Search PubMed⌕ Search

Biomedical subjects

R Müller

Publications and source records attributed to R Müller.

At least 649 records · Page 36Linked to original sources
PubMed1985

Analysis of the differentiation-promoting potential of inducible c-fos genes introduced into embryonal carcinoma cells.

To investigate the differentiation-promoting potential of c-fos in embryonal carcinoma cells (EC cells) we have designed various human metallothionein promoter-mouse-c-fos gene constructs containing also the selectable SV40 promoter-driven neo gene. Upon transfection into F9 EC cells and selection for neo resistance, the following results were obtained. (i) With each of the constructs, colonies of morphologically altered and differentiated (i.e., TROMA-1 and TROMA-3 expressing) cells were identified. (ii) Expression of c-fos was required to affect the differentiation state of F9 cells to a significant extent, but a low level was sufficient; no enhancement of differentiation was noticeable even after 100-fold induction of c-fos expression by cadmium. (iii) F9 cell clones were isolated which, in spite of very high levels of exogenous c-fos expression, had stem cell morphology. These cells, however, continuously generated morphologically altered and differentiated cells upon subculturing. (iv) In other EC cell lines, which resemble stem cells more closely than the 'partially differentiated' F9 cells, c-fos expression showed either a less pronounced (P19 cells) or no differentiation-promoting effect at all (PC13 cells). Our results suggest that the c-fos gene product acts in concert with other, probably 'spontaneously' occurring events to promote differentiation of certain EC cell lines.

Animals↗
PubMed1985

Persistence of the competent state in mouse fibroblasts is independent of c-fos and c-myc expression.

Induction of competence in quiescent fibroblasts by platelet-derived growth factor (PDGF) is accompanied by a dramatic increase in the expression of c-fos and c-myc genes. However, the maintenance of the competent state and progression through G1 does not require high expression of these proto-oncogenes. These results suggest that the induction of c-fos and c-myc by growth factors in quiescent fibroblasts may be required to render the cells competent for progression.

Animals↗
PubMed1985

Evidence for a correlation between nitric oxide formation by cleavage of organic nitrates and activation of guanylate cyclase.

According to our present understanding organic nitrates like glycerine trinitrate mediate their pharmacological effect by an intracellular stimulation of the enzyme guanylate cyclase (E.C. 4.6.1.2.) [1, 10]. The exact molecular mechanism underlying the process of enzyme activation is still a matter of controversial discussion. But there is general agreement in literature about the fact that organic nitrate compounds are able to activate the enzyme guanylate cyclase only in the presence or by the interaction of the amino acid cysteine [3, 5]. The stimulatory activity of nitric oxide-containing compounds may be due, at least in part, to the formation of active, unstable intermediate S-nitrosothiols, i.e. S-nitrosocysteine in case of the organic nitrates [7]. According to Craven and DeRubertis [2], the active intermediates of guanylate cyclase stimulation are represented by nitric oxide-heme complexes. There is, however, substantial evidence that the organic nitrates have to be cleaved before they become biologically active. During the transformation which takes place in the presence of cysteine or by means of enzymatic catalysis, nitric oxide radicals are reductively split off the molecule from which (via the intermediate formation of salpetric acid) the nitric oxide is liberated as the essential stimulatory agent. In this study we examined the transformation of glycerine trinitrate and other organic nitrates under the influence of different thiols and a purified soluble rat liver guanylate cyclase preparation. At the same time the stimulation of guanylate cyclase in the presence of the thiols mentioned was quantitatively estimated. Only in case of cysteine did we find a strict correlation between the liberation of nitric oxide from different organic nitrates and the degree of enzyme activation. Several other thiols were also able to liberate nitric oxide, but surprisingly enough, there was no equivalent stimulation of guanylate cyclase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Extended life span and tumorigenicity of nonestablished mouse connective tissue cells transformed by the fos oncogene of FBR-MuSV.

We have analyzed the transforming potential of two fos oncogene products in nonestablished cultures of mouse connective tissue cells: p55fos of FBJ-MuSV and p75gag-fos of FBR-MuSV. Although both proteins induced morphological transformation and colony formation at low cell density in a G418 resistance selection assay, p75gag-fos exhibited more pronounced transforming potential than p55fos. In addition, p75gag-fos-transformed cells overcame crisis with a high probability and were tumorigenic in syngenic mice. These properties of the FBR-MuSV appear to be linked to structural alterations in the p75gag-fos oncogene product. Polyoma virus large T protein complemented the transforming potential of fos, in that it not only increased the probability of establishment of fos-transformed cells but also enhanced fos-induced morphological transformation. Our results suggest that different oncogenes affect morphological transformation, low cell density growth, establishment, and tumorigenicity to various degrees.

Animals↗
PubMed1985

Cloning and expression of cDNA for rat heme oxygenase.

Two cDNA clones for rat heme oxygenase have been isolated from a rat spleen cDNA library in lambda gt11 by immunological screening using a specific polyclonal antibody. One of these clones has an insert of 1530 nucleotides that contains the entire protein-coding region. To confirm that the isolated cDNA encodes heme oxygenase, we transfected monkey kidney cells (COS-7) with the cDNA carried in a simian virus 40 vector. The heme oxygenase was highly expressed in endoplasmic reticulum of transfected cells. The nucleotide sequence of the cloned cDNA was determined and the primary structure of heme oxygenase was deduced. Heme oxygenase is composed of 289 amino acids and has one hydrophobic segment at its carboxyl terminus, which is probably important for the insertion of heme oxygenase into endoplasmic reticulum. The cloned cDNA was used to analyze the induction of heme oxygenase in rat liver by treatment with CoCl2 or with hemin. RNA blot analysis showed that both CoCl2 and hemin increased the amount of hybridizable mRNA, suggesting that these substances may act at the transcriptional level to increase the amount of heme oxygenase.

Amino Acid Sequence↗
PubMed1985

[Influence on immune function parameters in histiocytosis-X of thymostimulin].

Immune function (mitogen and antigen stimulation, suppressor cell activity, T-cell subpopulation distribution) and immunogenetics (HLA-gene determination) were studied in 13 patients with histiocytosis-X and in 88 healthy controls. We found three clusters with significantly different immune responses (F-values greater than 4-20, p less than 0.05-0.001) against mitogenic and antigenic stimulation among the controls which differed, too, in HLA-gene distribution. As suppressor cell activity and T-cell subpopulation distribution are the same in all three control clusters, these reactivity differences should be functional ones and may be genetically determined. Patients with histiocytosis-X show a significantly reduced suppressor cell activity and their helper cells are significantly reduced compared to the controls (p less than 0.01). Furthermore, their lymphocyte reactivity does not correspond with their immunogenetics, but is significantly reduced (p less than 0.05-0.001). Suppressor cell activity, helper cells and lymphocyte reactivity normalized in all eight patients treated systemically with thymostimulin (Tp-1 Serono). It seems to be possible therefore, to influence immunological aberrations in vivo by thymostimulin. In our opinion, the results of this study justify further investigations of the immunoregulatory mechanisms of histiocytosis-X and larger prospective clinical trials with thymic factors to find out, whether such a therapy may be a real alternative to the conventional therapeutic approach in this disease.

Adult↗
PubMed1985

[Visual evoked potential studies on human cortical coding of the speed of movement of a grating pattern].

Knowledge referring to the kind of velocity coding in human cortex can be obtained either by psychophysical methods or by recording of visually evoked cortical potentials (VEPs). With the help of adaptation experiments it is possible to distinguish between the additive and substitutive coding principle. VEPs were evoked by the onset of movement of a grating pattern (test stimulus). The most prominent waves N2 and P2 increased with accelerating test stimulus velocity within a range of 0.2-4 deg/s (see strong curve in Fig. 6a and 7a). Moving gratings (adaptation stimuli) were additionally presented in corresponding runs during the intervals between the test stimuli to attain a stable level of movement adaptation. The additional movement stimulation reduced the VEP amplitudes in general (see weak lines in Figs. 6a, 7a and relative amplitudes in Figs. 6b, 7b). When the adaptation stimulus velocity was raised within a range of 0.1-4 deg/s (see values of the abscissas in Figs. 6 and 7 indicated by symbols with arrow) the relative VEP amplitude became smaller (decrease from curve to x). This result points to the validity of the additive coding principle. The different behavior of the delta-curve supports the hypothesis of a second channel for velocities faster than 1 deg/s.

Adult↗
PubMed1985

Transient induction of c-fos and c-myc in an immediate consequence of growth factor stimulation.

Treatment of serum-deprived fibroblasts with serum or growth factors results in an immediate induction of the c-fos and c-myc proto-oncogenes. Maximal levels of c-fos mRNA are detected 30 minutes after treatment and maximal levels of c-myc mRNA are detected 60 minutes after treatment. The c-fos protein is expressed at high levels for about two hours following induction, yet the cell morphology remains normal. Thus, either an extended period of c-fos expression is required for cellular transformation, or the highly modified form of the fos protein, present in stimulated cells, is biochemically different from the transforming protein and is therefore not capable of inducing transformation. In this system, growth factor treatment results in mitogenesis. However, c-fos and c-myc are also induced in A431 cells, and in subclones derived from A431 cells, treated with epidermal growth factor (EGF). No correlation was found between the effects of EGF on A431 cell proliferation and the induction of c-fos and c-myc. Interestingly, the strongest inducer of c-fos in A431 cells was the calcium ionophore A23187. Induction occurred in almost 100% of the treated cells without prior serum deprivation or growth arrest. Treatment of HL60 cells with 12-0 tetra decanoylphorbol-13-acetate (TPA), which promotes macrophage-like differentiation, also induced c-fos with a time course similar to that observed in mitogen-treated fibroblasts. Thus, in HL60 cells, c-fos induction is associated with differentiation. In normal macrophages c-fos and c-myc can also be induced by CSF-1. However, the kinetics of induction are entirely different from those in growth factor-stimulated fibroblasts. Taken together, the data suggest a more general role for c-fos and c-myc in the transduction of growth factor signals received at the cell membrane, within the nucleus.

Animals↗
PubMed1985

[Fertility and Turner syndrome].

A case of Turner's syndrome (45,X/47,XXX) with one pregnancy is reported. Review of the literature revealed additional 31 cases of fertility in women with gonadal dysgenesis associated with a 45,X chromosomal line. Abortion and stillbirth are frequent and the rate of malformation is high.

Adult↗
PubMed1984

Incorporation of [18O]water into 4-hydroxybenzoic acid in the reaction of 4-chlorobenzoate dehalogenase from pseudomonas spec. CBS 3.

4-Chlorobenzoate is dehalogenated by 4-chlorobenzoate dehalogenase from Pseudomonas spec. CBS 3 to form 4-hydroxybenzoate. In 18O enriched water the hydroxygroup of 4-hydroxybenzoate is quantitatively labelled with 18O. This result clearly shows, that 4-chlorobenzoate dehalogenase catalyzes the hydrolytic cleavage of the halogen-carbon bond, without the involvement of molecular oxygen, a reaction not yet described.

Chromatography, Gas↗