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  • 1
    Publication Date: 2020-03-27
    Language: English
    Type: article , doc-type:article
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Terra nova 9 (1997), S. 0 
    ISSN: 1365-3121
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Geosciences
    Notes: An integrated interpretation of seismicity, fault plane solutions and deep seismic reflection data suggests that the NE–SW to NW–SE trending Rhone–Simplon fault zone and the gently S-dipping basal Penninic thrust separate fundamentally different stress regimes in the western Swiss Alps. North of the Rhone-Simplon fault zone, strike-slip earthquakes on steep-dipping faults within the Helvetic nappes are a consequence of regional NW–SE compression and NE–SW extension. To the south, vertical maximum stress and N–S extension are responsible for normal mechanism earthquakes that occur entirely within the Penninic nappes above the basal Penninic thrust. Such normal faulting likely results from extension associated with southward movements (collapse) of the Penninic nappes and/or continued uplift and relative northward displacements of the underlying Alpine massifs. Geological mapping and fission-track dating suggest that the two distinct stress regimes have controlled tectonism in the western Swiss Alps since at least the Neogene.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 106 (1983), S. 17-20 
    ISSN: 1432-1335
    Keywords: Tumor stem-cell cloning ; Polyamines ; Polyamine oxidase ; Polyamine oxidase inhibitor ; Fetal calf serum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Several tumors are characterized by elevated levels of polyamines involved in vital cell proliferation processes. Polyamine oxidases (PAO), present in ruminant and particularily in fetal calf serum (FCS), degrade polyamines to polyaminoaldehydes and other products that inhibit cell proliferation. Since most in vitro assays for cloning tumor stem cells use FCS as an essential supplement of the nutrient media, we examined the effects of specifically inhibiting the PAO activity on the clonal growth of leukemic cells and the following normal lymphocytes: the W 25 rat chloroleukemia, the M1 mouse myeloblastic and the L 1210 rat lymphoblastic leukemia, a primary human acute myeloblastic leukemia (AML) and acute lymphocytic leukemia (ALL) as well as normal human PHA-stimulated lymphocytes. In the presence od horse serum, nontoxic doses of the PAO inhibitor 1-hydroxybenzyloxyamine did not affect colony growth of either cell type. However, in the presence of FCS, clonal growth of W 25, ALL, AML, and PHA lymphocytes was significantly stimulated by the enzyme inhibitor. Our data suggest (a) that poor cell proliferation of several tumors in vitro may result from the reaction of polyamines (from cells) and PAO (from serum), (b) that this can be easily tested by means of a specific PAO inhibitor, and (c) that the growth conditions can be optimized by adding nontoxic doses of the enzyme inhibitor or by exchanging FCS for another serum.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1335
    Keywords: Colorectal cancer ; LAK cell activity ; Prothymosin α1 ; Cytokines ; Adhesion molecules
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of prothymosin α1 (Pro α1) in combination with interleukin-2 (IL-2) on peripheral blood lymphocytes from 50 colorectal tumor patients at different stages were studied with respect to immunocytotoxicity, adhesion to cultured SW620 colon carcinoma cells, secretion of cytokines and expression of adhesion and surface marker molecules. On average, the patients showed lower natural killer (NK) cell activity than healthy donors, which was associated with a lower adhesion capacity to the tumor target cells. The NK cell activity of the patients was inversely related to the tumor stage. The generation of lymphokine(IL-2)-activated killer (LAK) cell activity was found to be comparable on lymphocytes from healthy individuals and patients and was not correlated to tumor stage. Pro α1 stimulated patients' LAK cell activity only, primarily at the early stage (Dukes A/B). The Pro α1 effect was associated with an increased adhesion of lymphocytes to tumor target cells and an increased secretion of the deficient IL-2-induced IFNγ secretion. No significant effects on the low level of TNFα secretion was noted. By flow cytometry, Pro α1 in combination with IL-2 augmented the expression of the NK cell markers CD56, CD16/56, the subset CD3/16/56 and CD25 on lymphocytes of the patients. In contrast, Pro α1 was equally effective by increasing the expression of CD18 and CD11a, on lymphocytes from the patients and from normal controls. In conclusion, Pro α1, in combination with IL-2, can partially normalize lymphocyte deficiencies of colon cancer patients in vitro. This potential might provide an experimental basis for applying Pro α1 or related thymic peptides in selected immunotherapies against colorectal tumors.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 95 (1979), S. 129-138 
    ISSN: 1432-1335
    Keywords: Methylhydrazones ; 3H-Thymidine uptake ; Colony growth of granulocytes and lymphocytes ; Methylhydrazone ; 3H-Thymidin-Aufnahme ; Granulocytenund Lymphocyten-Kolonie-Wachstum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die cytostatischen und immunsuppressiven N′-Methyl-N′-β-chloräthylbenzaldehydhydrazone B1 und B2 hemmen dosisabhängig das Kolonie-Wachstum von Mäuse-Knochenmarkzellen und PHA-stimulierten, humanen Lymphocyten in vitro. Im Gegensatz zu B2 jedoch hemmt B1 die 3H-Thymidin-(3H-Tdr)-Aufnahme in die Knochenmarkzellen und Lymphocyten nur wenig. Zwei weitere Benzaldehydhydrazone CyB4 und EB4 beeinflussen sowohl das Kolonie-Wachstum als auch die Nukleosid-Aufnahme nur geringfügig bzw. gar nicht. Im 3H-Tdr-Assay bei ConA-bzw. LPS-stimulierten Mäusemilz-Zellen jedoch hemmt CyB4 stärker die Nukleosid-Aufnahme als B1 und B2, obwohl es im Gegensatz zu B1 und B2 in vivo bei der Maus keine immunsuppressive Wirkung besitzt. Die Untersuchungen zeigen, daß die 3H-Tdr-Methode weniger empfindlich als die Kolonie-Methoden ist und somit nur beschränkt als Maß für die In-vitro-Proliferation von Cytostatica-behandelten Säugetier-Zellen angewandt werden kann.
    Notes: Summary The cytostatic and immunosuppressive N′-methyl-N′-β-chloroethylbenzaldehyde hydrazones B1 and B2 inhibit the colony growth of mouse bone marrow cells and PHA-stimulated human lymphocytes in vitro in a dose-dependent manner. In the presence of B1, however, in contrast to B2, the inhibition of 3H-thymidine (3H-Tdr) uptake by the bone marrow cells and lymphocytes is insignificant. Two further benzaldehydrazones CyB4 and EB4 show little or no influence both on colony growth and nucleoside uptake. On the other hand, CyB4 inhibits the 3H-Tdr uptake by ConA- or LPS-stimulated mouse spleen cells to a greater degree than does B1 or B2, although CyB4 unlike B1 or B2 does not display any immunosuppressive effects in the mouse. These findings demonstrate that the 3H-Tdr method is less sensitive than the colony assays and is hence only of limited value as a measure of the vitro proliferation of mammalian cells treated with cytostatics.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0738
    Keywords: Valepotriates ; Epichlorohydrin ; Scopolamine ; Granulocyte/Macrophage ; Erythrocyte ; T-Lymphocyte colony assays
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die epoxidhaltigen Valepotriate Valtrat/Isovaltrat und Dihydrovaltrat, die aus den Wurzeln von Valerianaceae isoliert und als sedative Arzneimittel benutzt werden, wurden hinsichtlich ihrer Wirkung auf untransformierte hämatopoietische Zellen untersucht, nachdem ein Alkylierungspotential und Zytotoxizität auf Tumorzellen gefunden worden waren. Die Stoffe wurden in empfindlichen in vitro-Tests bezüglich ihrer Wirkung auf Vorläuferzellen für Granulo/yten/Makrophagen (GM-CFC) und Erythrozyten (E-CFC) aus dem Knochenmark von Mäusen sowie auf Kolonie-bildende PHA-stimulierte T-Lymphozyten des menschlichen peripheren Blutes geprüft. Bei Valtrat-Zugabe betrug die ID50 für GM-CFC und T-Lymphozyten ca. 3×10−6 M, bei Dihydrovaltrat ca. 2×10−5 M. Für E-CFC-Kolonien ergab sich bei beiden Substanzen eine ID50 von ca. 3×10−8 M. Die Wirkung von Valtrat zeigte sich bei niedrigerer Konzentration als die Wirkung des bekannten Alkylans Epichlorhydrin. Das zum Vergleich untersuchte nichtalkylierende Epoxid l-Scopolamin war eindeutig am wenigsten wirksam. Die Valtrat- und Dihydrovaltrat-Effekte waren nicht reversibel durch Auswaschen der Kulturen. Es kann geschlossen werden, daß die untersuchten Valepotriate wahrscheinlich stark zytotoxisch sind für die in den Tests verwendeten untransformierten hämatopoietischen Zellen.
    Notes: Abstract The epoxide-bearing valepotriates valtrate/isovaltrate and dihydrovaltrate, isolated from Valerianaceae roots and used as common sedative drugs, were investigated for their effects on untransformed hematopoietic cells after an alkylating potential and cytotoxicity to tumor cells had been found. The compounds were added to sensitive in vitro assays using granulocyte/macrophage (GM-CFC) and erythrocyte (E-CFC) colony forming cells from murine bone marrow early progenitor cells as well as colony forming PHA-stimulated T-lymphocytes from human peripheral blood. The ID50 for both GM-CFC and T-lymphocytes incubated with valtrate was found to be about 3×10−6 M, with dihydrovaltrate about 2×10−6 M. On erythrocyte colonies (E-CFC) both compounds showed an ID50 of about 3×10−8 M. Valtrate effects were exhibited at lower concentrations than effects caused by the known alkylating agent epichlorohydrin. The non-alkylating epoxide l-scopolamine taken for reference was clearly the least effective. Valtrate and dihydrovaltrate effects on GM-CFC were not reversible by washing the cultures. It is concluded that the valepotriates investigated are likely to be strongly cytotoxic to the untransformed hematopoietic cells studied.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 98 (1980), S. 221-231 
    ISSN: 1432-1335
    Keywords: L 1210 ; Cell growth kinetics ; 3H-thymidine uptake ; Suspension culture ; Agar culture ; Normal lymphocytes ; Cytostatic agents ; L 1210-Zellen ; normale Lymphocyten ; Zellwachstumskinetik ; 3H-Thymidine-Aufnahme ; Suspensionskultur ; Agarkultur ; Cytostatika
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Folgende drei Methoden zur Messung von Zellproliferation wurden mittels wachstumskinetischer Studien an L 1210-Zellen verglichen: Zelluläre 3H-Tdr-Aufnahme, Bestimmung der Zelldichte von Suspensionskulturen und Koloniezählung in Agar-haltigen Glaskapillaren. Die Agar-kultur-Methode erwies sich als die geeignetste und methodisch vorteilhafteste. Unter Anwendung dieser drei cytokinetischen Modelle untersuchten wir die unterschiedlichen Empfindlichkeiten von exponentiell und stationär wachsenden L 1210-Zellen und normalen, PHA-stimulierten, menschlichen T-Lymphocyten auf MTX, Ara-C, Aza und ein teilweise gereinigtes Lymphocyten-Chalon. Die L 1210-Zellen der exponentiellen Phase zeigten höhere Empfindlichkeiten auf die Agenzien als die der stationären Phase. Normale menschliche T-Lymphocyten waren im Vergleich dazu weniger empfindlich. Für die Bestimmung der unterschiedlichen Empfindlichkeiten der Zellen war die Agarkultur-Methode doppelt so empfindlich wie Zellzählung von Zellsuspensionen und bis zu achtfach empfindlicher als die Messung der 3H-Tdr-Aufnahme.
    Notes: Summary Three methods of measuring cell proliferation, viz., cellular 3H-thymidine uptake, counting of cells in suspension, and counting of colonies of cells grown in agar contained in glass capillaries, were compared by studying cell growth kinetics using the L 1210 cell line. We found the agar colony culture method to be most suitable and methodologically most advantageous. Using these cytokinetic models, we investigated the differential sensitivities of exponential and stationary phase L 1210 cells and normal, human, PHA-stimulated, peripheral T-lymphocytes to methotrexate, cytosine arabinoside, azathioprine, and a partially purified lymphocyte chalone preparation. L 1210 cells in exponential growth showed a higher drug sensitivity to all the agents tested than those in stationary growth. Normal, human T-lymphocytes exhibited less sensitivity to the tested agents. We found the agar culture to be more than twice as sensitive as the suspension culture and up to 8-fold more sensitive than the 3H-thymidine uptake method.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0584
    Keywords: Thymocytes ; Colony formation ; Agar gel ; Glass capillaries ; Il-2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Optimal growth conditions are presented for a new colony test with mouse thymocytes in agar contained in glass capillaries. The kinetics of colony growth and the dependence from the PHA-, Il-2-, agar- and 2-mercaptoethanol concentration are shown. The colony forming cells are identified as T-lymphocytes by usual morphology and by an indirect immunoperoxidase method using mouse anti-Thy 1.2 antibodies.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Annals of hematology 59 (1989), S. 171-176 
    ISSN: 1432-0584
    Keywords: Serum-free cultures ; Granulocyte-Macrophage colonies ; Agar gel ; Glass capillaries
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Culture conditions were determined and optimised for the serum-free growth of granulocyte-macrophage (GM) colonies, derived from mouse bone marrow cells, in agar-containing glass capillaries. The standard medium is DMEM/F-12 (1:1) mixture containing per ml: 10 mg BSA, 35 μg transferrin, 20 μg soybean lipids and 5 μg insulin. In contrast to previous attempts by others, GM-colony yield in serum-free medium was found to be equal to that in serum-containing medium (around 25 colonies/capillary) and to correlate satisfactorily with the cell density at seeding. — The role of polyamine oxidases in cell-proliferation experiments could be studied by this microclonogenic assay without interference from any type of serum.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0584
    Keywords: Mafosfamid effects ; LAK cells ; Clonogenic microassay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of mafosfamid on lymphokine-activated killer (LAK) cells were examined, using a newly developed clonogenic microassay with tumor target cells instead of the common51Cr release. When nonadherent peripheral blood mononuclear effector cells were exposed to 1×10−9 or 1×108 M mafosfamid 1 h prior to activation with interleukin 2 (IL-2), LAK-cell activity increased, resulting in fewer colonies of human KB squamous carcinoma cells than without mafosfamid treatment. In contrast, when effector cells were exposed to mafosfamid after IL-2 activation LAK-cell activity was inhibited. Notably, the in vitro immunomodulatory effects of mafosfamid were detected at concentrations 100–1000 times below those shown to be cytotoxic. Although the mechanisms remain to be elucidated, our results might be an in vitro representation of the known in vivo immunostimulation of low doses of cyclophosphamide.
    Type of Medium: Electronic Resource
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