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Biomedical subjects

A Kurtz

Publications and source records attributed to A Kurtz.

At least 217 records · Page 12Linked to original sources
PubMed1989

[Regulation of erythropoietin synthesis].

The main regulatory hormone for the control of erythropoiesis is erythropoietin (EPO). This glycoprotein has a molecular weight of 34,000 daltons, about 40% of which is represented by carbohydrates. EPO leads to an enhanced mitosis and differentiation of erythroid precursors (colony-forming unit erythroid) in the bone marrow by binding to specific receptors. The major stimulus for EPO formation in the kidney is hypoxia. The tubular parts that are intimately involved in this O2-sensing mechanism are the proximal tubular cells as can be inferred from the use of site-specific transport inhibitors. The minimal time necessary for a hypoxic signal to induce EPO formation was found to be 30 min, including wash out of oxygen stores, activation of the EPO gene and equilibration of the EPO distribution space. About 1.5 h after the onset of hypoxia, EPO mRNA was found to accumulate in the kidney, thus pointing toward the possibility of an oxygen-regulated transcription or oxygen-dependent regulation of the stability of EPO mRNA. Possibly, a decrease in the intracellular calcium concentration is involved in this signalling process.

Animals↗
PubMed1989

[Assay methods for erythropoietin].

The aim of this contribution is to briefly characterize the assays available for the quantitation of erythropoietin (EPO). The radioimmunological determination of EPO has gained priority for routine and screening measurements. The in vivo bioassay is the most reliable assay for biologic EPO activity. In vitro bioassays should be limited to situations in which radioimmunoassays are not available and for which in vivo bioassays are too insensitive.

Animals↗
PubMed1989

[Erythropoiesis and serum erythropoietin concentrations before and after kidney allotransplantation].

Hematological parameters and serum erythropoietin (EPO) levels were measured before and sequentially after grafting in 50 consecutive cadaver renal transplant recipients. EPO was estimated using a sensitive radioimmunoassay. Values for nonanemic controls were 15-25 mU/ml. Mean hematological values before transplantation were as follows: hemoglobin 9.7 +/- 2.4 g/dl; hematocrit 29 +/- 8%; corrected reticulocytes count 15 +/- 8% and EPO 29 +/- 23 (11-131) mU/ml. In the entire studied population, 35 patients had inadequate low EPO levels for their degree of anemia. In the whole population, there was a significant positive exponential correlation between EPO and hematocrit (r = 0.31; p less than 0.05). In the subset of patients with underlying cystic kidney disease and in hemodialysis patients treated with recombinant human EPO, hemoglobin, hematocrit and EPO levels were higher when compared to hemodialysis or CAPD patients with other kidney diseases. Following successful renal transplantation, EPO increased to 45 +/- 31 mU/ml at 1 month and then decreased to 25 +/- 18, 18 +/- 7 and 19 +/- 4 mU/ml at 3,6 and 9 months, respectively. Within the 1st month after transplantation there was a 4-fold increase in reticulocytes from 9 +/- 5 to 38 +/- 14%, followed by a slow decrease over the next several months to 23 +/- 11% at 9 months. In contrast, the hematocrit level rose more gradually from 28 +/- 7 to 44 +/- 6% at 9 months. In 25 of 36 patients with a functioning graft who were followed for more than 6 months, anemia was corrected and 11 patients remained slightly anemic with a mean hematocrit level of 36 +/- 4%.

Erythropoiesis↗
PubMed1988

Evaluation of the stability of human erythropoietin in samples for radioimmunoassay.

Radioimmunoassays for erythropoietin are limited so far to a few specialized laboratories and this requires transport and storage of samples. We therefore tested the stability of immunoreactive erythropoietin in serum and plasma samples obtained from a uremic and a nonuremic anemic patient. No significant change in the concentration of immunoreactive erythropoietin was found in either serum or plasma samples for up to 14 days of storage. This type of stability was observed no matter whether the samples were stored at room temperature, 4 degrees C, or -20 degrees C. There was no difference between the estimates of erythropoietin in serum and heparinized plasma. Validity of the radioimmunoassay used in this study was demonstrated by parallelism of dilution curves of test specimens and the 2nd International Reference Preparation for erythropoietin and by a close correlation between the immunoreactivity and the bioactivity of the hormone, as assessed in the same samples by the exhypoxic polycythemic mouse bioassay. In conclusion the data obtained clearly indicate that the necessity of storage and transport of clinical samples does not limit the practicability of the radioimmunoassay for erythropoietin.

Anemia, Aplastic↗
PubMed1988

Role of cGMP as second messenger of adenosine in the inhibition of renin release.

Adenosine is known to be a potent inhibitor of renin release from the kidneys. The aim of this study was to investigate the transmembrane signalling avenue that the second messenger of adenosine causes inhibition of renal renin release. Using short term cultures of juxtaglomerular cells isolated from rat kidneys, we found that adenosine inhibited spontaneous renin release from these cells up to 40% of control, in a dose dependent fashion between 10(-10) M to 10(-6) M. Half maximal inhibition was observed at 2 X 10(-8) M adenosine. The inhibitory effect of adenosine on renin release could be mimicked by the A1-receptor agonist N6-cyclohexyladenosine (CHA) and could be attenuated by the A-receptor antagonist theophylline (5 X 10(-5) M). The A2-receptor agonist 5'-N-ethylcarboxamideadenosine (NECA) had no inhibitory effect on renin release. These findings indicate that the inhibitory effect of adenosine is mediated by A1-receptors on juxtaglomerular cells. Adenosine had no effect on either transmembrane calcium influx or the cytosolic free calcium concentration in the isolated juxtaglomerular cells. Adenosine also did not alter the cellular level of cyclic AMP in the concentration range employed. However, adenosine led to a dose dependent increase of the cellular level of cyclic GMP. Half maximal increase of cGMP was observed at 10(-8) M adenosine. The effect of adenosine on cyclic GMP could be mimicked by the A1-receptor agonist CHA and could be attenuated by the A-receptor antagonist, theophylline.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1988

Cyclosporine A enhances renin secretion and production in isolated juxtaglomerular cells.

Stimulation of the renin-angiotensin system is a major side effect of the fungoid immunosuppressant cyclosporine A (CyA). The aim of this study was to find out whether or not this effect of CyA results from a direct interaction with renal juxtaglomerular (JG) cells, which are the site of renal renin synthesis and release. Using primary cell cultures from rat renal cortex containing more than 80% JG cells, we found that CyA (0.01 to 10 micrograms/ml) stimulated renin secretion threefold. This stimulation was paralleled by a dose-dependent twofold increase of inactive renin within the cells, while the active intracellular renin remained the same. In order to identify a possible second messenger which could mediate the effects of CyA on JG cells, we examined the simultaneous effects of a single concentration of CyA (1 microgram/ml) on renin secretion, prostaglandin formation and intracellular cAMP concentration. However, prostaglandin formation and cAMP were not detectably altered by CyA in experiments where renin secretion was significantly enhanced. Our results indicate that cyclosporine A stimulates renin secretion and renin synthesis by a direct effect on renal juxtaglomerular cells. This action of CyA is not mediated by changes in cellular prostaglandin or intracellular cAMP.

Animals↗
PubMed1988

Insulin-like growth factor I stimulates erythropoiesis in hypophysectomized rats.

Stimulation of erythropoiesis during growth is necessary to ensure proportionality between erythrocyte mass and body mass. However, the way by which erythrocyte formation is adapted to body growth is still unknown. Growth arrest in hypophysectomized rats is accompanied by decreased erythropoiesis. We have, therefore, examined whether insulin-like growth factor I (IGF-I), the mediator of growth hormone effects on body growth, is able to restore erythropoiesis in these animals. Subcutaneous infusions of 120 micrograms of recombinant human IGF-I per day in hypophysectomized rats led to increases in body weight, 59Fe incorporation into erythrocytes, and the number of reticulocytes that were similar to increases caused by infusions of 28 milliunits of human growth hormone per day. Body weight gain and 59Fe incorporation were linearly correlated. Like growth hormone, IGF-I also caused a significant rise in serum erythropoietin concentrations. However, the stimulatory effect on erythropoiesis occurred before serum erythropoietin levels had risen. These results demonstrate that IGF-I mediates the stimulatory effect of growth hormone on erythropoiesis in vivo and thus further support the somatomedin concept. They also show that IGF-I can stimulate erythropoiesis in an endocrine manner, and they suggest two possible routes of action: a direct one and an indirect one by means of enhanced erythropoietin production.

Animals↗
PubMed1988

Rat juxtaglomerular cells are endowed with DA-1 dopamine receptors mediating renin release.

Under control conditions a primary culture containing about 80-90% of granular juxtaglomerular (JG) cells prepared from rat kidneys continuously released renin into the culture medium at a rate of 17.9 +/- 1.4 ng angiotensin I/h per mg of cell proteins per 30 min (n = 14). Dopamine (1.0 microM), the DA-1 dopamine receptor agonist fenoldopam (0.5 microM), and isoproterenol (1.0 microM) increased renin secretion markedly (130-200%). Propranolol (0.1 microM) reduced the effects of isoproterenol significantly (80%), but not those of dopamine or fenoldopam. In contrast, SCH 23390 (0.01 microM), a DA-1 dopamine receptor antagonist, inhibited markedly only the renin release evoked by the latter two agonists, whereas S-sulpiride (10 microM), a DA-2 dopamine receptor antagonist, and phentolamine (10 microM), a nonselective alpha-adrenoceptor antagonist, did not modify the effects of either dopamine or fenoldopam. In rats, pithed to eliminate reflexogenic mechanisms regulating renin release, at the end of a 15 min i.v. infusion of fenoldopam (20 micrograms/kg per min) there was a significant increase in plasma renin activity. This effect was completely prevented by SCH 23390 (0.1 mg/kg i.v.) but not significantly changed by S-sulpiride (0.3 mg/kg i.v.) or phentolamine (3.0 mg/kg i.v.) plus propranolol (0.75 mg/kg i.v.). In conclusion, these results indicate that DA-1 dopamine receptors are present in rat kidney JG cells and that pharmacological stimulation of these receptors with dopamine or fenoldopam leads to renin secretion.

Animals↗
PubMed1988

Calcitonin gene-related peptide is a stimulator of renin secretion.

Calcitonin gene-related peptide (CGRP) was found to stimulate renin secretion in vivo in normal human volunteers. Moreover, CGRP stimulated the release of renin in vitro from isolated rat renal juxtaglomerular cells (half-maximal effective concentration [EC50] 100 nM) concomitant with stimulation of cAMP production (EC50 60 nM). Immunoreactive CGRP was recognized in rat renal cortical nerve fibers, and intact rat CGRP was identified in extracts of the rat renal cortex. Because CGRP containing sensory nerve fibers are seen in the region of the juxtaglomerular apparatus, it would seem that the release of CGRP from these afferent nerves may be involved in the physiological control of renin secretion.

Animals↗
PubMed1988

CT diagnosis of circumcaval ureter.

Variability in the normal course of the ureter makes it difficult to differentiate a normal variant from a congenital anomaly or deviation caused by a mass. CT can be useful in making this distinction. We present five cases of circumcaval ureter in which contrast-enhanced CT, by showing the ureter passing posterior and medial to the inferior vena cava (IVC), provided the definitive diagnosis. In addition, we studied the position of the inferior vena cava in the midlumbar region in 100 consecutive contrast-enhanced CT scans and compared the results with the position of the IVC in our five cases of circumcaval ureter plus one case of circumcaval ureter taken from the literature. Whereas only 6% of the normal patients had an IVC lateral to the right pedicle of the third lumbar vertebra, all of the patients with a circumcaval ureter and the one case in the literature had the IVC lateral to the pedicle. Therefore, the finding of a laterally placed IVC on CT is suggestive but not pathognomonic of circumcaval ureter. Contrast-enhanced CT can be used to prove the diagnosis of circumcaval ureter, and lateral placement of the IVC on non-contrast-enhanced CT suggests the diagnosis.

Adult↗
PubMed1988

[Amnesic syndrome caused by infarction in the area of the left anterior choroidal artery].

A case of infarction in the left anterior choroidal artery territory presenting as a regressive amnestic syndrome, associated with the usual syndrome, is reported. This amnesia had the same characteristics as that found in the left posterior cerebral artery territory infarction. The anterior choroidal artery supplies the medial part of the temporal lobe, the amygdaloid nucleus, part of the hippocampus, uncal gyrus, and the mamillary body. Therefore, an amnestic syndrome can occur together with an infarction in the AChA territory. To our knowledge this is the first report of that occurrence.

Aged↗
PubMed1987

Identification of a polypeptide growth inhibitor from bovine mammary gland. Sequence homology to fatty acid- and retinoid-binding proteins.

A polypeptide growth inhibitor purified from bovine mammary gland (mammary-derived growth inhibitor) has been shown to reversibly inhibit proliferation of mammary carcinoma cells at concentrations of about 10(-10) M. The carrier of inhibitory activity has been identified biochemically as an about 13-kDa polypeptide and chemically by elucidating the amino acid sequence. No homology to any of the hitherto structurally investigated growth inhibitors (transforming growth factor beta, interferons) has been observed. The data revealed extensive sequence homology of mammary-derived growth inhibitor to a family of low molecular mass hydrophobic ligand-binding proteins, among them a fatty acid-binding protein from rat heart, myelin P2, a differentiation associated protein in adipocytes (p422) and the cellular retinoic acid-binding protein. Interaction with as yet unknown hydrophobic ligands might play a functional role in the mechanism of growth inhibition excerted by mammary-derived growth inhibitor.

Animals↗
PubMed1987

Cyclosporin A inhibits PGE2 release from vascular smooth muscle cells.

The influence of the fungoid undecapeptide cyclosporin A (CyA) on PGE2 release from cultured rat aortic smooth muscle cells was investigated in this study. We found that CyA time and concentration dependently (ED50:500 ng/ml) inhibited PGE2 release from the cells. CyA attenuated both basal and PGE2 release evoked by angiotensin II (10(-10)-10(-6) M), arginine vasopressin (10(-10)-10(-6) M) and ionomycin (10(-9)-10(-6) M). CyA (1 microgram/ml) did not affect the conversion of exogenous arachidonic acid (1 microM) into PGE2. The inhibitory effect of CyA was neutralized by high concentrations of the calcium ionophore ionomycin (greater than 3 X 10(-6) M). Taken together our results indicate that CyA inhibits both basal and vasoconstrictor evoked PGE2 release from vascular smooth muscle by impairing the availability of free arachidonic acid rather than by inhibiting the conversion of arachidonic acid into PGE2.

Angiotensin II↗
PubMed1987

Adenosine stimulates guanylate cyclase activity in vascular smooth muscle cells.

Good evidence exists to indicate that the vasodilating effect of adenosine is mediated by cell surface receptors on vascular smooth muscle cells. The mechanism of transmembrane signal transduction for adenosine, however, is not fully understood. Since cGMP is a second messenger known to mediate vasodilation, I have examined the effect of adenosine on the intracellular concentration of cGMP in vascular smooth muscle cells from rat aorta. I found that adenosine at 10(-9) to 10(-5) M led to an increase in intracellular cGMP levels in a dose-dependent fashion. The effect of adenosine on cyclic guanosine inorganic monophosphate (cGMP) could be mimicked by the A-type receptor agonists N6-cyclohexyladenosine and 5'-N-ethylcarboxamidoadenosine and was attenuated by the A-receptor antagonist theophylline. The order of potency of the adenosine analogues was N6-cyclohexyladenosine greater than 5'-N-ethylcarboxamidoadenosine greater than adenosine. These findings suggest that the effect of adenosine on cGMPi is mediated by A1-type cell surface receptors. Concerning the mechanism by which adenosine could elevate cGMPi, I found that the effect of adenosine on cGMPi was potentiated by the cGMP phosphodiesterase-specific inhibitor M & B 22948. Moreover, I found that N6-cyclohexyladenosine, 5'-N-ethylcarboxamidoadenosine, and adenosine stimulated a guanylate cyclase in homogenates of the cultured smooth muscle cells in a dose-dependent fashion with the same order of potency as their effects on cGMPi. Further evidence was obtained to indicate that adenosine and its analogues stimulated a particulate guanylate cyclase activity, whereas they did not alter soluble guanylate cyclase activity. Since cGMP is known as a second messenger mediating relaxation of vascular smooth muscle cells, the results obtained in this study could suggest that adenosine exerts its vasorelaxing effect by activating an Ai-receptor-linked guanylate cyclase.

Adenosine↗