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  • 11
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 87 (1976), S. 199-212 
    ISSN: 1432-1335
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Durch orale Applikation von MNNG (N-methyl-N′-nitro-N-nitrosoguanidin) über 35 Wochen oder ENNG (N-äthyl-N′-nitro-Nnitrosoguanidin) über 20 Wochen wurden experimentelle Carcinome im Drüsenmagen von Ratten erzeugt. Die Tiere wurden in regelmäßigen Abständen nach dem Fütterungsbeginn getötet und die Tumoren histologisch aufgearbeitet. Dadurch waren die Entwicklungsphasen der Carcinogenese analysierbar, die für die Frühdiagnose des Magencarcinoms von Bedeutung sein können. Die histologischen Veränderungen während der Carcinogenese wurden in 4 Stadien eingeteilt : 1. Die regenerative Hyperplasie findet sich 1–9 Wochen nach Fütterungsbeginn mit MNNG vorwiegend im Bereich von Erosionen und Geschwüren. Es handelt sich um unregelmäßige Drüsenproliferationen ohne Zellatypien. 2. Die glanduläre Hyperplasie, die am häufigsten 12–17 Wochen nach MNNG-Gabe auftritt, besteht aus einer verdickten Schleimhaut mit vermehrten Drüsenschläuchen, die ebenfalls gut ausdifferenziert sind und kaum Atypien zeigen. 3. Die Dysplasie zeigt sehr unregelmäßige Drüsen mit ausgeprägten Zellatypien, deren Ausdehnung jedoch auf die Schleimhaut beschränkt ist. 4. Die Neoplasien bestehen aus undifferenzierten Drüsenproliferationen, die bis in die Tunica serosa vordringen. Zum Teil handelt es sich noch um Adenome, meist jedoch um Adenocarcinome. In einigen Fällen waren Metastasen in Pankreas, Leber und Lymphknoten nachweisbar, in einem Fall in einer Rippe. Histochemisch zeigten die Tumoren im Vergleich zu den Kontrollen keine charakteristischen Veränderungen.
    Notes: Summary Experimental carcinomas in the glandular stomach of rats were induced by oral administration of MNNG (M-methyl-N′-nitro-N-nitrosoguanidin) for 35 weeks or ENNG (N-ethyl-N′-nitro-N-nitrosoguanidin) for 20 weeks. Rats were killed at different times after beginning of carcinogen treatment and tissue specimens were prepared for histologic investigation. Particular interest was placed on the development of tumors and on pathological findings possibly contributing to early diagnosis of stomach cancer. During the development of tumors, several dysplastic reactions were observed in the antral mucosa. They could be classified into 4 groups : One was regenerative hyperplasia (1) that meant irregular glandular proliferations without cell atypism at the margin of erosions and ulcers. This lesion was mainly found 1–9 weeks after administration of MNNG. In glandular hyperplasia (2) either crypts or glands were extended and mucosal layers were thickened. No signs of cell atypism were observed. This lesion was mainly found 12–17 weeks after administration of MNNG. Dysplasia (3) was combined with considerable structural modifications and cellular atypism. However, this lesion was limited to the mucosal layer. Neoplastic changes (4) were characterized by marked cellular atypism and extension to tunica submucosa and tunica serosa. Some tumors showed the histological patterns of benign tumors, but most of them were adenocarcinomas. In some cases metastases into pancreas, liver and lymph nodes and in one case into the 12th rib were observed. No particular enzyme patterns were found by histochemistry.
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 87 (1976), S. 213-228 
    ISSN: 1432-1335
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung In der vorliegenden Arbeit wurden durch MNNG (N-methyl-N′-nitro-N-nitrosoguanidin) oder ENNG (N-ethyl-N′-nitro-N-nitrosoguanidin) erzeugte Tumoren im Drüsenmagen der Ratte feinstrukturell untersucht. Ziel der Untersuchung war es, die Polymorphie der Tumorzellen in dem experimentellen Carcinom zu beschreiben und insbesondere die Beziehungen zwischen den verschiedenen metaplastischen Zelltypen und den Carcinomzellen zu untersuchen. Im Tumorgewebe konnten besonders im Invasionsbereich neben undifferenzierten Adenocarcinomzellen zahlreiche gut differenzierte Zellen nachgewiesen werden. Es fanden sich Becherzellen, endokrine Zellen, Zellen, die lamellierte Myelinfiguren in ihrem Cytoplasma enthielten und Plattenepithelcarcinomzellen. Vor allen Dingen wurden regelmäßig Zellen mit gut differenzierten Mikrovilli beobachtet, die Tonofilamente und den “membrane coating granules” ähnliche Granula enthielten und somit typische Zeichen sowohl des Plattenepithels als auch der Drüsenzellen aufwiesen. Daher wurden diese Zellen als Zwischenstufen zwischen Adenocarcinomzellen und Plattenepithelcarcinomzellen gewertet. Das Vorkommen derartiger Zwischenstufen scheint uns darauf hinzuweisen, daß Adenocarcinomzellen in dem durch MNNG oder ENNG erzeugten experimentellen Magencarcinom die Fähigkeit besitzen können, sich nach Zellteilung zu den genannten metaplastischen Zelltypen zu differenzieren.
    Notes: Summary In the present study electron microscopic investigations of tumors of the glandular stomach of rats induced by oral administration of MNNG or ENNG are dealt with. The aim of the study was to describe the different cell types found in the carcinoma and to elucidate the possible realtionship between the undifferentiated carcinoma cells and the more differentiated cell types found in the tumor. The results show that besides undifferentiaded carcinoma cells, several differentiated cell types such as goblet cells, endocrine cells, cells with lamellated inclusions in their cytoplasm, and squamous carcinoma cells can be observed. The most conspicuous findings were carcinomatous gland cells with well differentiated microvilli on their luminal surface and typical tonofilamentous structures in their cytoplasm. These cells exhibited signs of the squamous epithelium and of gland cells. Therefore they may be considered as intermediate variants between adenocarcinoma cells and squamous carcinoma cells. The occurrence of such intermediate steps points to the possibility of differentiation by cell division of adenocarcinoma cells into several metaplastic cell types in the experimental stomach carcinoma induced by MNNG or ENNG.
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  • 13
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 91 (1978), S. 323-334 
    ISSN: 1432-1335
    Keywords: Bursectomy ; Chicken ; Benzypren-Sarcoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 160 chickens hormonally bursectomized before hatching, and 160 controls were twice given a dose of 10mg 3,4-benzo(a)pyrene 2 weeks and 6 weeks after hatching. After 24 weeks the controls had developed muscle sarcomas at a significantly higher rate than the bursectomized animals (49.6–32.1%). The tumors were identified as malignant polymorphocellular rhabdomyosarcomas in light and electron microscopy. When the experiment was stopped after 27 weeks, the controls showed more tumors than the bursectomized chickens (65.1% versus 58.9%). The effect of bursectomy lies in a prolongation fo tumor latency. The frequency of metastases is equally decreased to a significant degree (41.7% versus 21.7%). These results are interpreted as an illustration of the disturbed equilibrium between the T and B cell responses.
    Type of Medium: Electronic Resource
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  • 14
    ISSN: 1432-2307
    Keywords: Human atherosclerotic plaque ; Phenotypic characterization of cell types ; Monoclonal antibodies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sections of human atherosclerotic plaques, obtained from 21 autopsy cases with various degrees of atherosclerosis, were stained with the indirect immunoperoxidase technique using specific monoclonal antibodies against macrophages and smooth muscle cells. Distinctive results were found in differing stages: Single blood monocytes were observed in diffuse intimal thickening and the foam cells seen in fatty streaks were mostly identified as mature tissue macrophages, while only very few blood monocytes were present. The spindle cells observed in fibroelastic plaques showed positive reactions to antibodies against desmin, which points to their derivation from smooth muscle cells, whereas only a few macrophage-derived foam cells were seen in these lesions. In the complicated lesions the majority of foam cells were macrophage-derived, but there was also a small number of foam cells positive to antibodies against desmin, suggesting a smooth muscle cell derivation. - Our results confirm that in human atherosclerotic plaques the majority of the foam cells are obviously macrophage-derived, which emphasizes the important role of macrophages in the morphogenesis of these lesions.
    Type of Medium: Electronic Resource
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  • 15
    ISSN: 1432-1912
    Keywords: Phalloidin poisoning ; Isolated hepatocytes ; 4,4′-diisothiocyano stilbene-2,2′-disulfonic acid ; Plasma membranes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 4,4′-Diisothiocyano stilbene-2,2′-disulfonic acid (DIDS) inhibits the typical development of protrusions, regularly seen after treatment of isolated hepatocytes with phalloidin. The degree of inhibition depends on the time of preincubation and on the concentration of DIDS, but not on the concentration of phalloidin. DIDS is more effective than H2DIDS. The inhibition by both compounds is irreversible. The binding capacity of hepatocytes for H2DIDS is much higher than that of the phalloidin-insensitive hepatoma cells. Gel electrophoresis of lysates from cells, pretreated with 3H2DIDS demonstrates that actin binds very little of the inhibitor. Our results suggest that a protein structure on the surface of hepatocytes, needed for the response to phalloidin, is influenced by DIDS or H2DIDS.
    Type of Medium: Electronic Resource
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  • 16
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 305 (1978), S. 253-259 
    ISSN: 1432-1912
    Keywords: Phalloidin poisoning ; Isolated hepatocytes ; AS-30D hepatoma ; Contractile proteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In contrast to normal liver cells, AS-30D hepatoma cells are insensitive to phalloidin. The lack of the typical phalloidin response in the latter cells is not due to a deficiency of contractile proteins. Actin prepared from hepatoma cells is able to form filamentous structures and is stabilized in a manner similar to muscle actin. Isolated liver cells were exposed to a medium containing phalloidin and removed after 20 min by centrifugation. The supernatant was inculated again with fresh cells. The procedure was repeated four times. The phalloidin response decreased to about 19% of the control because of the uptake of phalloidin during each incubation. When the same procedure was carried out with AS-30D hepatoma cells, and aliquots of the supernatants were tested with hepatocytes no marked decrease of the phalloidin response was seen. This indicates that hepatoma cells do not consume the toxin as do normal liver cells.
    Type of Medium: Electronic Resource
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  • 17
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 59 (1981), S. 931-941 
    ISSN: 1432-1440
    Keywords: Malignant invasion ; Metastazation ; Nuclear dedifferentiation ; Carcinogenesis ; Maligne Invasion ; Metastasierung ; Zellkern-Entdifferenzierung ; Carcinogenese
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei der Analyse der malignen Wucherungen steht außer der hohen Wachstumsgeschwindigkeit der Tumorzellen die Histolyse, d.h. aggressive, lytische Mechanismen, mit denen sich bösartige Tumorzellen in die Umgebung vorschieben, im Vordergrund. Ein spezifisch gegen Typ-IV-Kollagen gerichtetes Enzym spielt hier eine bevorzugte Rolle. Hinzu kommt eine Auto-Lokomotion der Tumorzellen. Diese Eigenschaften erklären auch die Metastasierung, die als hoch-selektiver Prozeß in mindestens drei Schritten abläuft: Invasion in ein Blut- oder Lymphgefäß, Verschleppung in Blut- oder Lymphbahnen und Infiltration in ein fremdes Gewebe nach Destruktion der Gefäßwand. Unter den Faktoren, welche die Metastasierung leiten, spielen die Blutgerinnung und die Zusammensetzung der Tumoren aus verschieden malignen Subpopulationen eine führende Rolle. Grundlage all dieser Kennzeichen des malignen Wachstums ist ein Verlust der differenzierten Funktionsleistung der Zellen, faßbar z.B. an einem Verlust der gewebsspezifischen Chromatinstruktur der Zellkerne. Die auslösenden Faktoren der Tumorentstehung, die sog. Primärfaktoren, greifen durchweg an der DNA, also am Genom an. Sowohl chemische Carcinogene als auch Viren und vor allem auch kurzwellige und ionisierende Strahlen verursachen DNA-Defekte, die allerdings in den meisten Fällen durch Reparationsmechanismen korrigiert werden. Danach ist die Entstehung eines bösartigen Tumors letztlich ein Versagen dieser DNA-Reparationsmechanismen. Begünstigende Cofaktoren der Carcinogene bewirken eine Verkürzung der Latenzphase. Hierzu gehören verschiedene spezifische chemische Substanzen und Hormone. Nachdem wir wissen, daß bösartige Tumoren lange Zeit „schlafend“ im Gewebe ruhen können, ergibt sich eine neue Gliederung des zeitlich-gestaltlichen Ablaufes der Carcinogenese, wobei nach Ausbildung des Primärtumors im einzelnen noch nicht bekannte Wachstumsfaktoren und vor allem immunologische Faktoren für die Entstehung der eigentlichen Tumorkrankheiten verantwortlich zu sein scheinen.
    Notes: Summary Analysis of invasive malignancy focuses on the particularly high growth rate of tumor cells, and on the aggressive mechanisms of histolysis favoring the infiltration of the malignant cells into the surrounding tissue. Specific significance is attributed to a certain enzyme directed against type IV collagen, and to the auto-locomotion of tumor cells, properties that may also explain the highly selective process of metastazation in at least three consecutive steps: Tumor cells invade a blood or lymph vessel, they are transported along blood or lymphatic pathways, and they eventually infiltrate foreign tissue after penetration and destruction of blood or lymph vessel walls. Among the factors involved in the process of metastazation, special interest is due to blood coagulation and to the coexistenxe of different dumor cell subpopulations within a primary. These features of malignant growth are based on the loss of functional differentiation as manifested e.g. in the loss of tissue-specific nuclear chromatin structures. Tumor development is triggered by the so-called primary factors which always affect the DNA, i.e. the cell genome. Chemical carcinogens, viruses, and shortwave or ionizing irradiation induce DNA defects which, however, will be reversed and mended by special repair mechanisms in most cases. Thus, the actual development and spread of malignancy is ultimately due to deficient reparation. Co-factors favorizing and promoting carcinogenesis may shorten the latency period, among other several specific chemicals and hormones. Based on current knowledge of tumor dormany a new concept is proposed for the chronological and morphological sequence of carcinogenesis: Following the development of a primary tumor certain as yet undefined growth factors and especially immunological factors may be responsible for the development of a progressive tumor disease.
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  • 18
    Electronic Resource
    Electronic Resource
    Springer
    Der Pathologe 20 (1999), S. 267-275 
    ISSN: 1432-1963
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 19
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 317 (1981), S. 364-367 
    ISSN: 1432-1912
    Keywords: Isolated hepatocytes ; Phalloidin ; Ligandin ; Protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To exclude an involvement of ligandin in the uptake and storage of phalloidin in hepatocytes equilibriumdialysis studies were made with phalloidin, cholic acid and bromosulfophthalein (BSP). Binding studies with isolated ligandin indicated that the affinity of ligandin for phalloidin is low (K D=0.8×10−3 M). Phalloidin neither displaced BSP (K D=1.3×10−7M) or cholic acid (K D=7.6×10−5 M) from ligandin, when preloaded with these substrates. Hepatocytes prepared from rats after daily treatment with phenobarbital during 5 days contained 3–4-fold concentrations of ligandin and bound greater amounts of BSP than controls. Nevertheless the velocity of the uptake both of [3H]-demethylphalloin ([3H]-DMP) and of [35S]-BSP was not augmented. Also the sensitivity of liver cells to phalloidin was not drastically modified after induction with phenobarbital and agrees with earlier findings in vivo. We conclude that ligandin plays a negligible role in the uptake and a minor role in the storage of phallotoxins in liver cells.
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  • 20
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 306 (1979), S. 295-300 
    ISSN: 1432-1912
    Keywords: Phalloidin ; Baby rats ; Regenerating liver ; Carbon tetrachloride ; Actin ; Bile acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Isolated hepatocytes, prepared from 5 day old rats, from regenerating livers or from livers after poisoning with carbon tetrachloride, are less sensitive to phalloidin in vitro than hepatocytes from untreated adult controls. The time course of the reduced susceptibility to phalloidin was compared with the ability of hepatocytes to take up bile acids under various conditions. SDS-electrophoresis of cell lysates gave no evidence for decreased levels of actin in cells with reduced sensitivity to phalloidin. In contrast, there was a good relationship between the active uptake of bile acids and the sensitivity of hepatocytes to phalloidin. The decreased response of hepatocytes from baby rats, from regenerating livers or from poisoned livers to phalloidin is more probably related to differences in phalloidin uptake than to a reduced endowment with microfilamentous structures.
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