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  • 1
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Experimental Cell Research 93 (1975), S. 472-477 
    ISSN: 0014-4827
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Cell Biology International Reports 2 (1978), S. 87-98 
    ISSN: 0309-1651
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2307
    Keywords: Renal carcinogenesis ; Epithelial kidney tumours ; Energy metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Renal oncocytomas, which have previously been shown to originate from the collecting duct system, were induced in male Sprague-Dawley rats by oral administration of N-nitrosomorpholine (NNM) for 7 weeks. The expression of glucose transporter isoforms GLUT1 and GLUT2, and of several enzymes involved in glucose metabolism [hexokinase (HK), pyruvate kinase (PK), lactate dehydrogenase (LDH), malate dehydrogenase (MDH)] were studied by cytochemical approaches in serial cryostat sections of the kidney 12, 23 and 34 weeks after withdrawal of NNM. Oncocytic tubules connected with collecting ducts were first observed 23 weeks, and oncocytomas 34 weeks after withdrawal. The cytochemical pattern of oncocytic tubules and oncocytomas was similar, but differed markedly from that of normal collecting ducts in nearly all variables studied; expression of GLUT1 and hexokinase I proteins were strongly increased; activities of HK, PK and MDH were elevated, while LDH activity was reduced. These results suggest that oncocytic transformation is associated with fundamental changes in energy metabolism which differ from those in cell lineages leading to other types of renal cell tumours, such as clear/acidophilic and basophilic cell tumours. The characteristic over-expression of GLUT1 may be used as a diagnostic criterion for the discrimination between oncocytes and acidophilic (granular) cells in clear/acidophilic renal cell tumours which show a reduced expression of this glucose transporter protein.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Planta 114 (1973), S. 239-250 
    ISSN: 1432-2048
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The ultrastructure of the “primary” nucleus of the marine green algae Acetabularia (Polyphysa) cliftonii as revealed by the freeze-etching technique is described. The nuclear envelope is perforated by about 3×106 pores which appear arranged nearly in rows. The nucleus is covered with a layer of cytoplasm which protects it in the isolated state and resists various manipulations. This cytoplasmic layer is protected by an elementary membrane. The latter appears rough on the cytoplasmic side, and smooth on the side facing the “cell sap”. The cytoplasmic layer and the surrounding perinuclear cytoplasm are connected by cytoplasmic ducts. The nucleus appears irregularly shaped owing to many invaginations in the nuclear envelope. Sometimes mitochondria are observed in these cavities.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 92 (1978), S. 63-86 
    ISSN: 1432-1335
    Keywords: Neoplastic transformation ; Glycogenosis ; Lipidosis ; Mitochondria ; Interstitial cells ; Neoplastische Transformation ; Glykogenose ; Lipidose ; Mitochondrien ; interstitielle Zellen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Genese klarzelliger und acidophilzelliger (granuliertzelliger) Nierentumoren wurde in Stoppversuchen an Nitrosomorpholin-vergifteten Ratten stufenweise licht und elektronenmikroskopisch untersucht. Am Ende der 3–14 wöchigen Vergiftungsphase sind in den Nieren der Versuchsratten morphologisch keine Unterschiede gegenüber den Kontrollen festzustellen. Einige Wochen nach Absetzen des Carcinogens entwickelt sich jedoch in einzelnen Nierentubuli häufig eine exzessive Glykogenspeicherung (tubuläre Glykogenose), die nach einer Latenzzeit von 22–97 Wochen mehr als 50% der Versuchstiere betrifft. Während des gleichen Zeitraumes bilden sich bei 25–30% der Versuchstiere klarzellige und/oder acidophilzellige (granuliertzellige) Nierentumoren aus. Von den glykogenotischen Tubuli, die vereinzelt schon 3 Wochen nach Absetzen des Carcinogens zu beobachten sind, führen alle Übergänge zu den klaroder acidophilzelligen Tumoren. Die tubuläre Glykogenose wird daher als eine präneoplastische Läsion aufgefaßt. Die Tumoren enthalten neben den kennzeichnenden klaren Zellen vor allem lipidspeichernde und mitochondrienreiche (granulierte) Zellen. Die Feinstruktur der Tumoren weist auf eine Abstammung von differenzierten Nierentubuli hin. Das Glykogen der klaren Zellen liegt überwiegend im Grundplasma, daneben auch in autophagen Vakuolen. Die Lipide bilden dichte Körper, die ein regelmäßiges Linienmuster mit einer Periodik von 5–7 nm aufweisen. Die Mitochondrien der Tumorzellen, besonders jene der acidophilen Zellen, zeichnen sich oft durch einen Mangel an Cristae aus. Mitunter finden sich große cristaarme, jedoch matrixreiche Mitochondrien. In alle klarzelligen Nierentumoren sind interstitielle Zellen eingestreut, die reichlich saure Mucopolysaccharide speichern. Es wird angenommen, daß die zellulären Thesaurismosen (Glykogenose, Lipidose, Mucopolysaccharidose) Störungen des Zellstoffwechsels anzeigen, die in engem Zusammenhang mit der Geschwulstbildung stehen.
    Notes: Summary The genesis of clear and acidophilic (granular) cell kidney tumors was investigated by light and electron microscopy in rats treated for a limited time (stop experiment) by N-nitrosomorpholine. At the end of the period of treatment (3–14 weeks) the kidneys of the experimental animals were morphologically unchanged as compared to the controls. However, some weeks after cessation of the carcinogenic treatment an excessive storage of glycogen (glycogenosis) in single tubules was frequently found. After a lag period of 22–97 weeks, the tubular glycogenosis affected more than 50% of the experimental animals. During the same period clear and/or acidophilic cell (granular cell) kidney tumors developed in 25–30% of the animals. All intermediate stages were found between glycogenotic tubules, which in some cases may occur as early as 3 weeks after withdrawal of the carcinogen, and the clear or acidophilic cell tumors. The tubular glycogenosis is, therefore, taken to be a preneoplastic lesion. In addition to the characteristic clear cells, the tumors contained predominantly cells which stored lipids or which were rich in mitochondria. The fine structure of the tumors points to differentiated renal tubules as the tissue of tumor origin. The glycogen of the clear cells is located preferentially in the ground cytoplasm, but it may also be enclosed in autophagic vacuoles. The lipids form membranous cytoplasmic bodies (MCB) with a regular pattern of dark and light lines (periodicity 5–7 nm). The mitochondria of the tumor cells, especially those of the acidophilic cells, were often characterized by a severe reduction of their cristae. Sometimes large mitochondria poor in cristae but rich in matrix were found. Interstitial cells rich in acid mucopolysaccharides were loosely distributed throughout the clear cell tumors. We suggest that the cellular thesaurismoses (glycogenosis, lipidosis, mucopolysaccharidosis) indicate a disturbance of cell metabolism, which might be closely correlated with the process of carcinogenesis.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 92 (1978), S. 87-104 
    ISSN: 1432-1335
    Keywords: Oncocytes ; Mitochondria ; Intramitochondrial glycogen ; Intercristal cross bridges ; Interstitial cells ; Onkocyten ; Mitochondrien ; intramitochondriales Glykogen ; Intercristale Querbrücken ; Interstitielle Zellen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Genese von Nierenonkocytomen wurde in Stoppversuchen an 218 Nitrosomorpholin-vergifteten und an 69 unbehandelten Ratten stufenweise licht und elektronenmikroskopisch verfolgt. Am Ende der 3–14 wöchigen Vergiftungsphase sind in den Nieren der Versuchsratten morphologisch keine Unterschiede gegenüber den Kontrollen festzustellen. Mehrere Wochen nach Absetzen des Carcinogens kommt es jedoch — neben anderen Tubulusläsionen — häufig zu einer onkocytären Transformation von Tubulusepithelien. Onkocytäre und distale Tubulusabschnitte gehen oft unvermittelt ineinander über. Nach einer Latenzzeit von 22–97 Wochen zeigen die Nieren von 66% der Versuchstiere Onkocytentubuli. Ausgehend von diesen Tubuli entwickeln sich während des gleichen Zeitraumes bei 36% der Versuchstiere onkocytäre Mikroadenome. Von den gleichaltrigen Kontrollratten zeigen ca. 20% einzelne Onkocytentubuli und 6% onkocytäre Mikroadenome. In manchen Nierentubuli der Versuchstiere sind die Onkocyten mit Glykogenoder Lipidspeicherzellen kombiniert. Im Cytoplasma der Onkocyten sind ungewöhnlich cristareiche Mitochondrien mit verschiedenartigen strukturellen Anomalien angehäuft. In einzelnen Mitochondrien sind die Cristae streng parallel geordnet und durch 15–20 nm breite Querbrücken miteinander verbunden. Mitunter treten intramitochondriale Glykogenaggregate auf, die von einer einfachen Membran begrenzt sind. Neben den Mitochondrien finden sich nur wenige andere Cytoplasmakomponenten, wie z.B. einzelne Vesikel des ER, Golgikomplexe oder Lipidkörper mit einem regelmäßigen Linienmuster (Periodik 3–4 nm). In manchen Onkocyten sind reichlich β-Glykogenpartikel in die cytoplasmatische Matrix eingelagert. Einzelne Onkocyten zeigen eine homogene Verdichtung von Kern und Cytoplasma. Zwischen die Onkocyten sind häufig mucopolysaccharidspeichernde interstitielle Zellen eingelassen. Es wird vermutet, daß der Onkocyt eine besondere Form einer neoplastisch transformierten Zelle ist.
    Notes: Summary The development of renal oncocytomas was followed by light and electron microscopy in rats treated with N-nitrosomorpholine for a limited time (stop experiment). At the end of the period of treatment (3–14 weeks) the kidneys of the experimental animals were morphologically unchanged as compared with the controls. However, some weeks after cessation of the carcinogenic treatment an oncocytic transformation of tubular epithelia frequently occurred, in addition to other tubular lesions. Distal and oncocytic tubular segments are often directly connected. Oncocytic tubules were present in 66% of the experimental animals after a lag period of 22–97 weeks. Oncocytic microadenomas originated from these tubules, and developed in 36% of the experimental animals during the same period. Of 45 control rats of the same age, about 20% showed single oncocytic tubules, while 6% had oncocytic microadenomas. In some renal tubules the oncocytes were found in combination with cells which stored excessive amounts of glycogen or lipids. Unusual mitochondria accumulated in the cytoplasm of the oncocytes. These were rich in cristae, and showed diverse structural anomalies. In some mitochondria the cristae were aligned in a strictly parallel fashion and were connected by cross bridges 15–20 nm broad. Sometimes intramitochondrial aggregates of glycogen appeared which were surrounded by a single membrane. Only a few other cytoplasmic components were seen in addition to mitochondria; these included ER-vesicles, Golgi complexes or lipid bodies with a regular pattern of dark and light lines (periodicity: 3–4 nm). Numerous β-glycogen particles were found in the cytoplasmic matrix of some oncocytes. A few oncocytes showed a homogeneous condensation of the nucleus and the cytoplasm. Interstitial cells rich in mucopolysaccharides were often found in between the oncocytes. We suggest that the oncocyte is a special type of neoplastically transformed cell.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 115 (1989), S. 329-334 
    ISSN: 1432-1335
    Keywords: Preneoplastic liver foci ; Extrafocal hepatic tissue ; Liver cell tumors ; [3H]thymidine-labelling index
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sequential changes in cell proliferation and cellular phenotype during hepatocarcinogenesis induced in rats with N-nitrosomorpholine were investigated by autoradiographic determination of the [3H]thymidine-labelling index in morphologically defined focal lesions and extrafocal hepatic tissue at different times between 4 and 48 weeks after withdrawal of the carcinogen (stop model). The labelling index was found to be significantly increased in all types of preneoplastic and neoplastic hepatic lesions as compared to both the liver tissue of untreated controls and the extrafocal parenchyma of N-nitrosomorpholinetreated rats. However, the extent of the increase in labelling index differed in the phenotypically diverse types of preneoplastic and neoplastic lesions. There was a significant but relatively small increase in the labelling index in clear and acidophilic cell foci. A much stronger elevation of cell proliferation was characteristic of mixed and basophilic cell foci. The development of hepatocellular adenomas and carcinomas from preneoplastic hepatic foci was further characterized by an additional increase in cell proliferation. Each specific cellular phenotype was associated with a rather uniform proliferation rate, which remained elevated at all time points studied, suggesting that the rate of cell proliferation in the phenotypically diverse preneoplastic hepatic foci mainly reflects the intrinsic growth potential of the respective cellular phenotypes. The results support the concept that the predominant sequence of cellular changes in hepatocarcinogenesis induced by the stop model leads from the clear and acidophilic cell foci, storing glycogen in excess, through mixed and basophilic cell foci to hepatocellular adenomas and carcinomas. The fact that the labelling index of the extrafocal liver tissue of N-nitrosomorpholine-treated rats was also significantly higher than that of the normal parenchyma of untreated controls might indicate an involvement of extrafocal hepatocytes, in addition to that of foci of altered hepatocytes, in hepatocarcinogenesis.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-2307
    Keywords: Key words Renal cell carcinomas ; Preneoplastic lesions ; Mucin ; Thomsen-Friedenreich-related antigens ; Cytokeratin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The expression of MUC1, MUC2, mucin-associated Thomsen-Friedenreich-related antigens (TF, sialosyl-TF, Tn, and sialosyl-Tn), and cytokeratin 19 (CK19) was systematically investigated in situ in 58 resected human kidney tumours, surrounding tissue of normal appearance, and two normal kidneys obtained at autopsy, using monoclonal antibodies. In kidney tissues of normal appearance, TF, s-TF, MUC1 and CK19 were positive in distal tubules and collecting ducts but negative in proximal tubules. In contrast, MUC2, Tn, and s-Tn were negative throughout the normal renal tubular system. Almost all renal cell carcinomas (RCCs) showed strong immunoreactivity for MUC1, but all were negative for MUC2. Some RCCs expressed TF, Tn, s-Tn, and CK19. In addition, the immunomorphological characteristics of the majority of clear-cell RCCs and clear/granular RCCs with anti-MUC1 and anti-CK 19 closely resembled those of the collecting duct and the distal tubule rather than the proximal tubule. In the renal tissue of otherwise normal appearance adjacent to clear-cell RCCs and clear/granular RCCs, clear cells with excessive storage of glycogen were often found in the collecting duct system, but only rarely in the proximal tubules. These results suggest that the majority of clear-cell RCCs and clear/granular RCCs may originate from the collecting duct system.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 98 (1980), S. 243-265 
    ISSN: 1432-1335
    Keywords: Chromophobic tubules ; Basophilic tubules ; Polysaccharides ; Microbodies ; Brush borders ; Mitochondrial anomalies ; Chromophobe Tubuli ; basophile Tubuli ; Polysaccharide ; Mikrokörper ; Bürstensaum ; Mitochondrienanomalien
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Genese basophilzelliger Nierenepitheliome wurde in Stoppversuchen an N-Nitrosomorpholin-vergifteten Ratten stufenweise licht-und elektronenmikroskopisch verfolgt. Sieben Wochen nach Beginn der Giftzufuhr traten erstmals ungewöhnlich großzellige “chromophobe” oder basophile Tubuli auf. Sie waren zunächst nur bei einzelnen, nach einer Latenzzeit von 22–97 Wochen aber bei über 60% der Versuchstiere zu finden. Während des gleichen Zeitraumes entwickelten sich bei nahezu 50% der Carcinogen-vergifteten Ratten basophilzellige Nierenepitheliome. Morphologische Befunde, die als Übergänge von chromophoben oder basophilen Tubuli in Tumoren gedeutet werden können, waren häufig zu erheben. In der Regel wurden die chromophoben Epithelien offenbar schon früh im Verlaufe der neoplastischen Transformation in basophile Zellen umgewandelt. Ein Teil der chromophoben Nephronabschnitte sowie zahlreiche Tubuli, die aus einer Mischung von chromophoben und basophilen Epithelien zusammengesetzt waren, speicherten nach Ausweis histochemischer Reaktionen saure Mucopolysaccharide. Die Feinstruktur der meisten basophilen Epitheliome war sehr einheitlich. Elektronenmikroskopisches Äquivalent der lichtmikroskopisch beobachteten cytoplasmatischen Basophilie war ein großer Ribosomenreichtum. Bürstensaumstrukturen und Mikrokörper belegten die Abstammung der basophilen Nierentumoren vom proximalen Nephron. Gelegentlich fanden sich auffallend mitochondrienreiche Tumorzellen, die Onkozyten ähnelten. Im Gegensatz zu typischen Onkozyten zeichneten sich die Mitochondrien dieser Zellen entweder durch eine Cristaarmut oder durch eine tubuläre Transformation der Innenmembranen aus. In manchen Mitochondrien waren eigenartige Cristae zu beobachten, die durch eine homogene Verdichtung des intracristalen Spaltraumes sowie durch die Ausbildung von Zacken an der Cristaoberfläche auffielen. Das Schnittbild derartiger Cristae ähnelte einem Sägeblatt. Akute Tubulusläsionen und intratubuläre Zellregenerate, wie sie von zahlreichen Autoren als Frühstadien der Tumorbildung in der Niere beschrieben wurden, haben wir nicht beobachtet. Wir nehmen an, daß die in zahlreichen Tubuli und in einigen Tumoren nachweisbare Speicherung von sauren Mucopolysacchariden eine zelluläre Stoffwechselstörung anzeigt, die eine wichtige Rolle bei der Geschwulstbildung spielt.
    Notes: Summary The genesis of basophilic cell kidney tumors was investigated stepwise by light and electron microscopy in rats treated with N-nitrosomorpholine for a limited time (stop experiment). Seven weeks after the beginning of the experiment the kidney tubules sometimes showed unusually large “chromophobic” and basophilic cells. After a lag period of 22–97 weeks more than 60% of the animals had developed these atypical tubules. Parallel to the appearance of chromophobic tubules 50% of the carcinogen-treated animals developed basophilic cell kidney tumors. All intermediate stages between chromophobic or basophilic cell tubules and tumors were found. During the neoplastic transformation chromophobic epithelia appeared to change into basophilic cells. Some of the chromophobic renal tubules and most of the renal tubules which consisted of chromophobic and basophilic epithelia stored acid mucopolysaccharides as demonstrated by histochemical methods. The fine structure of the basophilic epitheliomas was relatively uniform. The basophilia observed under the light microscope correlated with abundant membrane-bound and free ribosomes as seen under the electron microscope. The frequent appearance of brush borders and microbodies indicated the origin of the basophilic cell tumors from proximal renal tubules. In some tumor cells many mitochondria were found. These cells resembled oncocytes. However, in contrast to typical oncocytes the mitochondria of these cells were poor in cristae or showed tubular formations of the inner membrane. In some mitochondria homogeneous condensations could be detected in the intracristal space and tooth-like formations were seen on the surface of the cristae. In perpendicular sections these cristae resembled saw blades. Acute tubular lesions and cellular regeneration, as described earlier by other authors in early stages of the development of kidney tumors, were not found. It is suggested that the storage of acid mucopolysaccharides observed in many tubules and in some renal tumors indicates adisturbance of the cellular metabolism which plays an important role in tumor development.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular histology 13 (1981), S. 799-820 
    ISSN: 1573-6865
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Conclusions While the understanding of early cellular changes gleaned from conventional histopathology alone has been rather limited, modern cytochemical methods at the light and electron microscope level have revealed in a number of experimental models and in some human tumour types important results which indicate that a sequence of qualitatively different cell populations is followed during carcinogenesis Some of the cytochemical and electron microscope findings can be correlated with specific cytopathological phenomena which are readily detectable in routine H & E sections. Thus the evaluation of animal experiments concerned with the testing of chemical compounds for carcinogenicity has been improved. The use of simple cytochemical techniques may considerably increase the reliability of the results. With respect to the further elucidation of the mechanism of neoplastic cell transformation, cytochemistry has broadened research horizons. The identification of putative preneoplastic and early neoplastic cell populations by cytochemical methods allows for the first time the microdissection and subsequent detailed investigation of target cells of the carcinogen which are at a high risk of becoming cancer cells. The combination of cytochemical and biochemical microanalysis seems to be the most useful tool for clarifying a number of important problems of carcinogenesis at present.
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