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W Seifert

Publications and source records attributed to W Seifert.

At least 91 records · Page 5Linked to original sources

Growth factors and gangliosides: a possible new perspective in neuronal growth control.

For many permanent cell lines the transition from a growing (P) to a resting (R) state is reversibly controlled by growth factors present in serum. This P-to-R transition was studied in a neuronal cell line (B104) with respect to the action of serum, dibutyryl cyclic AMP (DBcAMP), gangliosides, and a glioma cell-produced growth factor GGF. In this cell system gangliosides seem to act as differentiation and survival factors. The kinetics of uptake of radioactively labeled gangliosides and survival experiments both support the idea of the stable incorporation of exogenously added gangliosides into the cells. Based on the experimental evidence a new model of cell development is proposed. Thus in addition to the R or Go state, which in this cell system is rather unstable and probably regulated by cyclic nucleotides, we postulate a differentiated D state, which is controlled by gangliosides and which is characterized by its stability (survival time). This D compartment seems to be closer to the in vivo differentiated neuron than does the R or P state. tthe possible mechanisms for the action of gangliosides are discussed.

Animals↗

[Fibrinolytic therapy in deep venous thrombosis of the upper and lower extremity].

Fibrinolytic therapy was carried out in 59 patients suffering from a total of 60 deep venous thromboses of the iliac segment (n = 24), the femoropopliteal segment (n = 18), the deep calf veins (n = 2), or the subclavian vein (n = 16). 46 patients received streptokinase (SK), 4 were given urokinase (UK), and 10 were treated with streptokinase followed by urokinase (SK + UK). The duration of fibrinolytic therapy was between 19 and 596 hours (x = 166 +/- 111 hrs). Phlebographic examination was used to determine the location of the thrombotic occlusion as well as to evaluate therapeutic results. To assure sufficient anticoagulatory protection during therapy with streptokinase the dose of streptokinase was either reduced by steps of 20,000 U/hr to a minimum of 40,000 U/hr or heparin was added as a continuous infusion. Urokinase was administered with a mean loading dose of 75,000 IU followed by an average maintenance dose of 40,000 IU/hr; it was always given in combination with heparin. When therapeutic success was graded as complete/partial/no recanalisation, the following results were obtained: thrombotic occlusion up to 1 week old 35%/48%/17%; up to 2 weeks old 57%/14%/29%; 3 or 4 weeks old 12%/38%/50%; older than 4 weeks 13%/37%/50%. The two most common side effects were a fall of the hemoglobin and a rise of body temperature. Treatment with SK had to be interrupted for bleeding in two cases. One patient diet after rupture of the liver and of the spleen following development of subcapsular hematoma in these organs, 3 patients survived pulmonary embolism without major long-term impairment. Considering medical and social aspects (preservation of capability for working in young adults) it appears justified to administer fibrinolytic agents up to a thrombus age of 14 days, in some cases even up to a thrombus age of 28 days. Good results in cases of deep vein thrombosis of the lower limbs are often obtained only when fibrinolytic therapy is extended beyond 96 hours. It should be performed in intensive care units only. Follow-up examinations of the venous drainage capacity up to 2 years after fibrinolytic therapy document the good therapeutic effect that is warrented by streptokinase or urokinase induced complete recanalisation.

Adolescent↗

[Determination of normal values by means of various statistical methods derived from radioiodine tests (author's transl)].

Normal values derived from 361 euthyroid patients were calculated by means of five different statistical methods and compared. Borderline values were also obtained from 61 patients with hyperthyroidism, nine with hypothyroidism and ten with autonomous adenomas. The following individuals data were collected: 131 I-PBI after 48 hours, thyroid uptake after two, 24 and 48 hours.

Evaluation Studies as Topic↗

Cyclic nucleotides and cell growth.

Growth induction in resting fibroblast cultures by serum or growth factors induces a fast, transient cGMP peak which may constitute the intracellular signal for growth. A similar cGMP peak occurs when 3T3 cells arrested at the restriction point or in G0 by starvation for certain amino acids are induced for growth by readdition of the lacking nutrients. Both 3T3 and SV3T3 cells which are arrested randomly all around the cell cycle do not exhibit major changes in cyclic nucleotides after growth induction. Determination of intracellular cAMP and cGMP levels in normal and transformed fibroblasts under different growth conditions shows that the transition between growing and resting state (G0 arrest) is accompanied and probably induced by characteristic changes in cAMP to cGMP ratios. cGMP is decreased 2-5-fold in resting as compared to growing cultures, and increased 10-20-fold in activated cultures 20 min after serum induction. No major cGMP change was observed in growing, confluent, or serum-activated cultures of transformed cells. Measurement of guanylcyclase under unphysiological conditions (2 mM Mn++) in crude and purified membranes from 3T3 and SV3T3 cultures did not show increased enzyme activity in the transformed cells. Significant differences may only show up when synchronized cells pass through the restriction point in G1 phase. As a hypothesis it is proposed that transformed cells have an activated guanylcyclase system or a relaxed cGMP-pleiotypic response mechanism at the restriction point of their cell cycle.

Animals↗

Cyclic nucleotides and growth control in cultured mouse cells: correlation of changes in intracellular 3':5' cGMP concentration with a specific phase of the cell cycle.

The commencement of cell growth following serum addition to quiescent cultures of mouse fibroblasts is preceded by transient changes in intracellular concentrations of cAMP and cGMP. By artificial depletion of the culture medium for different nutrients, cell growth can be reversibly arrested in various phases of the cell cycle. Here it is shown that the major cGMP increases are only observed when cultures which are arrested in the G(0) phase are stimulated to grow or when synchronized growing cells pass through the G(1) phase. In addition to its concomitant decrease, cAMP exhibits rhythmic changes during the cell cycle. This suggests that the increase in cGMP could act as a specific signal for movement of cells out of the G(0) or G(1) phase of the cell cycle by activating the pleiotypic and mitogenic program of the cell.

Animals↗

Growth control in cultured mouse fibroblasts: induction of the pleiotypic and mitogenic responses by a purified growth factor.

Addition of serum to quiescent mouse fibroblasts induces a series of macromolecular changes (a pleiotypic response) followed by DNA synthesis and cell division. A new pituitary hormone, fibroblast growth factor, and hydrocortisone acting at physiological concentrations can completely replace exogenously added serum for the induction of these events in lines of BALB/c 3T3 cells. The induction of cell growth is specific for cultured fibroblasts; no stimulation is observed for mouse epithelial cells or virally transformed fibroblasts.

Animals↗