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Biomedical subjects

H Ernst

Publications and source records attributed to H Ernst.

At least 55 records · Page 3Linked to original sources

Chemically induced pulmonary mucoepidermoid carcinoma in a female Wistar rat.

A case of a mucoepidermoid carcinoma, conventionally classified as an adenosquamous carcinoma, is described. The tumour bearing rat was exposed to a mixture of a pyrolized pitch condensate rich in polycyclic aromatic hydrocarbons and carbon black particles by inhalation for 10 months. The neoplasm was examined by conventional histopathologic procedures and by immunohistochemical detection of intermediate filaments. Morphologically, the tumour consisted of two components. The centre of the neoplasm was predominantly of adenocarcinomatous tissue and this was surrounded by keratinized squamous epithelium. The predominantly adenocarcinomatous component had a characteristic structural pattern consisting of one or a few layers of squamous epithelium covered by a continuous layer of mature goblet cells. The flattened cells were recognizable as squamous cells on the light microscopic level only after immunohistochemical staining with cytokeratin antibodies. Goblet cells and extracellular mucin were intensely positive for the PAS-reagent. This mucoepidermoid carcinoma in the rat was morphologically similar to those described in man. It is still unclear whether pulmonary mucoepidermoid carcinomas of humans originate from the bronchial epithelium or bronchial glands. It is most probable that the mucoepidermoid carcinoma of a rat described in this communication occurred by metaplasia in a carcinoma of bronchiolo-alveolar origin.

Animals↗

Ameloblastoma in a female Wistar rat.

A spontaneous ameloblastoma of the right mandible is described in a 120-week-old female Wistar rat (strain Chbb: THOM). The tumour had a locally aggressive growth pattern and was histologically characterized by sheets and islands of odontogenic epithelium bounded by a palisaded layer of ameloblast-like cells. Because of multifocal keratinizing squamous metaplasia of the stellate reticulum tissue, the tumour was classified as an acanthomatous ameloblastoma. Cyst formation, areas of stromal hyalinization and enamel matrix-like inclusions were further characteristics of the neoplasm. The epithelial elements stained strongly positive for broad spectrum cytokeratins.

Ameloblastoma↗

The interaction of the retina cell surface N-acetylgalactosaminylphosphotransferase with an endogenous proteoglycan ligand results in inhibition of cadherin-mediated adhesion.

We have previously shown that the binding to cells of a monoclonal antibody directed against the chick neural retina N-acetylgalactosaminylphosphotransferase (GalNAcPTase) results in inhibition of cadherin-mediated adhesion and neurite outgrowth. We hypothesized that the antibody mimics the action of an endogenous ligand. Chondroitin sulfate proteoglycans (CSPGs) are potential ligands because they inhibit adhesion and neurite outgrowth and are present in situ at barriers to neuronal growth. We therefore assayed purified CSPGs for their ability to inhibit homophilic cadherin-mediated adhesion and neurite outgrowth, as well as their ability to bind directly to the GalNAcPTase. A proteoglycan with a 250-kD core protein following removal of chondroitin sulfate chains (250-kD PG) inhibits cadherin-mediated adhesion and neurite outgrowth whether presented as the core protein or as a proteoglycan monomer bearing chondroitin sulfate. A proteoglycan with a 400-kD core protein is not inhibitory in either core protein or monomer form. Treatment of cells with phosphatidylinositol-specific phospholipase C, which removes cell surface GalNAcPTase, abolishes this inhibitory effect. Binding of the 250-kD core protein to cells is competed by the anti-GalNAcPTase antibody 1B11, suggesting that 1B11 and the 250-kD core protein bind to the same site or in close proximity. Moreover, soluble GalNAcPTase binds to the immobilized 250-kD core protein but not to the immobilized 400-kD core protein. Concomitant with inhibition of cadherin mediated adhesion, binding of the 250-kD core protein to the GalNAcPTase on cells results in the enhanced tyrosine phosphorylation of beta-catenin and the uncoupling of N-cadherin from its association with the cytoskeleton. Moreover, the 250-kD PG is present in embryonic chick retina and brain and is associated with the GalNAcPTase in situ. We conclude that the 250-kD PG is an endogenous ligand for the GalNAcPTase. Binding of the 250-kD PG to the GalNAcPTase initiates a signal cascade, involving the tyrosine phosphorylation of beta-catenin, which alters the association of cadherin with the actin-containing cytoskeleton and thereby inhibits adhesion and neurite outgrowth. Regulation of the temporal and spatial expression patterns of each member of the GalNacPTase/250-kD PG interactive pair may create opportunities for interaction that influence the course of development through effects on cadherin-based morphogenetic processes.

Animals↗

Epidermal growth factor and transforming growth factor-alpha: role in protection and healing of gastric mucosal lesions.

The maintenance of the integrity of the gastrointestinal mucosa and the repair of acute and chronic mucosal lesions are under the influence of various growth factors, especially epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha). EGF originates mainly from salivary glands, whereas TGF-alpha is released locally in the gastric mucosa, particularly when the mucosa is exposed to topical irritants. EGF and TGF-alpha have similar spectra of biological activity, which include the stimulation of the restitution and proliferation of mucosal cells, gastroprotection, vasodilatation, gastric adaptation to noxious substances, healing of acute and chronic lesions and inhibition of gastric acid secretion. Accumulation of EGF in the ulcer area as a result of excessive production by ulcer-associated new cell lineages contributes together with overexpression of EGF receptors in the ulcer area to the migration of cells from the ulcer margin and formation of granulation tissue and microvessels (angiogenesis) during the ulcer healing process.

Animals↗

Gastric adaptation to injury by repeated doses of aspirin strengthens mucosal defence against subsequent exposure to various strong irritants in rats.

Gastric adaptation to injury during repeated doses of acetyl salicylic acid (ASA) is a well documented finding but it is not known whether this adaptation affects the tolerance of the mucosa to other strong irritants. Gastric adaptation was induced by repeated daily doses of acidified ASA (100 mg/kg in 1.5 ml of 0.2 N HCl) given intragastrically (series A rats). Control rats with an intact stomach were given daily intragastric vehicle only (1.5 ml of 0.2 N HCl) (series B). After full adaptation to ASA (5 days), rats were challenged again with acidified ASA or, for comparison, with strong irritants such as 100% ethanol, 200 mM acidified taurocholate, or 25% NaCl for 1 hour or with water immersion and restraint for 3.5 hours. The first dose of ASA produced numerous gastric lesions and deep histological necrosis accompanied by a fall in the gastric blood flow, negligible expression of epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) or their receptors, and no evidence of mucosal proliferation. As adaptation to ASA developed, however, the areas of gastric lesions were reduced by more than 80% and there was a noticeable decrease in deep necrosis, a partial restoration of gastric blood flow, an approximately four-fold increase in EGF expression (but not in TGF alpha) and its receptors, and an appreciable increase in mucosal cell proliferation compared with vehicle treated rats. Increases in the mucosal expression of EGF receptors and the luminal content of EGF were also found in ASA adapted animals. In ASA adapted rats subsequently challenged with 100% ethanol, 200 mM TC, 25% NaCl, or stress, the area of the gastric lesions and deep histological necrosis were appreciably reduced compared with values in vehicle treated rats. This increased mucosal tolerance to strong irritants was also accompanied by the return of the gastric blood flow towards control levels and further significant increases in the mucosal expression of EGF receptors and mucosal cell proliferation. Gastric adaptation to ASA enhances the mucosal resistance to injury by strong irritants probably as a result of the restoration of the gastric blood flow and increased cell proliferation that may result from increased mucosal expression of EGF and its receptors.

Adaptation, Physiological↗

Partial orthotopic liver transplantation in rats.

A partial orthotopic liver transplantation technique (70% POLT) for use in rats and comparable with the corresponding recipient operation in the 'splitting transplantation' in man was developed. Body weight, liver function, histological and electron-microscopic findings were studied in comparison with whole rat liver transplantation with rearterialization, 30% POLT and corresponding liver resections. After 70 and 30% POLT typical signs of hepatic regeneration were found, but no pathological alterations in the electron-microscopic picture. This POLT model might be helpful for the investigation of unresolved questions in 'splitting transplantation'.

Animals↗

Receptor-mediated adhesive and anti-adhesive functions of chondroitin sulfate proteoglycan preparations from embryonic chicken brain.

Chondroitin sulfate proteoglycans inhibit the adhesion of cells to extracellular matrix proteins that otherwise permit adhesion. Although proteoglycans are widely assumed to act by masking the other protein in a mixed substrate, recent studies suggest that proteoglycans inhibit adhesion through mechanisms initiated by their binding to specific cell surface receptors. To explore this issue, we developed a purification scheme to isolate proteoglycan aggregates, monomers, and core proteins. Two distinct adhesion assays were used to study the interaction of these proteoglycan preparations with human foreskin fibroblasts: the gravity assay in which cell attachment is stabilized by cell spreading, and the centrifugation assay in which spreading does not play a role. All proteoglycan preparations mediate adhesion in the centrifugation assay but not in the gravity assay. In the centrifugation assay, proteoglycan aggregates and monomers are considerably more active than other extracellular matrix proteins while proteoglycan core proteins are at least as active as other extracellular matrix proteins. Proteoglycan core proteins bind to cell-associated hyaluronic acid, but not to integrins. Using mixed substrates in the gravity assay, all proteoglycan preparations inhibited cell attachment to fibronectin and vitronectin but not to collagen I and laminin. Although proteoglycan aggregates and monomers are more active than core proteins in inhibiting adhesion in the gravity assay, core proteins are still clearly active. A variety of control experiments suggest that the inhibition of cell attachment by proteoglycans is mediated through the specific interactions of proteoglycans with cell surface receptors, resulting in the inhibition of cell spreading. These results suggest at least two molecular mechanisms for proteoglycan-fibroblast interactions, one involving the chondroitin sulfate on the proteoglycan and an as yet unidentified receptor, the other involving the proteoglycan core protein and cell-associated hyaluronic acid.

Amino Acid Sequence↗

Granulomatous dermatitis and mastitis in two SPF rats associated with a slowly growing Staphylococcus aureus--a case report.

An isolated occurrence of multifocal severe granulomatous dermatitis and mastitis accompanied by extensive calcifications is described in 2 female Sprague-Dawley, SPF breeding rats. Poorly growing Staphylococcus aureus of uncertain lysotype (probably lysotype II) was isolated from the lesions of both rats. The source of infection could not be determined. No further cases in the closed barrier maintained breeding colony occurred in the following 7 months. Difficulties in interpreting these findings and the practical consequences relating to the hygienic status of the barrier breeding colony are discussed.

Animals↗

Distribution of extracellular matrix proteins in indomethacin-induced lesions in the rat stomach.

INTRODUCTION: We investigated the distribution of extracellular matrix (ECM) proteins in indomethacin-induced lesions of the rat stomach. METHOD: Twenty rats received indomethacin orally at a dose of 8 mg/kg/body weight. The animals were killed at 3, 6, 12, 24, and 48 h after administration of the drug. The stomachs were removed and frozen in liquid nitrogen. Cryostat serial sections of the lesions were immunostained with antibodies to collagen III, IV, and VI, laminin, and fibronectin. RESULTS: Fibronectin was the dominant extracellular protein of the provisional ECM in deep gastric lesions and gastric ulcers. Collagen III was strongly positive in stromal cells under the necrotic material in gastric erosions. Basal membrane proteins (collagen IV and laminin) were found to originate from the muscularis mucosae at the ulcer edge. CONCLUSION: There is a typical distribution of ECM proteins in erosions and ulcers of the rat stomach. Fibronectin was most prominent in the provisional matrix of gastric erosions and ulcers.

Animals↗

Neoplastic lung lesions in rat after chronic exposure to crystalline silica.

Groups of 100 SPF Fischer-344 rats were exposed 6 h a day, 5 d a week for 24 months to crystalline silica (1 mg center dot m-3, DQ 12 quartz) or titanium dioxide (5 mg center dot m-3) or air only. The animals were kept without further exposure for an additional 1.5 months. In the group exposed to crystalline silica a significantly increased incidence of 20 primary lung tumors was observed among 19 animals. The distribution of tumor types consisted of 3 adenomas, 11 adenocarcinomas, 4 benign cystic keratinizing squamous-cell tumors, 1 adenosquamous carcinoma, and 1 squamous-cell carcinoma. There were also 13 nodular hyperplasia lesions, which were interpreted to be borderline cases of adenomas. Approximately half of the adenoid tumors and all of the nodular hyperplasia lesions were characterized by moderate central fibrosis. The principal nonneoplastic findings in the silica-exposed group were lipoproteinosis, inflammation, epithelial hyperplasia, and fibrosis. The results can be considered significant due to the increased lung tumor incidence at a relatively low exposure level.

Administration, Inhalation↗

Solid-state nuclear magnetic resonance studies of acid sites in zeolites.

2H Magic-angle spinning nuclear magnetic resonance (MAS NMR), echo 27Al NMR, two-dimensional (2D) echo 1H MAS NMR and 1H, 27Al and 29Si MAS NMR have been applied to study the acid sites of dehydrated zeolites. The quadrupole coupling constants CQCC determined from 2H MAS NMR spectra of Si-OH-Al sites increase with the framework aluminium content of the zeolites from 208 Hz (H-ZSM-5) to 236 kHz (H-X and H-Y) due to the decreased acid strength of the bridging OH groups. The 27Al signal of the Si-OH-Al sites, which was considered "NMR-invisible" in the past, yields CQCC = 16 MHz for zeolite H-ZSM-5. The majority of non-framework aluminium species could also be observed in dealuminated and dehydrated zeolites H-ZSM-5 giving CQCC approximately 9 mHz. 2D echo 1H MAS NMR spectra yield values of 16-40 ms for the lower limits of the lifetime of hydroxyl species at room temperature. A lifetime of more than 40 ms was obtained from echo 2H MAS NMR spectra for protonated sites giving a signal at ca. 6.5 ppm in partially dealuminated and weakly rehydrated samples.

Aluminum↗

Induction of squamous cell carcinomas in the mouse lung after long-term inhalation of polycyclic aromatic hydrocarbon-rich exhausts.

A 10-month inhalation study using newborn female mice was performed to determine pulmonary tumorigenicity of polycyclic aromatic hydrocarbon (PAH)-enriched exhausts. At two exhaust doses containing 50 micrograms/m3 (group II) and 90 micrograms/m3 benzo(a)pyrene (BaP) (group III) a significant increase of lung tumors was observed and the incidence of malignant lung tumors was dose-dependent. Bronchiolo-alveolar adenomas were observed in all mice of groups II and III (40/40 each) as compared to 5/40 in the control (group I). Bronchiolo-alveolar adenocarcinomas developed in 10/40 and in 33/40 mice of groups II and III, respectively, but were absent in group I. Single or multiple squamous cell carcinomas, which showed variable degrees of differentiation were observed exclusively in 6 mice of group III. One adenosquamous carcinoma was seen in an further animal of this group.

Animals↗

Functional characterization of antiadhesion molecules.

Cytotactin, cytotactin binding (CTB) proteoglycan, and several other extracellular matrix (ECM) proteins and proteoglycans are described as antiadhesion molecules because they inhibit cell spreading and attachment to normally permissive ECM proteins. For cytotactin and CTB proteoglycan, this effect appears to be due to the binding of these proteins to their cell-surface receptors, which initiates a transmembrane signal that inhibits cell spreading. In contrast, the binding of fibronectin or laminin to its cell-surface receptors promotes cell spreading. Cell behavior may be regulated in a variety of systems by the interplay between these two opposing signals. For example, eosinophils on laminin spreading, form numerous foci containing filamentous actin, and remain viable in culture. In contrast, eosinophils on a mixture of laminin and cytotactin do not spread or form foci containing filamentous actin and the maintenance of viability is inhibited. In another system designed to model the immune surveillance of tumors, monocytes migrate in response to tumor necrosis factor through a gel comprised of a mixture of basement membrane proteins (Matrigel). Migration is blocked if the gel is coated with cytotactin. This result is of particular significance because cytotactin is expressed at high levels in the stroma of adult breast tissue surrounding tumors but only at low levels in normal breast tissue. These observations suggest that inflammation and the immune surveillance of tumors are among the processes regulated by cytotactin.

Animals↗

Morphological comparison between benign keratinizing cystic squamous cell tumours of the lung and squamous lesions of the skin in rats.

Approximately 700 cases of keratinizing cystic squamous lung lesions in rats were investigated by light microscopy in order to clarify the nomenclature and classification of these lesions. The structure of benign keratinizing cystic squamous cell tumours of the lung was compared to that of cystic squamous lesions in the skin of rats, with consideration of data from the literature. We conclude that the reviewed keratinizing cystic squamous cell lesions of the lung are true neoplasms and that the growth pattern of these cystic lesions is inconsistent with that of a simple cyst. In the development of squamous lung cancer, a continuum of proliferation from exaggerated metaplasia through benign cystic tumours to invasive squamous cell carcinomas can be observed.

Animals↗

Neuromuscular hamartoma (benign "Triton" tumour) in a mouse.

Histological examination of a 22-month-old CD-1 mouse revealed a threefold enlargement of the right trigeminal ganglion. This change was due to the presence of well-differentiated striated muscle fibers intermingling with nerves and ganglion cells. The number of ganglionic Schwann cells was also increased as demonstrated by their positive S-100 protein staining. In addition, slight interstitial mononuclear cell infiltration and fibrosis were observed. The myocytes, which stained positive for myoglobin and desmin, and the proliferated Schwann cells did not show any signs of cellular or nuclear atypia. The lesion was diagnosed as "neuromuscular hamartoma (benign "Triton" tumor)" reflecting the capability of either Schwann cells or neural crest derived precursor cells to differentiate into various other cell types.

Animals↗