[Synthesis of n-substituted amino acid-p-nitrobenzyl esters as potential ACE inhibitors].
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to G Heder.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
A bovine brain fraction with FGF activity (fibroblast growth factor) increased the formation of granulation tissue of rats in an experimental wound healing model. It was characterised by intensified formation of new capillaries, stimulation of the synthesis function of fibroblasts and myofibroblasts, and proliferation of freshly developed granulation tissue. The results obtained from light microscopy and autoradiographic electron microscopy with 3H-thymidine suggested significant increase in the labelling of activated, undifferentiated endothelial cells in vascular sprouts and of differentiated endothelial cells in developed capillaries. FGF S3 appeared to speed up the differentiation of freshly formed endothelial cells. Also labelled were pericytes and other fibroblastoid cells, undifferentiated mesenchymal cells, juvenile undifferentiated fibroblasts, mature fibroblasts, myofibroblasts, and macrophages. Pericytes are presumed to be preferential precursors of myofibroblasts, on account of their occurrence in time and similar ultrastructural parameters. Close neighbourhood of lymphocytes and labelled fibroblasts gave rise to the assumption of specific effects, such as stimulation by lymphokines.
The influence of corpus luteum extract on the growth of mouse embryo fibroblast monolayer cultures is stronger in sparse cultures than in dense ones. Its growth-stimulating activity seems to be somehow higher in glass bottles than in plastic dishes. Corpus luteum extracted from pig and/or cattle acted in a similar way.
A functionally and structurally well-defined calf aortic endothelial cell line has been used to characterize tissue preparations with mitogenic activity by means of cell proliferation kinetics. The following preparations were tested: An extract from corpora lutea (pig), produced by stepwise ammonium sulfate precipitation (CL-S3), a fraction obtained from CL-S3 extract by ion exchange chromatography (CM-S4), and a chorioallantoic membrane preparation (CAM preparation). Under optimal cultivation conditions 100 micrograms CL-S3, 5 micrograms CM-S4, or 100 micrograms CAM preparation per ml medium increased the cell number and growth rate of the endothelial cells in approximately like manner after an incubation period of 48 hours. Compared with CL-S3 these results demonstrate a 20 fold enrichment of the mitogenic activity in the CM-S4 fraction. Under suboptimal cultivation conditions (i.e. a low cell number at the seeding and a reduced nutritive quality) 100 micrograms CL-S3 per ml medium stimulated the cell proliferation up to 12 times at the end of a 6-days-cultivation-period. These results are discussed in connection with the use of these preparations in the angiogenesis research and with respect to the application of selected preparations in cell culture media in order to reduce the serum concentrations.
Fractions of extracts of porcine corpora lutea, of bovine brain with fibroblast growth factor activity and whole blood serum versus plasma derived serum were tested using Boyden technique and agarose migration with regard to their influence on the migration behaviour of endothelial cells of calf aortas. All factors showed a concentration dependent stimulation of random migration of the cells. Only whole blood serum versus plasma derived serum had chemotactic activity. Thus it must be supposed that vascularization processes will be only favoured by the first mentioned two factors whereas angiogenesis will be possibly triggered by factors released from blood platelets during blood coagulation.
In rats with polyvinyl rings implanted under the dorsal skin, the formation of granulation tissue was found to be stimulated by application of brain extract with fibroblast growth factor (FGF) S3 activity which had been obtained from cattle. This stimulating effect on wound healing proved to depend on doses and was detectable in rats aged two and six months on the third and seventh postoperative days. The desired action could be induced only by repetitive administration of FGF S3 or by coupling of the latter to SYSpur-derm, a synthetic dermatoplastic material. More fractions with potential action upon formation of granulation tissue proved to be obtainable from further biochemical separation of FGF S3. One of such fractions was successfully concentrated to a potentiality by which one tenth of the normal dose yielded the same effect as the full dose. Hexosamine and hydroxyproline levels were measured, at the same time, and found to stimulate fibroblasts. The findings are discussed.
Reported in this paper are studies by which evidence was produced to increased formation of granulation tissue in rats, aged two and six months, seven days after repeated localised administration of brain extract from cattle with FGF activity (fibroblast growth factor). Such increased formation of granulation tissue was attributable to the formation in the same granulation tissue of larger amounts of capillaries, which actually provided conditions for better blood supply. The above increase was associated with stimulation of the synthetic function of fibroblasts and myofibroblasts in the granulation tissue. Comprehensive morphometric tests, including differential counting, appeared to show that additional effects had to be assumed, in particular on macrophages and lymphocytes. Such increase in angiogenesis seemed to suggest that in the in vivo model studied FGF proved to be, first of all, a factor of angiogenesis rather than a factor of fibroblast growth. The above results, as obtained from rats which differed in age, exhibited a certain variation in response to FGF. This seems to underline the importance of age-dependent examination also in the context of pharmacological studies.
Explore the source record for details and available documents.
In cultures of calf aorta endothelial cells treated with extracts from corpora lutea a paradoxical effect occurred: Cell proliferation was regularly stimulated, but DNA synthesis was more or less inhibited. This inhibition was related to the presence of 3H-thymidine and could be reduced by lowering te 3H-thymidine concentration in the incubation medium. To decide whether the molar concentration or the activity of the 3H-thymidine was responsible for this effect, unlabelled thymidine was added to increase the molar thymidine concentration. A mixture of unlabelled thymidine and 3H-thymidine (ratio 200:1) added to the medium at various concentrations stimulated the DNA synthesis in a dose-dependent was up to 4.1 x 10(-6) M. Furthermore, nonradioactive thymidine slightly promoted the proliferation of calf aorta endothelial cells up to 10(-6) M independently of the presence or absence of corpus luteum extract. It is concluded that the radioactivity of 3H-thymidine is responsible for this effect. Internal 3H-beta radiation may perturb cell cycle progression after incorporation of this radioactive precursor into the cells. This view is supported by the fact that the inhibitory effect can be reduced by adding unlabelled thymidine, i.e. by lowering the specific activity of 3H-thymidine. On the other hand, increasing concentrations of growth promoting factors which stimulate the uptake of 3H-thymidine render the cells more sensitive to this effect.
Porcine and bovine corpora lutea contain an activity capable of stimulating the initiation of DNA synthesis of mouse embryo fibroblasts, calf aorta media cells, and calf aorta endothelial cells. After fractionation of extracts produced by gradual ammonium sulfate precipitation by means of ion exchange chromatography on CM-Sephadex the activity is especially enriched in the last fraction (peak 5). The initiation of the DNA synthesis of calf aorta endothelial cells, however, is strongly dependent on the concentration of the labelled thymidine in the incubation medium. Calf aorta endothelial cells significantly respond to this corpus luteum factor only at a reduced 3H-thymidine concentration of 9.25 nM. At a 3H-thymidine concentration of 37 nM at which mouse embryo fibroblasts and calf aorta media cells respond with a dose-dependent stimulation of DNA synthesis, calf aorta endothelial cells only show a dose-dependent inhibition of the 3H-thymidine incorporation into the DNA. The relationship of this factor to the known growth factors and to the corpus luteum angiogenic factor (CLAF) deserves further investigation.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
From bovine brains a fraction with fibroblast growth factor activity was prepared according to the method given by Gospodarowicz et al. (1978) and tested regarding to its biological effectiveness on articular cartilage regeneration in rabbits the cartilage in one knee-joint of those had been injured in a defined manner. The intraarticular administration of the brain fraction supported the healing process of the intrachondral lesions by conspicuously increasing the chondrocyte proliferation starting from preexisting cartilage tissue. In the case of subchondral lesions the neodifferentiation of chondrocytes out of the simple connective tissue that primarily filled the defect was promoted significantly.
A bovine brain fraction with fibroblast growth factor (FGF) activity was prepared according to the method described by Gospodarowicz et al. and its influence on the healing process of experimentally produced intrachondral lesions in the knee-joint of rabbits was studied. Intraarticular administration of this preparation resulted in a substantial stimulation of the proliferation of "cluster cells", a special kind of chondrocytes which accumulate and form clusters.
Explore the source record for details and available documents.
The angiogenic activity in corpus luteum (corpus luteum angiogenesis factor--CLAP) reported first by us in 1977 was enriched by ammonium sulfate precipitation and further purified by ion exchange chromatography. Extracts produced in this way from corpora lutea of cyclus synchronized pigs have proven effective to stimulate DNA synthesis and proliferation of both calf aorta endothelial cells and primary mouse embryo fibroblasts cultivated either under optimal or suboptimal (depletion) conditions. The mitogenic action of these extracts has been found to be dose-dependent and similar to that of bovine brain extract produced according to the preparation method published by GOSPODAROWICZ.