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  • 1
    ISSN: 1432-1432
    Schlagwort(e): Lymphocytes ; B cells ; T cells ; Antigen P1 ; Topoisomerase
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary During the differentiation of the clonally distributed lymphocytes of mouse and man into mature resting B and T cells, their DNA becomes tightly packed into dense heterochromatin masses and exhibits very little transcriptional activity; it also becomes extensively nicked, containing some 3000–4000 single-strand breaks per diploid genome. The nuclear matrix is sparse and poorly organized and there are but trace amounts of the matrix-linked enzyme DNA topoisomerase II; the nucleus of these small cells is surrounded by a thin rim of cytoplasm. The resting cell can thus be considered (by analogy to a sperm cell) as a vector for transporting tightly packed and relatively inert genetic information to all parts of the body. When the lymphocyte is stimulated to enter a proliferative cycle by binding of appropriately presented antigen or mitogen to relevant membrane receptors, the cell enlarges, due to increased synthesis of protein; the dense heterochromatin is pulled out into very small clumps, as a result of an enormous growth in size as well as complexity of the nuclear matrix, and a great increase in transcriptional activity occurs. We have identified four nuclear matrix antigens that are very widely conserved in the evolution of eucaryotes and that occupy distinctive domains in interphase nuclei. Of particular interest is antigen P1, detected in organisms ranging from algae to mammals. By virtue of its location at the interface between nuclear envelope and chromatin, we propose that it plays a major and evolutionarily conserved role in chromatin organization and orientation in all eucaryotic cell types. Prior to these events, the DNA strand breaks are rejoined by a mechanism dependent on poly(ADP ribose) synthetase; rejoining of the breaks is required in order for the cells to enter the S phase of the cell cycle. Under certain experimental conditions, the induction of DNA topoisomerase II is clearly seen to precede DNA replication; topoisomerase II may be involved in some of the nuclear changes of blastogenesis. The evidence suggests that induction of single-strand breaks in DNA may be a general feature in the evolution of differentiated somatic cells. The selective advantage of the endogenously produced DNA strand breaks may be to provide an additional mechanism that prevents the differentiated cell from replicating its genome in the absence of an appropriate proliferative signal.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Chromosome research 4 (1996), S. 457-466 
    ISSN: 1573-6849
    Schlagwort(e): cell cycle ; HeLa ; immunolocalization ; lymphocytes ; Topo II isotypes
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract We have monitored the organization of DNA topoisomerase II (Topo II) in relation to chromatin disaggregation during mitogen stimulation of lymphocytes and to the mitotic chromosome condensation cycle by immunofluorescence microscopy with isozyme-specific antibodies. Labelling for both Topo IIα and Topo IIβ was diffusely nucleoplasmic and non-nucleolar in resting lymphocytes and the pattern changed little during stimulation. Topo IIα labelling intensity increased in parallel with the extent of cell stimulation, but a fraction of fully stimulated cells was labelled very brightly. Topo IIβ labelling intensity was also greater in stimulated cells, but all partially and fully stimulated cells were labelled at the same, higher, intensity. In addition, anti-Topo IIβ detected a few small spots within nucleoli of stimulated cells that coincided with regions containing fibrillarin. In lymphocytes and HeLa, chromosome association of Topo IIα began in prophase and lasted throughout mitosis. In contrast, Topo IIβ stayed nucleoplasmic in prophase, was diffusely cytoplasmic during mitosis, and was first detected post-mitotically in nuclel with decondensing chromosomes and a reformed nuclear envelope. The results are consistent with a role for Topo IIα, but not for Topo IIβ, in mitotic chromosome condensation, and indicate that the isotypes may play independent roles in the reorganization of chromatin structure during lymphocyte mitogenic activation.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    ISSN: 1434-9949
    Schlagwort(e): Immunological studies ; Rheumatoid arthritis ; Azathioprine ; Myocrisin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Thirty-one patients with classical or definite rheumatoid arthritis (RA), on treatment with azathioprine and sodium aurothiomalate in combination were studied. Absolute lymphocyte counts and IgA levels were reduced but this did not reach statistical significance. Lymphocyte transformation with phytohaemagglutinin (PHA) showed no significant difference from a control group. However, antibody dependent cell-mediated cytotoxicity was significantly impaired compared to rheumatoid controls (p〈0.001). There was no relation to the degree of impairment of ADCC and the current dose of azathioprine nor to the total dose or duration of therapy. Inhibiting material to cell-mediated cytotoxicity was present in the sera of 23 patients but its presence showed no relation to the degree of cytotoxicity exhibited by cells in the same patient. Our studies of cellular cytotoxicity have revealed alterations in cellular function possibly attributable to azathioprine.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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