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Biomedical subjects

A Kurtz

Publications and source records attributed to A Kurtz.

At least 253 records · Page 14Linked to original sources

Inhibition of renin secretion by platelet activating factor (acetylglyceryl ether phosphorylcholine) in cultured rat renal juxtaglomerular cells.

Acetylglyceryl ether phosphorylcholine (AGEPC), commonly known as platelet activating factor, was found to strongly inhibit renin secretion in cultures rich in juxtaglomerular cells. This inhibitory action of AGEPC was accompanied by an enhanced calcium permeability of the cell membrane as evaluated from measurements of the uptake of 45Ca. Simultaneous addition of the calcium channel blocker verapamil abolished the effects of AGEPC on both renin secretion and calcium permeability. Furthermore, addition of AGEPC to the cell cultures led to a decrease of 32P-labeled phosphatidylinositol 4,5-bisphosphate and to an increase in 3H-labeled diacylglycerol, indicating an activation of phospholipase C by AGEPC.

Animals↗

Hypoxia enhances prostaglandin synthesis in renal mesangial cell cultures.

In view of recent findings which suggest that renal prostaglandins mediate the effect of hypoxia on erythropoietin production, we have studied whether hypoxia is a stimulus for in vitro prostaglandin synthesis. Studies were carried out in rat renal mesangial cell cultures which produce erythropoietin in an oxygen-dependent manner. Production rates of PGE2 and in specified samples also of 6-keto-PGF1 alpha, as a measure of PGI2, and PGF2 alpha were determined by radioimmunoassay after incubation at either 20% O2 (normoxic) or 2% O2 (hypoxic) in gas permeable dishes for 24 hrs. Considerable variation in PGE2 production was noted among independent cell lines. PGE2 production appeared to be inversely correlated to the cellular density of the cultures. In addition, PGE2 production was enhanced in hypoxic cell cultures. The mean increase was 50 to 60%. PGF2 alpha and 6-keto-PGF1 alpha increased by about the same rate. These results indicate that hypoxia is a stimulus for in vitro prostaglandin production.

6-Ketoprostaglandin F1 alpha↗

Role of prostaglandins in hypoxia-stimulated erythropoietin production.

The role of prostaglandins in the mediation of hypoxia-stimulated erythropoietin (Ep) production by cultured rat renal mesangial cells was examined. It was found that an increase in prostaglandin E2 (PGE2) production accompanied the rise in Ep due to hypoxia (2% O2). The hypoxia-stimulated increase in Ep production was abolished in the presence of the cyclooxygenase inhibitor indomethacin (10(-5) M). When PGE2 (10(-6) M was added simultaneously with indomethacin, however, no diminution in hypoxia-stimulated Ep production was observed. Addition of arachidonic acid (AA, 10(-5) M), PGE2 (10(-6) M), or PGI2 (10(-4) M) enhanced Ep production under normoxic conditions (20% O2), while PGF2 alpha (10(-6) M) had no effect on Ep production. AA, PGE2, and PGI2 were found to stimulate adenosine 3',5'-cyclic monophosphate formation by the cultured mesangial cells. Enhancement of adenylate cyclase activity by forskolin (10(-5) M) also increased Ep production in the cell cultures. Our results suggest that hypoxia-stimulated Ep production by cultured mesangial cells is mediated by prostaglandins with subsequent stimulation of adenylate cyclase activity.

Adenylyl Cyclases↗

Activity in fetal bovine serum that stimulates erythroid colony formation in fetal mouse livers is insulinlike growth factor I.

In the present study, the erythropoietic activity of fetal serum was characterized. Using fetal bovine serum (FBS) as a source of the erythropoietic activity and serum-free cultures of fetal mouse livers (FMLC assay) as a detection system, we found that FBS stimulated colony formation from late erythroid progenitor cells (CFU-E) in a dose-dependent fashion. The slope of the dose-response curve, however, was significantly different from that for erythropoietin (Ep), the best-characterized erythropoietic activity so far. The erythropoietic activity of FBS was found in the 120-160- and 40-70-kD range at neutral pH. In the presence of 1 M acetic acid, however, the erythropoietic activity had an apparent molecular mass between 3 and 13 kD. From ion exchange experiments with DEAE-cellulose, the isoionic point of the activity was estimated to about pH 5. Furthermore, the erythropoietic activity of FBS was found to be co-eluted on Sephadex G-150 with the binding proteins of insulinlike growth factors (IGF). The IGF I concentration determined by radioimmunoassay was 70 ng IGF I/ml. The Ep activity of FBS was less than 5 mU/ml when determined with the posthypoxic polycythemic mouse assay for Ep. These results suggest that the erythropoietic activity of FBS is related to IGF and not to Ep. The erythropoietic activity of FBS was abolished by an antiserum against IGF I. Furthermore, IGF I was a factor of approximately 40 more potent than IGF II in stimulating erythroid colony formation. All of these findings suggest that the erythropoietic activity of FBS is IGF I.

Animals↗

Serum estradiols versus pelvic sonography in monitoring HMG therapy.

Therapy with human menopausal gonadotropin (HMG) conventionally has been monitored by estrogen measurements. Pelvic sonography may offer a more accurate method of monitoring HMG therapy. In this study 67 anovulatory patients were treated with HMG until at least one follicle had a diameter of 17 mm. The serum estradiol level was noted at the time a mature follicle was achieved. There was a correlation between the ultrasound data and the serum estradiol range in 57% of the cases. However, in 24% it was necessary to push the estradiol level above the allowable maximum of 2000 pg/mL. Twenty percent of the patients attained a 17-mm follicle before reaching the minimum required estradiol level of 500 pg/mL. Sonographic monitoring should improve the efficacy of HMG therapy.

Anovulation↗

The effect of insulin deprivation on fasting levels of 5000 dalton gastric inhibitory polypeptide in type 1 (insulin-dependent) diabetics.

To investigate whether metabolic decompensation has an effect on gastric inhibitory polypeptide (GIP), 8 fasting male type 1 diabetics were deprived of insulin for 12 h. An overnight insulin infusion aiming at normoglycaemia was stopped at 08.00 h. During the following 12 h blood glucose increased from 7.0 +/- 0.4 to 14.9 +/- 1.0 mmol/l, P less than 0.01, 3-hydroxy-butyrate from 0.18 +/- 0.07 to 4.00 +/- 0.74 nmol/1, P less than 0.01, and immunoreactive GIP (IR-GIP) from 16.7 +/- 2.6 to 21.9 +/- 2.9 pmol/1, P less than 0.05. The antiserum employed, R65, only measures 5000 dalton IR-GIP. The final IR-GIP concentrations were not significantly different from fasting IR-GIP concentrations in 13 normal male subjects (17.4 +/- 1.5 pmol/1). Short term insulin deprivation therefore is associated with a slight increase in fasting IR-GIP concentrations. Whether this modest increase in IR-GIP significantly enhances insulin secretion is unknown.

3-Hydroxybutyric Acid↗

Activation of phospholipase C and prostaglandin synthesis by [arginine]vasopressin in cultures.

[Arginine]vasopressin (AVP) stimulates maximal prostaglandin E2 production in cultured rat renal mesangial cells within 2 min. As early as 10s after addition of AVP (10(-6)M) a significant loss of radioactivity from phosphatidylinositol 4,5-bisphosphate but not from phosphatidylinositol 4-phosphate and phosphatidylinositol was observed in cells prelabelled with 32Pi. Cells labelled with [14C]arachidonic acid showed an increase of label in 1,2-diacylglycerol after 15 s and in phosphatidic acid after 30 s upon stimulation with AVP. Pretreatment of the cells with indomethacin (10(-5)M) did not abolish the effect of AVP on the increased labelling of phosphatidic acid.

Animals↗

Is renin secretion governed by the calcium permeability of the juxtaglomerular cell membrane?

Using cell cultures rich in renal juxtaglomerular cells we found that a change of the intracellular c-AMP concentration is not a prerequisite for an alteration of the renin secretion rate. Modulators of renin secretion including activators of the adenylate cyclase, however, altered the calcium permeability of the cellular plasma membrane in a way that stimulators of renin secretion lowered the calcium permeability and vice versa. Our results suggest that renin secretion is controlled by the intracellular calcium concentration and not by c-AMP. We postulate that modulators of renin secretion act by changing the calcium permeability of the cell membrane.

Angiotensin II↗

Pelvic sonography to help determine the appropriate therapy for luteal phase defects.

In some series the most appropriate therapy for luteal phase defects is supplemental progesterone in the luteal phase. Clomiphene's efficacy is more controversial since in one series only 8% achieved a successful pregnancy versus 45% in another study. Pelvic sonography was used to evaluate follicular development and release of the ovum in 50 infertile women with luteal phase defects. The results showed that only 40% had "pure" luteal phase defects whereas 52% had immature follicles and 8% had unruptured follicles. Sixty-two percent of the patients had previous therapy for a luteal phase defect and failed to conceive. Sixty-eight percent of this group did conceive when ultrasound was used to determine the appropriate therapy. Thus ultrasound can be employed to determine if the women with a luteal phase defect should be treated with a fertility drug, e.g., clomiphene or just with luteal phase progesterone support. Supplemental progesterone might still be needed with clomiphene based on repeat endometrial biopsy results.

Bromocriptine↗

Effects of fasting on the hypoxia-induced erythropoietin production in rats.

In order to test the hypothesis that the early cessation of erythropoietin (Ep) production during hypobaric hypoxia is induced by lowered food intake, we have compared the plasma Ep titer of rats after exposure to continuous hypoxia (42.6 kPa = 7000 m altitude) for 4 days with that in fed or fasted rats after exposure to discontinuous hypoxia. We found that plasma Ep was rather low after 4 days of continuous hypoxia. However, the Ep titer significantly rose again, when rats were maintained normoxic for 18 h and then exposed to repeated hypoxia for 6 h. Because this was also found in rats which were deprived of food during the normoxic interval and the second hypoxic period, we conclude that the fall of the Ep titer during continuous hypoxia is not primarily due to reduced food intake. In addition, our findings show that fasting per se lowers the Ep-response to hypoxia in normal rats but not exhypoxic rats.

Animals↗

Renal mesangial cell cultures as a model for study of erythropoietin production.

Mesangial cells derived from isolated glomeruli of rat kidney were grown as homogeneous cell lines in culture. They released, into the culture medium, erythropoietin that had free terminal galactosyl residues and was therefore not active in vivo. The production of erythropoietin by these cells was significantly enhanced by either lowering the PO2 in the incubation atmosphere or by adding cobalt chloride to the culture medium. Therefore, mesangial cells in culture may be considered as an in vitro system in which the regulation of erythropoietin production can be studied under well-defined conditions.

Animals↗

Extraction of erythropoietin from isolated renal glomeruli of hypoxic rats.

We investigated whether erythropoietin (Ep) can be extracted from renal glomeruli of hypoxic rats. Hypoxia was induced in a hypobaric chamber at 0.42 atmospheres for usually 6 h. Glomeruli were isolated with a sieving technique from kidneys that were flushed free of blood. Ep activities in glomeruli homogenates were determined in the fetal mouse liver cell assay and in the hypoxia exposed mouse assay. We found in vitro erythropoietic activity of glomerular extracts, which increased about 25-fold during hypoxia. Incubation of the extracts with anti-Ep serum abolished the activity. Its binding characteristics on Wheat germ lectin. Ricinus communis lectin and DEAE-cellulose suggested that glomeruli contained Ep precursor(s) that lacked terminal sugar residues. Such an incomplete carbohydrate portion seems also compatible with the finding that glomerular extracts did not stimulate erythropoiesis in hypoxia exposed mice.

Animals↗

A new candidate for the regulation of erythropoiesis. Insulin-like growth factor I.

The effect of pure human insulin-like growth factor I (IGF I) on the colony formation of late stage erythroid precursor cells (CFU-e) from fetal mouse liver and adult bone marrow was studied in a serum-free culture system. We found that IGF I in physiological concentrations stimulated erythroid colony formation. The combined effect of IGF I and erythropoietin was smaller than the sum of their single effects. The number of colonies induced by IGF I was linearly dependent on the number of plated cells. Our results indicate that IGF I is the first clearly defined mitogen that stimulates the late stages of erythroid differentiation independently of erythropoietin.

Animals↗