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Biomedical subjects

A Reith

Publications and source records attributed to A Reith.

At least 37 records · Page 2Linked to original sources
PubMed1988

Modification of surfactant metabolizing cells in rat lung by clofibrate, a hypolipidemic peroxisome proliferating agent. Evidence to suggest that clofibrate influences pulmonary surfactant metabolism.

The influence of clofibrate (ethyl-alpha-p-chlorophenoxy-isobutyrate), a hypolipidemic peroxisome proliferating agent, has been tested on the lungs of adult male rats. Drug administration for 7 days caused structural changes in two types of lung cells, both of which are involved in the metabolism of the pulmonary surfactant. By light microscopy the prominent features were the presence of enlarged type II alveolar epithelial cells and foamy intraalveolar macrophages. Compared with controls, type II cells in treated rats apparently contained more numerous surfactant-containing lamellar bodies, as visualized in semi-thin sections of Epon-embedded tissue. This difference was quantified morphometrically by light microscopy: the number of lamellar bodies was estimated as the profile number per individual type II alveolar cell, transsected at its nucleus. Clofibrate administration for 7 days resulted in a significant increase in the number of the lamellar inclusions. In contrast the number of type II alveolar cells per area of lung remained unchanged. There was no evidence of atelectasis or inflammatory infiltration in the drug-treated lungs, a finding confirmed in sections of perfusion-fixed, paraffin-embedded whole lung-lobes. By electron microscopy the lamellar inclusion bodies in the type II alveolar cells in treated rats, apart from being more numerous and sometimes smaller, were morphologically identical to those in controls. The vacuolated alveolar macrophages seen in treated rats also contained various lamellar phospholipid inclusions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Two hypolipidemic peroxisome proliferators increase the number of lamellar bodies in alveolar cells type II of the rat lung.

Male rats treated with either clofibrate or nafenopin, two peroxisome proliferating compounds with potent hypolipidemic properties, show identical structural changes in their lungs. In both cases, two types of lung cells were affected by these agents: (i) the alveolar epithelial cells type II and (ii) the intraalveolar macrophages. These lung cells are known to be involved in the metabolism of the pulmonary surfactant which serves to reduce the surface tension within alveoli. The size of the alveolar cells type II was conspicuously increased in the treated lungs. Compared to controls, intraalveolar macrophages apparently were slightly more numerous. Their enlarged cytoplasm was strongly vacuolated. The osmiophilic lamellar bodies within alveolar cells type II represent the intracellular presecretory pulmonary surfactant. Their number per individual alveolar cell type II was estimated by means of light microscopic morphometry on Epon-embedded semithin sections. Compared to control lungs, the number was increased by about 30% in rats treated with clofibrate (11.4 +/- 0.5 lamellar inclusions in the control cells; P less than 0.001). The increase in the number of lamellar bodies per type II cell was close to 60% in animals fed the nafenopin diet. In contrast the frequency of alveolar cells type II, estimated per area of lung tissue, remained unchanged. These results demonstrate that clofibrate and nafenopin, two drugs with hypolipidemic properties, cause identical structural changes in the rodent lung. It is concluded from these data that (i) the morphological changes observed in the surfactant metabolizing cells represent a specific action of hypolipidemic agents at the lungs and (ii) hypolipidemic peroxisome proliferators influence the metabolism of the pulmonary surfactant.

Animals↗
PubMed1988

Ploidy distribution in experimental liver carcinogenesis in mice.

There have been several reports on the distribution of DNA in premalignant and malignant liver cells after carcinogen treatment in rodents. The most striking result so far is that ploidy distributions seems to depend more on experimental protocols and less on carcinogenesis per se. The present study demonstrates that an evaluation by means of flow cytometry and stereological image analysis yields results showing similar ploidy distributions throughout the known sequence of tissue changes seen during liver cancer development. Furthermore, our results demonstrate inter-individual differences between the lesions in each of the steps in these tissue changes, (foci, nodules and hepatocarcinomas). The present study gives no reason to conclude that changes in ploidy distribution are essential in liver carcinogenesis.

Animals↗
PubMed1988

Clofibrate increases the number of peroxisomes and of lamellar bodies in alveolar cells type II of the rat lung.

The hypolipidemic drug clofibrate, which causes a striking proliferation of hepatic peroxisomes, and the induction of peroxisomal lipid metabolizing enzymes, was tested for its influence on rat lung. Alveolar cells type II of the lung are the major source of the surface-active phospholipid-apoprotein complex. Their surfactant-containing lamellar bodies are part of the pulmonary surfactant system. To test the possible relationship between lung peroxisomes and the phospholipid-rich lamellar bodies in alveolar cells type II, clofibrate was administered to male rats. Drug treatment for 7 days resulted in a 30% (p less than 0.001) increase in the number of lamellar bodies within the type II cells, as estimated by morphometry on semithin sections of the lung. In contrast, the average number of type II cells per area of lung remained unchanged which indicates that type II cell proliferation did not occur. Intraalveolar macrophages were consistently vacuolated and markedly increased in size in the lungs of the treated rats. Peroxisomes (microperoxisomes) were identified cytochemically using the alkaline diaminobenzidine (DAB) method for catalase, a marker enzyme of these organelles. Ultrastructural-morphometric analysis of the lungs showed that clofibrate treatment resulted in a 60% increase in the profile number of DAB-positive peroxisomes (p less than 0.005) in alveolar cells type II which are known to be actively involved in the synthesis of the pulmonary surfactant. The number of mitochondria remained unchanged. A great variation in shape and size of the proliferated peroxisomes was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Keratin and involucrin in preneoplastic and neoplastic lesions. Distribution in the nasal mucosa of nickel workers.

Nasal mucosal biopsy specimens encompassing normal and pathological epithelia were obtained from nickel workers, a population with an increased incidence of carcinomas of the respiratory tract. The immunohistochemical detection of keratins was carried out using monoclonal antibodies AE1 and AE3. The antibody AE1 stained only the basal cells of normal mucociliary epithelium. Regular metaplasias showed an increased stain with AE3; all layers of the surface epithelium were stained. The dysplastic and neoplastic lesions exhibited an extraordinary increase in the staining patterns with AE3 and to a lesser extent with AE1. Involucrin, which was absent from the normal pseudostratified epithelium, appeared in all metaplastic-dysplastic lesions and in keratinized areas of carcinomas. The combined detection of keratins and involucrin proved useful in detecting the degree of maturity and differentiation of preneoplastic and neoplastic lesions of the nasal mucosa.

Antibodies, Monoclonal↗
PubMed1986

A method for determining ploidy distributions in liver tissue by stereological analysis of nuclear size calibrated by flow cytometric DNA analysis.

A method is presented for determining ploidy distributions in mouse liver from image analysis with stereological estimations of nuclear size in tissue sections. Nuclear profile distributions obtained from profile measurements were subjected to a mathematical unfolding procedure in order to obtain the nuclear size distributions. Based on the assumption that nuclear size increases monotonically with nuclear DNA content, flow cytometric DNA analysis of suspensions of liver cell nuclei was used to calibrate the method, thus yielding the mean nuclear size of each ploidy class, i.e., diploid, tetraploid, and octaploid nuclei. After the size interval for each of the ploidy classes was determined, the method allowed determination of ploidy distributions in mouse liver by stereological image analysis alone. The method was established from combined stereological and flow cytometric measurements on liver tissue representing two different stages of liver regeneration after two-thirds partial hepatectomy, and it was tested against an independent set of data representing a marked increase in the portion of S-phase cells.

Animals↗
PubMed1986

An epidermal proliferative unit-like structure in the epithelium of mouse bladder observed by backscattered electron imaging.

The simultaneous use of a silver-staining technique, backscattered electron imaging and stereo-tilts has made it possible to visualize the spatial distribution of cell nuclei in the stretched epithelium of the bladder of mice. This study has led to the observation that a structural organization resembling the epidermal proliferative unit, previously found in the skin exists also in bladder epithelium. However, the proliferative unit in the bladder was different in that it contained a higher number of cells per unit, and an absence of columns of inactive squamous cells. These findings may indicate that epidermal proliferative unit-like structures represent a common form of organization in some epithelia.

Animals↗
PubMed1986

Direct preparation and G-banding of chromosomes of mouse liver cells.

A method has been developed for the direct preparation and G-banding of chromosomes of mouse liver cells by combining the techniques of liver perfusion and preparation of G-banded chromosomes with partial hepatectomy and colcemid treatment of the animal. The results indicate that cytogenetic investigations of isolated preneoplastic liver cells are possible. The method offers an increased possibility for the use of the liver as an in vivo test system for mutagens and carcinogens.

Animals↗
PubMed1986

The interaction between cell-surface antigens and antibodies bound to monodisperse polymer particles in normal and malignant cells.

The interaction between polymer particles with an immune ligand on their surfaces and normal (hepatocytes) and malignant (Raji) cells with a corresponding membrane receptor was investigated by scanning and transmission electron microscopy. The influence of time, temperature, and anti-metabolites on this process was studied. The results indicate that when particles with an immunoligand are added to cells with a corresponding membrane receptor, three successive steps are initiated, the first two of which are not dependent on the temperature or the metabolic state of the cells. The first step in this process is the binding of particles to the cell surface through the immunoligand on the particle and the receptor on the cell surface. The initial binding formed by immunoligand and corresponding receptor is followed by a stronger interaction between cell and particle. This second step seems to be governed by a successive antibody-antigen interaction: the zipper mechanism. A third step in the particle-to-cell interaction is characterized by movements of the cellular surface, as revealed by membrane folds, pseudopods, and lamellae extending from the surface and enveloping large parts of the particle.

Antigen-Antibody Reactions↗
PubMed1986

Spatial visualization of junctional complexes by backscattered electron imaging and silver staining.

A method for the observation of junctional complexes by backscattered electron imaging in scanning electron microscopy, in tissue blocks, is presented. The junctional complexes are revealed by a modified silver staining method (originally devised for nucleolar organizer regions), used "en bloc" after formalin or glutaraldehyde fixation. Backscattered electron imaging allows, after this staining, the observation of junctional complexes through the surface of intact superficial cells, in the three tissues studied (liver, jejunum and urinary bladder). The interest of this approach is to offer the possibility of observing junctional complexes "by transparence," in nondissociated and nonsectioned tissues.

Animals↗
PubMed1985

Ultrastructural and cytochemical study of the early stages of liver colonization by transplanted neoplastic hepatocytes.

Neoplastic liver cell colonies were induced in the livers of isogeneic F344 rats by intraportal injection of a hepatic cell suspension from diethylnitrosamine-treated donor rats. Examination of the livers 12 days after cell implantation revealed well-demarcated groups of liver cells. The colonies showed alterations of the normal hepatocyte phenotype, which were clearly demonstrated by histologic, cytochemical, and electron microscope techniques. The hepatocytes were markedly deficient in glucose-6-phosphatase and bile canalicular ATPase activities, and they contained numerous mitotic figures. Scanning and transmission electron microscopy allowed characterization of hepatocyte interfaces and the shape of sinusoids and the biliary network. The nodular colonies displayed disorganized, thickened trabeculae separated by dilated sinusoids. In these colonies the hepatocytes proliferated intensely and formed, inside the host parenchyma, revascularized, integrated nodular structures. However, these hepatocytes showed ultrastructural anomalies: large nuclei with prominent nucleoli, many free polysomes, and areas of proliferated smooth endoplasmic reticulum in connection with unfolded cisternae of the rough endoplasmic reticulum. All of these features agreed with the hypothesis previously proposed that the colonies may be precursors of the hepatocarcinomas that ultimately develop in animals given injections of treated liver cells. Direct confirmation, however, still is needed.

Adenosine Triphosphatases↗
PubMed1977

Ammonia inhibits protein secretion in isolated rat hepatocytes.

The general secretion of proteins by isolated rat hepatocytes in suspension is inhibited by colchicine, anoxia, or ammonia (NH4Cl). The inhibition by ammonia is accompanied by the cytoplasmic retention and swelling of protein secretory vesicles, suggesting that ammonia accumulates in the vesicles and thereby prevents their translocation to the cell periphery. General protein synthesis appears to be relatively unaffected by ammonia.

Ammonia↗
PubMed1977

Morphometry and ultrastructure of prismatic cristae in mitochondria of a crayfish muscle. A hypothesis of the structural principle.

Approximately 40% of the mitochondria in the sphincter muscle of the crayfish vas deferens have prismatic-type cristae. In cross section, the angular cristae have either triangular or rhomboid profiles which are surrounded by a hexagonal array of electron-dense dots. In longitudinal section, these mitochondria exhibit both thick and thin parallel lines, which represent cristae and filaments, respectively. It is postulated that the matrix of the prismatic-type mitochondria is packed with rodlets composed of an electron-dense core and a less dense shell. Close packing of these rodlets results in the regular hexagonal dot array. Deletion of fascicles of 3 or 4 rodlets results in spaces with triangular or rectangular cross sections. Lining of these spaces with membranes results in cristae with triangular or rhomboid cross sections.

Animals↗