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J Patsch

Publications and source records attributed to J Patsch.

10 recordsLinked to original sources

Stimulation of human early and late erythropoietic progenitor cells by insulin: evidence for different mechanisms.

In order to investigate cellular mechanisms involved in insulin stimulation of erythropoiesis, we have studied the response of early (BFU-e) and late (CFU-e) erythroid progenitor cells in a serum-free agar culture system. In this assay system, CFU-e proliferation occurred in media containing low-density lipoproteins, bovine serum albumin, transferrin and recombinant erythropoietin (rEPO). Insulin in physiological concentrations as low as 10(-12)M, added directly to cultures, augmented CFU-e colony formation. This stimulatory effect was also seen when monocyte- and T lymphocyte-depleted cells from normal donors were cultured. In contrast, BFU-e was not stimulated by media devoid of insulin. Occurrence of BFU-e colonies required the presence of insulin in concentrations higher than 10(-8)M. This insulin effect was not dependent on the presence of monocytes and T lymphocytes. Delayed addition studies of rEPO to insulin containing cultures revealed a slight but significant survival rate of CFU-e. A similar survival rate was found for BFU-e. From this, we conclude that insulin stimulates CFU-e by an EPO-like activity. For BFU-e, however, the decline in the number of bursts caused by EPO deprivation implies that insulin does not act directly as a burst-promoting activity but that it probably induces the release of this activity from non-adherent and T lymphocyte-depleted bone marrow cells.

Animals

Proliferation and differentiation of human erythropoiesis in vitro: effect of different human lipoprotein species.

In order to permit erythroid proliferation in agar, a serum-free system was developed based on McCoy's 5A medium at pH 8.0, containing deionized and delipidated bovine serum albumin, iron-saturated transferrin, and crude erythropoietin (step III). Addition of the entire complement of serum lipoproteins, termed lipoprotein fraction I (density, less than 1.21 g/ml), increased the number of erythroid colony-forming units and erythroid burst-forming units to numbers indistinguishable from those observed with media containing serum. Moreover, terminal differentiation occurred to fully hemoglobinized normoblasts and even mature erythrocytes. Under these conditions, the erythropoietin dose-response curve obtained when not using serum was comparable to that with serum. Colony formation also displayed a linear relationship to seeding densities down to limiting dilutions. For differential analysis of the main density lipoprotein fractions, sequential ultracentrifugation was performed to isolate very low-density lipoproteins, low-density lipoproteins (LDL), high-density lipoproteins2 (HDL2), and HDL3, which were then added individually to serum-free cultures. Of the main lipoprotein classes, LDL exhibited the most proliferative capacity, followed by HDL2 and HDL3. Our findings indicate that when serum is substituted by well defined compounds including highly purified lipoprotein fractions, a serum-like proliferation and differentiation of human erythropoietic progenitor cells in agar can be obtained.

Bone Marrow

[Measurement of global diffusion capacity for CO, membrane diffusion capacity for CO and capillary blood volume in patients with bronchial emphysema after fominoben HCl. Short- and long-time trials (author's transl)].

The effect of 3'-chloro-2'-(N-methyl-N-[(morpholino-carbonyl)methyl]-aminomethyl)-benzanilide hydrochloride (fominoben HCl, P-B 89 Cl, Noleptan) on the global and membrane diffusion capacities and on the capillary blood volume in patients with emphysematous bronchitis is described. All 3 parameters, independent of the severity of the emphysema and the resulting respiratory insufficiency, are increased. It can thus be concluded that fominoben by improving the ventilation-perfusion ratio leads to an enlargement of the active diffusion surface (capillary surface), from which the increase in the global diffusion capacity results. The site of action of fominoben for its positive effect on respiration is thus established as being in the alveoli.

Adult

Comparison of the effects of halofenate (MK-185) and clofibrate on plasma lipid and uric acid concentration in hyperlipoproteinemic patients.

The plasma lipid and serum uric acid lowering effect of halofenate (MK-185, 1 g/day) was compared with the action of clofibrate (2 g/day) in a double-blind 1-yr study in 23 patients with Type 2, 3, 4, and 5 hyperlipoproteinemia. It could be demonstrated that clofibrate decreased the plasma cholesterol concentration significantly to 75% and the triglyceride concentration to 49% of the placebo period level. Halofenate produced no consistent effect on plasma cholesterol but ther was an average reduction of the plasma triglyceride concentration to 84%, which was, however, not significant. If only the Type 4 patients were taken into account, a mean significant decrease to 47% of the triglyceride concentration was observed during the second 24-week period of treatment. In contrast, halofenate lowered the serum uric acid concentration significatnly to 77% of the placebo period level, whereas the decreasing action of clofibrate was weaker (88%) and of lesser significance.

Adult