associated with chronic respiratory disease, but they also appeared macroscopically normal. Further investigation of a number of cases revealed systemic intravascular thrombus formation of the type usually referred to as disseminated intravascular coagulation. Using an antiserum to fibrin we have demonstrated the presence of intravascular fibrin deposits in the lungs of the affected rats and have shown them to be the same as experimentally induced intravascular fibrin deposits induced in rat lungs by the administration of thrombin after blocking the fibrinolytic system. This is the first example of such a phenomenon being recorded in aging rats.

Aging↗

Cytokeratin expression in cells of the rodent bile duct developing under normal and pathological conditions.

A polyclonal anti-cytokeratin antibody has been used to examine the expression of this intermediate filament both during normal development in the rat and in a variety of pathological states in the rat and mouse. Bile duct proliferation induced by the administration of alpha-naphthylisothiocyanate (ANIT) as well as the oval cell proliferation induced by 3'-methyl-4-dimethylaminoazobenzene (3-MeDAB) have been used to examine the expression of the rodent cytokeratins in the proliferating cells regarded as being of bile duct origin. Examples of cholangiofibrosis and cholangiocarcinomas were also examined for evidence of cytokeratin expression using this antibody, as well as proliferations of a morphological intermediate type between epithelial and mesenchymal. In all cases we have been able to demonstrate continuity of phenotypic expression of the cytokeratins recognized by this antibody in cells which are recognized as bile duct in origin, even where their morphological appearance does not resemble an epithelial cell type. Because this antibody can be used on formalin-fixed, paraffin-processed tissues, after trypsin treatment, it is proposed that it can be used routinely in the toxicological evaluation (even retrospectively) of bile duct related proliferations and tumours.

1-Naphthylisothiocyanate↗

The use of vimentin antibodies in the diagnosis of malignant mesothelioma.

An immunohistochemical investigation of vimentin, an intermediate filament, was carried out on formalin fixed paraffin embedded sections of 44 malignant mesotheliomas of the pleura and 24 pulmonary adenocarcinomas, in order to assess its value in differential diagnosis. Seventy-five percent of the malignant mesotheliomas showed positive staining for vimentin. An unexpected finding was the presence of vimentin in 46% of the pulmonary adenocarcinomas. In either case there was no correlation between the presence of vimentin and the histological types or grades of differentiation. The overall level of vimentin staining was significantly greater in the malignant mesotheliomas than in the pulmonary adenocarcinomas but no single antibody dilution was found to provide clear cut separation of the two groups. Vimentin does not appear to be a simple discriminatory marker of malignant mesothelioma.

Adenocarcinoma↗

Cell population and histochemistry of asbestos related lesions of rat pleural cavity after injection of various inorganic dusts.

Rats injected intrapleurally with either crocidolite or chrysotile asbestos or silica or saline, were killed at intervals up to 2 years of age. The pleural cavities were washed out immediately after death and the washing used for enumerating cells. In addition tissue from granulomas and mesotheliomas was sectioned and stained for lysosomal enzymes. The total cellular response to silica found in the washout showed a pronounced increase when compared with either asbestos dust or controls; crocidolite gave a decreased response in an early group of the individual cells studied. The most important finding was a decrease in the number of mast cells found to be associated with the injection of both types of fibres. Crocidolite induced granulomas showed the presence of lysosomal enzymes and non-specific esterase in mononuclear cells and giant cells, even two years after injection. With chrysotile, giant cells were only present up to three to four months, and few positively staining cells were noted after 18 months. While the response of cells in the pleural cavity does not differ greatly between the two types of fibres, that in the granulomas highlights the longer lasting action of crocidolite.

Animals↗

Mast cells and inhalation of asbestos in rats.

Mast cell counts were performed on sections taken from the lungs of rats exposed by inhalation to different UICC samples of asbestos fibres for periods ranging from a few days to two years. A comparison of mast cell counts with grades of fibrosis showed that there is a sevenfold increase when there is interlobular linking of the fibrotic lesions (grade 5). Submesothelial mast cells showed a trend of increasing numbers with increasing exposure and with increasing subpleural thickening. Each type of asbestos produced a steady increase in mast cell numbers with increasing exposure. Two samples from animals exposed to chrysotile and two from animals exposed to amphiboles (crocidolite and amosite respectively) had 10 times as many cells as the control group after six and 24 months' exposure. Another amphibole, anthophyllite, produced 50 times more cells than were present in the control specimen appropriate for the heaviest exposure. These results are briefly discussed in relation to further exposure, smoking, and characteristics of the dusts.

Animals↗

Pluripotential nature of mesotheliomata induced by inhalation of erionite in rats.

Mesotheliomata can be induced more rapidly and more frequently by inhalation of erionite than by asbestos inhalation. Erionite-induced tumours have in general a similar ultrastructural appearance to inoculum-induced pleural and peritoneal mesotheliomata. Unusual features of these tumours were the presence of dense-cored vesicles and cells staining positively for neuron-specific enolase which indicated the presence of endocrine cells. In addition, one tumour showed differentiation towards bone-forming cells. The expression of both epithelial and mesodermal characteristics demonstrates the pluripotential nature of mesothelial cells under certain circumstances.

Aluminum Silicates↗

Effects of chrysotile asbestos on mononuclear cells in vitro.

Chrysotile asbestos (400 micrograms/ml) was not found to be cytotoxic towards human blood lymphocytes in culture over a 72 h period, although there was indirect evidence of cytoxicity towards plastic adherent mononuclear cells (PAM). There was significant suppression of 3H-thymidine incorporation into cells cultured with phytohaemagglutinin (PHA) in the presence of fibres. It was found even when chrysotile was added 24 h after PHA. No suppression was found for chrysotile-treated PAM-depleted cultures in comparison to control cultures. Antibody-dependent cell-mediated cytotoxicty (ADCC) was inhibited by the presence of chrysotile, and appeared to be due to prevention of contact between antibody-coated target cells and effector cells.

Antibody-Dependent Cell Cytotoxicity↗

Sequential immunological studies on an asbestos-exposed population. I. Factors affecting peripheral blood leucocytes and T lymphocytes.

Peripheral blood leucocyte counts, and E binding rosettes were measured on 138 men on five separate occasions. Little effect was seen from age, or length of asbestos exposure. Overall the most marked effect was that obtained from smoking. Most relevant was an increase in percentage of E-rosettes read after 1 1/2 hrs, which was obtained in the group of those with radiological evidence of fibrosis who smoked. Restricted to subjects with small opacities, those who smoke have a significantly higher (P less than 0.05) percentage E 1 1/2 hr rosettes than those who do not smoke. (Percentage E rosettes read overnight remained unaltered by smoking or X-ray). This increase was found on each occasion that it was measured. Since the absolute number of T lymphocytes rosetting at 1 1/2 hr did not increase, it is suggested that there is either no stimulation of the central pool of T lymphocytes or a decrease in the absolute number of T lymphocytes which could only rosette overnight.

Adult↗

Lacunarity for compact groups.

Let G be a compact Abelian group with character group X. A subset Delta of X is called a [unk](q) set (1 < q < infinity) if for all trigonometric polynomials f = [unk](k=1) (n) alpha(k)chi(k) (chi(1),...,chi(n) [unk] Delta) an inequality parallelf parallel(q) [unk] [unk] parallelf parallel(1) obtains, where [unk] is a positive constant depending only on Delta. The subset Delta is called a Sidon set if every bounded function on Delta can be matched by a Fourier-Stieltjes transform. It is known that every Sidon set is a [unk](q) set for all q. For G = T, X = Z, Rudin (J. Math. Mech., 9, 203 (1960)) has found a set that is [unk](q) for all q but not Sidon. We extend this result to all infinite compact Abelian groups G: the character group X contains a subset Delta that is [unk](q) for all q, 1 < q < infinity, but Delta is not a Sidon set.

Journal Article↗

Method for determining whether the number of hepatocytes in rat liver is increased after treatment with the peroxisome proliferator gemfibrozil.

A histological method has been developed for determining the absolute numbers of rodent hepatocytes after treatment with the hypolipodemic drug gemfibrozil. It can be applied to distinguish between the enlargement of the liver that commonly occurs in rodents after treatment with chemicals, due to changes in the size of cells (hypertrophy), rather than an increase in the number of cells caused by cell division (hyperplasia). In the case of gemfibrozil the liver enlargement was found to be partly due to hypertrophy and partly to hyperplasia. The induction of hyperplasia can be associated with an increased risk of eventual liver tumour formation, and the distinction of hypertrophy from hyperplasia using a purely histological method, for the determination of increases in hepatocyte cell numbers, will be useful in the assessment of compounds which cause liver enlargement that could precede neoplasia.

Animals↗