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  • 1
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The status of T-cell receptor beta and gamma genes has been assessed in a series of primary tumors induced by a chemical carcinogen or by gamma-irradiation using two inbred strains of mice. It appears that these well-characterized regimens of carcinogenesis yield T-cell tumors showing gene rearrangements consistent with a clonal origin of the tumors. Individual rearranged bands seem to represent orthodox, intralocus recombination events. A variety of rearrangement phenotypes are observed, most strikingly for the gamma genes, and differences in the degree of T-cell receptor gene rearrangements observed can be categorized according to the inducing agent and to the genetic background of the mice, with the implication that premalignant thymocytes have been captured in different stages of T-cell development. Additionally, primary tumors were shown to express significant levels of mature beta gene mRNA.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Immunogenetics 38 (1993), S. 300-303 
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
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  • 3
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Ras proteins regulate cellular growth and differentiation, and are mutated in 30% of cancers. We have shown recently that Ras is activated on and transmits signals from the Golgi apparatus as well as the plasma membrane but the mechanism of compartmentalized signalling was not determined. Here ...
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  • 4
    ISSN: 1546-1696
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: [Auszug] Successful cancer gene therapy requires a vector that systemically and specifically targets tumor cells throughout the body. Although several vectors have been developed to express cytotoxic genes via tumor-specific promoters or to seclectively replicate in tumor cells, most are taken up and ...
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Somatic cell and molecular genetics 12 (1986), S. 1-12 
    ISSN: 1572-9931
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We cotransformed mouse 3T3 cells with total genomic human DNA and the dominant selectable bacterial gene Neoand analyzed 121 NeoR clones for expression of 15 human “housekeeping” enzymes which can be distinguished from their murine homologs. The estimated frequency of expression of unlinked human genes was 1 in 360 NeoR clones and at least three different human enzymes (peptidase D, phosphoglucomutase 1, and acid alpha glucosidase) were detected. We further examined the frequency and stability of cotransformation for one of these enzymes, acid alpha glucosidase (GAA). We tested approximately 4000 NeoR clones and found 25 clones expressing human GAA, as determined by rocket immuno-electrophoresis (RIE) specific for human GAA. Transformants progressively became negative on continued growth and retesting by RIE, with only two clones still expressing GAA at the eighth testing. This apparent loss of expression was not due to nonclonality of the original isolates. In one subclone examined, loss of expression was accompanied by loss of both Neo -derived pBR322 and human Alu repetitive sequence DNA. Thus, under the conditions utilized, cotransformants expressing homomeric housekeeping enzymes were found at relatively high frequency but were progressively lost even under conditions selective for expression of the dominant vector.
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  • 6
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 141 (1989), S. 60-64 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Quantification of changes in levels of c-fos RNA was used as an indicator of the presence of functional responses to nerve growth factor in several human nonneuronal cell lines which have previously been shown to express high levels of NGF receptors. Four Ewing's sarcomas, one Wilm's tumor, and one melanoma were examined. Of these cell lines, the Ewing's sarcoma IARC-EW1 showed greatly increased levels (10-20-fold) of c-fos RNA after 1 hour of exposure to NGF. Except for the melanoma line, the other tumor lines exhibited small, but reproducible, elevation of c-fos RNA expression. In IARC-EW1 cells, this induction was analyzed for kinetics, dose-response, and suppression by selective inhibitors of NGF action. The results indicate that these cells bear high-affinity receptors for NGF, which utilize signal pathways similar to NGF receptors on PC12 cells. Thus, we report new types of cells with functional responses to NGF and indicate that these may constitute a new model which will usefully complement those presently used for studying the mechanism of action of NGF.
    Additional Material: 5 Ill.
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  • 7
    ISSN: 1432-1777
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Genetic distance measures between the laboratory mouse strains C57BL/6J and RF/J and the wild-origin Mus musculus mouse strains CAST/Ei, MOLF/Ei, POSCH I, and CZECH II were estimated by allelic patterns revealed by RFLP analysis. These results suggest phylogenetic relationships indicating that the mouse strains related to the subspecies M.m. domesticus (RF/J, POSCH I and C57BL/6J) are more closely related to the CAST/Ei strain (derived from M.m. castaneus) than to the strains CZECH II (M.m. musculus) and MOLF/Ei (M.m. molossinus). Furthermore, the hybrid strain C57BL/6J is more closely related to POSCH I (M.m. poschiavinus) than to RF/J as calculated by the method distance measures of Cavalli-Sforza and Edwards (Evolution 21,550, 1967), Nei's minimum (Am. Natural. 106,283, 1972) and unbiased minimum (Genetics 89,583, 1978), Edwards (Biometrics 27,873, 1971; Genetic Distance, p. 41, 1974) and Rogers modified (1986).
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  • 8
    ISSN: 1432-1777
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. The cyclin-dependent kinase inhibitors p15 INK4b and p16 INK4a are involved in the development of a wide range of human and murine tumors. These tumor suppressor genes are inactivated by deletions frequently associated to point mutations in the coding regions or hypermethylation of their promoters. In this work, we describe a simple-sequence length polymorphism located in mouse Chromosome (Chr) 4, between the Cdkn2B (p15 INK4b ) and Cdkn2A (p16 INK4a ) genes, only 700 bp downstream of the Cdkn2B locus. This DNA region was analyzed in different inbred strains showing a variable AC-repetitive DNA sequence. We used this microsatellite to detect loss of heterozygosity of the Cdkn2A and Cdkn2B loci in γ-irradiation-induced thymic lymphomas of C57BL/6J × RF/J F1 hybrids. Using this specific marker, we were able to locate additional allelic losses not detected by other microsatellites. Since the allelic losses can be detected by a simple PCR amplification, this AC-repetitive sequence is specially useful as a genetic marker for these Cdkn2 genes and specifically for the p15 INK4b cell cycle inhibitor.
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  • 9
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: A recombinant N-ras oncogene, under the transcriptional control of a corticosteroid-inducible mouse mammary tumor virus (MMTV) promoter, has been stably transfected into a PC12 rat pheochromocytoma subline. This cell line, designated UR61, undergoes N-ras-induced neurite outgrowth and cessation of division when treated with dexamethasone (Guerrero et al.: Biochemical and Biophysical Research Communications 150:1185-1192, 1988). We have employed the UR61 cell line as a model for ras oncogene-induced neuronal differentiation. In UR61 cells, dexamethasone-induced expression of the recombinant N-ras gene resulted in time-dependent expression of ornithine decarboxylase enzyme (ODC) activity. Prompted by recent reports of possible functional (Lacal et al.: Molecular and Cellular Biology 7:4146-4149, 1987; Wolfman and Macara: Nature 325: 359-361, 1987) and direct (Jeng et al.: Biochemical and Biophysical Research Communications 145:782-788, 1987) interactions between oncogene ras-coded p21 and protein kinase C (PK-C; Ca+ +/phospholipid-dependent protein kinase), we employed the protein kinase inhibitor H-8 (N-[2-(methylamino)ethyl]-5-isoquinoline sulfonamide dihydrochloride) and phorbol 12, 13-dibutyrate (PDBu) to investigate this putative interaction in the UR61 cells, where ODC activity and neurite outgrowth were used as indicators of oncogenic N-ras action. Treatment of UR61 cells with PDBu depleted cells of PK-C and failed to promote neurite outgrowth but enhanced N-ras-induced neurite outgrowth and ODC activity. H-8, which suppressed ODC induction by forskolin and phorbol myristate acetate, enhanced both N-ras-induced ODC activity and neurite outgrowth. Inhibition of ODC activity by difluoromethylornithine (DFMO) did not suppress oncogenic ras-induced neurite outgrowth, suggesting that these two ras-triggered events are mechanistically independent. These findings suggest that certain actions of N-ras can occur in cells depleted of PK-C, and thus, the role of PK-C in ras-induced differentiation differs from its role in ras-induced mitogenesis and transformation.
    Additional Material: 6 Ill.
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  • 10
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 129 (1986), S. 71-76 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Activated mouse N-ras gene transfected into PC12 rat pheochromocytoma cells suppressed proliferation and promoted neuronal differentiation. Normal mouse N-ras in a LTR-containing vector caused differentiation with a reduced efficiency, but normal N-ras in a vector lacking LTR sequences failed to alter the PC12 phenotype. Cultures of NGF-resistant PC12 variant subline U7 also showed outgrowth of neurites and cessation of cell division following transfection with the mutated ras gene. The present findings suggest that ras genes can, in certain cells, play a role in promoting differentiation and suppressing proliferation, in contrast to their established oncogenic neoplasiapromoting activity in other cells.
    Additional Material: 3 Ill.
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