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Biomedical subjects

K Korte

Publications and source records attributed to K Korte.

At least 19 recordsLinked to original sources
PubMed1994

Cardiovascular protection by postmenopausal estrogen replacement therapy: possible mechanisms of the estrogen action.

Estrogen replacement therapy reduces the cardiovascular risk in postmenopausal women, but the mechanism has yet to be evaluated. There is growing evidence that estradiol administration results in direct vasodilatory effects on vessel walls. The biochemical mechanisms have been investigated in human arteries and veins with respect to different mediators and cell systems. Whereas estradiol had no direct effect on the prostaglandin system we found a endothelin-mediated stimulation of prostacyclin production in endothelial cell cultures. In experiments with the NO/cGMP-system estradiol activity could be demonstrated. In addition estradiol provoked an increase in the intracellular Ca2+ concentration. These results indicate that several mechanisms may be involved in the vasodilating effect of estradiol.

Calcium↗
PubMed1994

[Does estradiol modify the NO/cGMP system of blood vessels? Studies of the mechanism of cardiovascular protection by estrogen substitution in the postmenopausal period].

The effect of estradiol on the vasodilating NO/cGMP-system has been investigated in vitro and in vivo. Measurements of cGMP were carried out, cGMP values reflecting NO production. The incubation of human leg vein homogenates (n = 15) for 15 min. with estradiol in the concentrations 10(-6) M, 10(-7) M and 10(-8) M showed at 10(-8) a slight increase of the cGMP-concentrations. Due to high variation compass the difference to the control value was not statistically significant. The clinical part of the study included postmenopausal women, 20 were treated with transdermal estradiol patches (TTS, 0.05 mg/die) and 20 with estradiolvalerate orally (2 mg/die). There were 3 drop outs, 1 in the transdermal estrogen group, 2 in the oral estrogen group. In both groups there were no considerable differences in urinary cGMP concentrations. Thus, these results didn't clearly indicate an involvement of the NO/cGMP-system in the cardioprotective effect of an estrogen substitution therapy in postmenopausal women. Since former investigations are indicative of complex interactions of different vasoactive systems and of the requirement of longer treatment periods for an action of estradiol, an effect on the NO/cGMP-system cannot be ruled out.

Administration, Cutaneous↗
PubMed1993

Characterization of the cardiac troponin I phosphorylation domain by 31P nuclear magnetic resonance spectroscopy.

Cardiac holotroponin can be phosphorylated at serine 23 and/or 24 in the heart-specific region of bovine troponin I. When isolated freshly it is composed of a mixture of non-, two mono-, and bisphosphorylated species. At neutral pH the monophosphorylated form carrying phosphate at serine 24 yields a resonance signal at 4.6 ppm and that carrying phosphate at serine 23 at 4.4 ppm; the two phosphate groups of the bisphosphorylated form yield only one 31P-NMR signal at 4.2 ppm. From the chemical shift dependence on pH, pKa values have been estimated to be 5.3 and 5.6 for the phosphate groups at serine 24 and serine 23, respectively. Both phosphates of the bisphosphorylated form exhibit very similar pKa values of approximately 5.8. Separation of bisphosphotroponin I from the complex results in a downfield shift and the appearance of two 31P-NMR signals at positions comparable to those of the two monophospho forms. Complex formation of cardiac troponin I with C or T does not alter the spectrum obtained with isolated troponin I; however, the original troponin spectrum is restored by reconstitution of the holocomplex from all three components T, I, and C. Two signals are also observed with a bisphosphorylated synthetic peptide [PVRRRS(P)S(P)ANYR] representing the phosphorylation domain. pKa values of about 5.3 and 5.6 have been determined for serine 7 (corresponding to serine 24 of troponin I) and serine 6 of the peptide (corresponding to serine 23 of troponin I).

Amino Acid Sequence↗
PubMed1993

The production of prostanoids and the identification of macrophages in human decidua vera tissue.

In decidual tissues of first trimester therapeutic abortions we have identified a large macrophage population that is stained by a specific antibody (Ki-M8). Also, we evaluated the capacity of decidual cells, obtained before and after labor, to synthesize prostanoids from radiolabeled arachidonic acid. Decidua collected after vaginal delivery produced significantly more prostaglandin (PG) F2 alpha, PGE2 and thromboxane (TX) B2 (7.4 +/- 1.3, 7.2 +/- 1.3, 11.7 +/- 1.1 pmol/mg protein/4 h, mean +/- SD, respectively) than did tissues from women who had caesarean sections (3.3 +/- 0.8, 1.4 +/- 0.5, 6.3 +/- 1.8 pmol/mg protein/4 h, respectively). Moreover, PGF2 alpha and PGE2 were rapidly converted to their 13,14-dihydro-15-keto-metabolites particularly in tissues obtained after vaginal delivery. All this lends further support to the proposition that decidual activation may be important in the onset of labor.

Abortion, Therapeutic↗
PubMed1993

Natural and synthetic estrogens and prostacyclin production in human endothelial cells from umbilical cord and leg veins.

We have evaluated the effects of 17 beta-estradiol and 17 alpha-ethinylestradiol on prostacyclin production (measured as prostaglandin-6-keto-F1 alpha) in human endothelial cell cultures that had been obtained from umbilical cord and from leg veins. Endothelial cultures were treated with the estrogens at 3 different concentrations (10(-6), 10(-7), 10(-8) M) for up to 72h. 17 beta-estradiol did not affect basal 6-keto-PGF1 alpha production in these cell cultures. With 17 alpha-ethinylestradiol the synthesis of 6-keto-PGF1 alpha was not statistically significant changed. At least in our in vitro system we could not find an effect of natural and synthetic estrogens on 6-keto-PGF1 alpha production. This does, of course not rule out an effect in the more complex in vivo-situation.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

The effect of 17 beta-estradiol and endothelin 1 on prostacyclin and thromboxane production in human endothelial cell cultures.

The effect was investigated of endothelin 1 and 17 beta-estradiol on prostacyclin and thromboxane A2 production (determined as the stable metabolites 6-keto-PGF1 alpha and thromboxane B2, respectively) in endothelial cell cultures obtained from veins of human umbilical cord. There was a statistically significant increase of 6-keto-PGF1 alpha production with endothelin 1 at concentrations of 10(-8) and 10(-9) M [9.5 +/- 1.1% and 7.2 +/- 0.9%, (mean +/- SD, n = 5), respectively] compared to basal production. In contrast, 17 beta-estradiol alone (10(-6) and 10(-8) M) had no effect. In the presence of 17 beta-estradiol (10(-8) M) the stimulating effect of endothelin 1 (10(-8) and 10(-9) M) on 6-keto-PGF1 alpha production was further enhanced to 60.0 +/- 22.5% and 39.5 +/- 22.1%, respectively, compared to basal values. With respect to thromboxane B2, no change in its production was observed by the addition of endothelin 1 and 17 beta-estradiol, alone or in combination in the concentrations mentioned above. These results indicate that 17 beta-estradiol potentiates the effects of endothelin 1 on prostacyclin production in human endothelial cells.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

The effect of vanadate of arachidonic acid metabolism in human amnion cells.

This investigation was designed to investigate the effects of vanadate on arachidonic acid metabolism in human amnion cell in primary monolayer culture that served as a model system. The secretion of prostaglandin E2 (PGE2) into the culture medium was quantified by radioimmunoassay. The rate of conversion of [14C] arachidonic acid to [14C] PGE2 (PGE2 synthase) was determined in cell sonicates under optimal in vitro conditions. A maximal stimulation of PGE2 production and PGE2 synthase activity was determined with vanadate at a concentration of 32 microM) was effective maximally after 4 h of treatment, i.e., the production of PGE2 was stimulated 2,3-fold, and the specific activity of PGE2 synthase 2,1-fold compared with control incubations, respectively. We suggest that vanadate acts to increase the rate of conversion of arachidonic acid to PGE2 by a mechanism that involves de novo protein synthesis or that alters the phosphorylation state of enzymes that are requisite for the conversion of arachidonic acid to PGE2.

Amnion↗
PubMed1993

Vanadate, epidermal growth factor and prostaglandin E2 production in human amnion cells.

We have investigated the effects of vanadate (VAN) and mouse epidermal growth factor (mEGF) on prostaglandin (PG) E2 production in human amnion cells in monolayer culture that served as a model system. The secretion of PGE2 into the culture medium was quantified by radioimmunoassay. The rate of conversion of [14C] arachidonic acid to [14C] PGE2 (PGE2 synthase) was determined in cell sonicates under optimal in vitro conditions. After a treatment period of 4 h we observed an increase in PGE2 production in the presence of mEGF (4.7-fold), VAN (1.8-fold) or both agents (6.8-fold) over control samples. Similarly, the specific activity of PGE2 synthase was stimulated maximally after 4 h with mEGF (2.1-fold), VAN (1.7-fold) or with both (4.8-fold) compared with untreated tissue samples. In the presence of cycloheximide those effects were abolished. We suggest, that VAN and mEGF act by a mechanism(s) that involves de novo protein synthesis or that alters the phosphorylation state of enzymes that are requisite for the conversion of arachidonic acid to PGE2.

Amnion↗
PubMed1993

The effects of vanadate and epidermal growth factor on the specific activities of phospholipase A2 and phosphatidylinositol-specific phospholipase C in human amnion cells.

We have evaluated the specific activity of phospholipase A2 (PLA2) and phosphatidylinositol-specific phospholipase C (PLC) in human amnion cells in monolayer culture that had not (CTL) or that had been treated with vanadate (VAN) and/or mouse epidermal growth factor (mEGF) for 4 h. It is known that both agents stimulate prostaglandin (PG) E2 synthesis in these cells. Phospholipase enzyme activities were determined in the 750 x g supernatant fraction of amnion cell homogenates under optimal in vitro conditions. The specific activity of PLA2 ranged from 1.1 to 1.25 nmol/mg protein/0.5 h and that of phosphatidylinositol-specific PLC from 1.04 to 1.2 mumol/mg protein/h. Treatment of amnion cell cultures with VAN and/or mEGF had no statistically significant effect on the specific activities of either phospholipases. Thus, we conclude that the stimulation of PGE2 production by VAN and mEGF is not due to an increase in the release of arachidonic acid from glycerophospholipid storage forms in human amnion cells.

Amnion↗
PubMed1992

Thrombocytopenia in the HELLP syndrome is not due to platelet-associated IgG (PAIgG).

The presence of membrane-bound and circulating platelet-associated IgG (PAIgG) in nine pregnant women with hemolysis, elevated liver enzymes, and low platelet count (HELLP syndrome) was investigated. The reference group consisted of 21 patients with chronic idiopathic thrombocytopenic purpura (ITP). In the majority of patients with ITP, thrombocytopenia results from the binding of PAIgG to the platelet membrane with subsequent platelet destruction. In none of the patients with HELLP syndrome membrane-bound or circulating PAIgG was found. By contrast, membrane-bound and circulating PAIgG was detected in 15 of the 21 cases of chronic ITP (71.4%). These findings suggest that platelet destruction in patients with HELLP syndrome does not result from the binding of PAIgG to the platelet membrane. Therefore, the treatment of thrombocytopenia in this syndrome with immunosuppressants (e.g., corticosteroids), as in chronic ITP, does not seem appropriate.

Alanine Transaminase↗
PubMed1992

Eicosanoid production in human umbilical cord vessels: effect of 17 beta-estradiol.

This study was designed to investigate the effects of 17 beta-estradiol on prostanoid formation from exogenous arachidonic acid in homogenates of human umbilical cord vessels. The veins produced more prostanoids than the arteries and predominantly 6-keto-PGF1 alpha. 17 beta-estradiol had no effect on the rate of production of prostanoids in either vessels. Thus, at least in our in vitro system, the regulation of the vascular tone by prostanoids seems not to be altered by the addition of 17 beta-estradiol.

Arachidonic Acid↗
PubMed1992

[Production of prostacyclin in human umbilical cord blood vessels. Effect of natural and synthetic estrogen].

This investigation was conducted to evaluate the effects of 17 beta-estradiol and 17 alpha-ethinylestradiol on prostacyclin PGI2-production in homogenates of human umbilical cord arteries and veins in the presence of exogenous arachidonic acid. The incubation of 17 beta-estradiol at 2 different concentrations (10(-8) and 10(-6) M) in the presence of arachidonic acid for various times (5 min up to 24 h) effected an increase in the production of PGI2 (measured as 6-keto-prostaglandin F1 alpha) of 36-47% in the artery and 16-21% in the vein over basal values (100%). Under the same experimental conditions with 17 alpha-ethinylestradiol we observed an increases of 30-40% in the artery and 1-18% in the vein compared with basal values. For both estrogens this was not significantly different compared with untreated samples. In our in vitro system, natural and synthetic estrogens had no clear effect on PGI2 production in homogenates of human umbilical vessels.

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Epidermal growth factor stimulation of prostaglandin E2 biosynthesis in amnion cells. Induction of prostaglandin H2 synthase.

Amnion is believed to be a tissue of signal importance, anatomically and functionally, in the maintenance of pregnancy and during the initiation of parturition. Epidermal growth factor (EGF)-like agents cause a striking increase in the secretion of prostaglandin E2 (PGE2) in human amnion cells but only if arachidonic acid is present in the culture medium. To investigate the regulation of arachidonic acid metabolism by EGF-like agents in amnion, we used mEGF and human amnion cells in primary monolayer culture as a model system. The amount of PGE2 secreted into the culture medium was quantified by radioimmunoassay and the rate of conversion of [14C]arachidonic acid to [14C]PGE2 (PGH2 synthase activity) in cell sonicates was determined under optimal in vitro conditions. Treatment of amnion cells with mEGF led to a marked increase in the rate of production of PGE2. The specific activity of PGH2 synthase (viz. the combined activities of prostaglandin endoperoxide (PGH2) synthase and PGH2-PGE isomerase) was increased by 2-5-fold in cells treated with mEGF. Treatment of amnion cells with mEGF for 4 h did not affect the specific activities of phospholipase A2 or phosphatidylinositol-specific phospholipase C. By immunoisolation of newly synthesized, [35S]methionine-labeled PGH2 synthase, we found that mEGF stimulated de novo synthesis of the enzyme. Thus, mEGF acts in human amnion cells in primary monolayer culture to increase the rate of PGE2 biosynthesis by a mechanism that involves induction of PGH2 synthase; the manifestation of EGF action on PGE2 biosynthesis is dependent on the presence of nonesterified arachidonic acid.

Amnion↗
PubMed1986

Separation and quantitation of fatty acids by high-performance liquid chromatography.

To facilitate the determination of the fatty acid composition of tissues and the investigation of fatty acid metabolism, we developed a method for the rapid separation by high-performance liquid chromatography and quantitation (by ultraviolet light absorption) of p-bromophenyl esters of fatty acids which vary in chain length from 10 to 22 carbon atoms. The utility of the method was demonstrated by evaluating the fatty acid composition of human uterine decidua vera tissue and human endometrial stromal cells that are maintained in monolayer culture.

Chromatography, High Pressure Liquid↗
PubMed1986

Response of human amnion cells in culture to 1,25-dihydroxycholecalciferol: increased 25-hydroxycholecalciferol 24-hydroxylase activity and prostaglandin E2 formation.

We investigated the possibility that 1,25-dihydroxycholecalciferol acts in human amnion as a physiologic calcium ionophore to effect increased prostaglandin E2 production in this tissue. This possibility was based on the propositions that this metabolite of vitamin D3 acts in other target tissues, that is, bone, intestine, chorioallantoic membrane, kidney, and intestine, to effect increased calcium absorption, that 1,25-dihydroxycholecalciferol is present in amniotic fluid, which bathes the amnion, and that the mobilization of calcium in amnion is associated with stimulation of enzymes, namely, phospholipase A2 and phosphatidylinositol-specific phospholipase C that act ultimately to effect the release of arachidonic acid, which in turn leads to increased prostaglandin E2 production. We found that human amnion cells, maintained in primary monolayer culture, are responsive to 1,25-dihydroxycholecalciferol. Treatment of these cells with 1,25-dihydroxycholecalciferol for 18 hours brought about the induction, in a dose-dependent manner, of 25-hydroxycholecalciferol 24-hydroxylase, a marker of 1,25-dihydroxycholecalciferol action. In addition, treatment of human amnion cells in monolayer culture with 1,25-dihydroxycholecalciferol caused, within 12 hours, a significant increase in the synthesis of prostaglandin E2, which was maintained for the duration of treatment, that is, 48 hours. These findings may be indicative of a significant physiologic role for 1,25-dihydroxycholecalciferol in metabolic processes that are important in amnion, including transport, amniotic fluid volume homeostasis, and the initiation of parturition.

Amnion↗
PubMed1986

Prostaglandin E2 9-ketoreductase activity in human decidua vera tissue.

Amnion is believed to be a tissue of central importance in the biochemical processes of parturition. In this tissue, prostaglandin E2 is the near exclusive prostaglandin produced. And although the production of prostaglandin E2 is increased during labor in women, the levels of the major metabolite of prostaglandin E2 in maternal plasma are not elevated; rather, the levels of 13,14-dihydro-15-ketoprostaglandin F2 alpha, the major circulating metabolite of prostaglandin F2 alpha, are increased strikingly. Because of this apparent paradox, we considered the possibility that prostaglandin E2, originating in amnion, chorion laeve, or decidua vera, is converted to prostaglandin F2 alpha in decidua vera by the action of prostaglandin E2-9-ketoreductase. We found that prostaglandin E2 9-ketoreductase, the enzyme that catalyzes the conversion of prostaglandin E2 to F2 alpha, is present in cytosolic fractions prepared from homogenates of uterine decidua vera tissue. The specific activity of 9-ketoreductase in cytosolic fractions of decidua of six women varied from 3.2 to 155 pmol X min-1 X mg-1 protein. We also evaluated the conversion of exogenous prostaglandin E2 to F2 alpha in intact human endometrial stromal cells in monolayer culture. We found that prostaglandin E2, added to the culture medium, was converted to prostaglandin F2 alpha by endometrial stromal cells that were maintained in the presence of inhibitors of prostaglandin synthase. The extent of conversion of exogenous prostaglandin E2 to F2 alpha, however, was low relative to the specific activity of prostaglandin E2 9-ketoreductase found in decidual cytosol. These findings are consistent with the possibility that prostaglandin E2 formed in decidua vera tissue may be converted in that tissue to prostaglandin F2 alpha by 9-ketoreductase; on the other hand, prostaglandin E2 formed in contiguous tissues probably is not converted significantly to prostaglandin F2 alpha by decidual 9-ketoreductase.

Cytosol↗