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Biomedical subjects

C Muller

Publications and source records attributed to C Muller.

250 records · Page 14Linked to original sources

Regulation of the DNA-dependent protein kinase (DNA-PK) activity in eukaryotic cells.

The DNA-dependent protein kinase (DNA-PK) is a trimeric nuclear serine/threonine protein kinase consisting of a large catalytic sub-unit and the Ku heterodimer that regulates kinase activity by its association with DNA. DNA-PK is a major component of the DNA double strand break repair apparatus, and cells deficient in one of its component are hypersensitive to ionizing radiation. DNA-PK is also required to lymphoid V(D)J recombination and its absence confers in mice a severe combined immunodeficiency phenotype. The purpose of this review is to summarize the current knowledge on the mechanisms that contribute to regulate DNA-PK activity in vivo or in vitro and relates them to the role of DNA-PK in cellular functions. Finally, the studies devoted to drug-inhibition of DNA-PK in order to enhance cancer therapy by DNA-damaging agents are presented.

Animals↗

Cell membrane lipid fluidity and receptor expression in Moloney- and Friend virus-transformed cells.

Normal and malignant cells show differences in cell membrane lipid fluidity (CMF) which influence the expression of membrane receptors and may interfere with cell function. Friend virus (FLV) and Moloney virus (MLV) infected hematopoietic and lymphoid cells were monitored for CMF (fluorescence polarization) and for transferrin (TFC) and thymic (Thy) receptors (FITC-labelled monoclonal antibodies). CMF was modulated with cholesterol hemisuccinate (CHS), phospholipids (PL) and DMSO. Erythropoietic stem cells exhibit an increased persistent CMF within minutes after FLV infection; transferrin receptors are expressed, yet no hemoglobin is synthesized. CHS rigidification reduces TFC expression with differentiation of cells and hemoglobin synthesis, yet transformed cell populations do not react uniformly. Thymic lymphocytes, instead, do not exhibit changes in Thy expression upon CHS treatment although cell membranes become rigidified. Separate experiments showed these cells not being "transformed" per se but blocked in differentiation because of viral destruction of thymic epithelial cells with loss of thymopoietin in vivo. Thus viral cell transformation is followed by non-rigid but persistent membrane fluidization interfering with only selective receptor expression.

Animals↗

[Postoperative syndromes and recurrence in highly selective vagotomy].

In a prospective multicenter trial the clinical results and recurrences after proximal gastric vagotomy (PGV) in different gastroduodenal ulcer types have been investigated. Pyloric and prepyloric ulcers showed a significantly higher recurrence rate after PGV without drainage than duodenal and gastric ulcers. The secretory pattern could not explain the failure of PGV in these two ulcer types, which exhibit an alteration of the muscular layer at the pylorus and the distal antrum, a so called antropyloric dystrophy. About 60% of the recurrent ulcers after PGV stay asymptomatically. A refined concept for surgical treatment of peptic ulcer is proposed.

Adolescent↗