Muscle atrophy following section of the spinal cord in the rat

Zusammenfassung Nach Myelotomie verläuft die Muskelatrophie in zwei Phasen. In der ersten Phase stimmt der Gewichtsverlust der Muskeln mit demjenigen nach Denervation überein. Dagegen erfolgt in der zweiten eine Gewichtszunahme, die durch die analoge Gesamtzunahme des Körper-gewichts erklärt wird.     

Observations of a certain arrangement in the nucleolar chromatin after continuous ethidium bromide treatment

Summary This work is an ultrastructural and cytochemical study of a structure observed in the nucleolus of Allium cepa meristematic cells after nucleolar disgregation, by a continuous treatment of 12 h with ethidium bromide. The ultrastructural and cytochemical data allow us to consider this structure as the intranucleolar chromatin collapsed by the effect of the drug.     

Isolation of homogentisic acid from urine of alcaptonuric cases by means of an anion-exchanger

Zusammenfassung Die Homogentisinsäure liess sich aus alkaptonurischem Harn selektiv am schwach basischen Anionenaustauscher Anex adsorbieren. Nach der Elution mit Hilfe von 5M Essigsäure betrug die Ausbeute 60%. Die Methode ist auch im präparativen Ausmass gut durchführbar.     

Stress response of leucocytes in hypothyroid rats

Zusammenfassung Nach Formalininjektion zeigen mit getrockneter Schilddrüse gefütterte Ratten eine Abweichung der peripheren Leukocytenreaktion. Bei so behandelten Ratten mit Schilddrüsenhypofunktion ist die Vermehrung der Neutrophilen, die Lymphocytose und die Eosinophilie gehemmt. Auch die histologische Kontrolle ergab eine Hemmung der transitorischen Aktivitätssteigerung des lymphoretikulären Milzgewebes.     

Autophagy: molecular mechanisms,physiological functions and relevance in human pathology

Autophagy is a degradative mechanism mainly involved in the recycling and turnover of cytoplasmic constituents from eukaryotic cells. Over the last years, yeast genetic screens have considerably increased our knowledge about the molecular mechanisms of autophagy, and a number of genes involved in fundamental steps of the autophagic pathway have been identified. Most of these autophagy genes are present in higher eukaryotes indicating that this process has been evolutionarily conserved. In yeast, autophagy is mainly involved in adaptation to starvation, but in multicellular organisms this route has emerged as a multifunctional pathway involved in a variety of additional processes such as programmed cell death, removal of damaged organelles and development of different tissue-specific functions. Furthermore, autophagy is associated with a growing number of pathological conditions, including cancer, myopathies and neurodegenerative disorders. The physiological and pathological roles of autophagy, as well as the molecular mechanisms underlying this multifunctional pathway, are discussed in this review.Received 12 January 2004; received after revision 29 January 2004; accepted 4 February 2004     

Opposite roles of protein kinase C isoforms in proliferation, differentiation, apoptosis, and tumorigenicity of human HaCaT keratinocytes

We have previously shown that the protein kinase C (PKC) system plays a pivotal role in regulation of proliferation and differentiation of the human keratinocyte line HaCaT which is often used to assess processes of immortalization, transformation, and tumorigenesis in human skin. In this paper, using pharmacological and molecular biology approaches, we investigated the isoform-specific roles of certain PKC isoenzymes (conventional cPKC and ; novel nPKC and ) in the regulation of various keratinocyte functions. cPKC and nPKC stimulated cellular differentiation and increased susceptibility of cells to actions of inducers of apoptosis, and they markedly inhibited cellular proliferation and tumor growth in immunodeficient mice. In marked contrast, cPKC and nPKC increased both in vitro and in vivo growth of cells and inhibited differentiation and apoptosis. Our data present clear evidence for the specific, antagonistic roles of certain cPKC and nPKC isoforms in regulating the above processes in human HaCaT keratinocytes.Received 13 January 2004; received after revision 18 February 2004; accepted 25 February 2004     

Modulation of signal transduction through the cellular prion protein is linked to its incorporation in lipid rafts

Because expressed at a significant level at the membrane of human T cells, we made the hypothesis that the cellular prion protein (PrP^c) could behave as a receptor, and be responsible for signal transduction. PrP^c engagement by specific antibodies was observed to induce an increase in cytosolic calcium concentration and led to enhanced activity of Src protein tyrosine kinases. Antibodies to CD4 and CD59 did not influence calcium fluxes or signaling. The effect was maximal after the formation of a network involving avidin and biotinylated antibody to PrP^c and was inhibited after raft disruption. PrP^c localization was not restricted to rafts in resting cells but engagement was a prerequisite for signaling induction, with concomitant PrP^c recruitment into rafts. These results suggest a role for PrP^c in signaling pathways, and show that lateral redistribution of the protein into rafts is important for subsequent signal transduction.Received 22 July 2004; received after revision 10 September 2004; accepted 7 October 2004     

Increased apoptosis in differentiating p27-deficient mouse embryonic stem cells

In mouse embryonic stem (mES) cells, the expression of p27 is elevated when differentiation is induced. Using mES cells lacking p27 we tested the importance of p27 for the regulation of three critical cellular processes: proliferation, differentiation, and apoptosis. Although cell cycle distribution, DNA synthesis, and the activity of key G1/S-regulating cyclin-dependent kinases remained unaltered in p27-deficient ES cells during retinoic acid-induced differentiation, the amounts of cyclin D2 and D3 in such cells were much lower compared with normal mES cells. The onset of differentiation induces apoptosis in p27-deficient cells, the extent of which can be reduced by artificially increasing the level of cyclin D3. We suggest that the role of p27 in at least some differentiation pathways of mES cells is to prevent apoptosis, and that it is not involved in slowing cell cycle progression. We also propose that the pro-survival function of p27 is realized via regulation of metabolism of D-type cyclin(s).Received 25 February 2004; received after revision 5 April 2004; accepted 15 April 2004