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A Kurtz

Publications and source records attributed to A Kurtz.

At least 163 records · Page 9Linked to original sources
PubMed1993

Effect of endothelium-derived relaxing factor on renin secretion from isolated mouse renal juxtaglomerular cells.

This study aimed to examine the direct influence of native endothelium derived relaxing factor (EDRF) on renin secretion. To this end isolated mouse renal juxtaglomerular cells were cocultured with bovine aortic endothelial cells which produced and released significant amounts of EDRF as assayed by guanylate cyclase activities which were measured separately in endothelial and juxtaglomerular cells as well as in the cocultures of juxtaglomerular with endothelial cells. EDRF production was blunted in the absence of extracellular L-arginine and in the presence of N omega-nitro-L-arginine (L-NAG; 200 microM). Inhibition of endothelial EDRF production by removal of arginine or addition of L-NAG was associated with a significant decrease of renin secretion from the cocultures while the same regimen had no effect on renin secretion from JG cells alone. Exogenous generation of nitric oxide by the addition of sodium nitroprusside (100 microM) stimulated renin secretion in the cocultures both at normal and inhibited EDRF formation as well as from juxtaglomerular cells alone. These findings suggest that native EDRF released from vascular endothelial cells is a stimulatory signal for renin secretion from renal juxtaglomerular cells.

Animals↗
PubMed1993

Interrelation between baroreceptor and macula densa mechanisms in the control of renin secretion.

1. It was the aim of this study to examine the interrelation between 'baroreceptor' function and the macula densa signal in the control of renin secretion from the kidneys. To this end we investigated the effects of frusemide and bumetanide, two different inhibitors of the macula densa Na(+)-K(+)-2Cl- cotransport, on pressure-dependent renin release from isolated perfused rat kidneys. In addition, pressure modulation of renin secretion from hydronephrotic kidneys devoid of macula densa structures was examined. 2. Basal flow rate through isolated kidneys was 13.5 +/- 1.0 ml min-1 g-1 at a renal artery pressure of 100 mmHg and corresponding renin secretory rates were 5.5 +/- 0.5 (ng angiotensin I (Ang I) h-1) min-1 g-1 (mean +/- S.E.M., n = 15). 3. Frusemide (10-100 microM) and bumetanide (5-50 microM) increased urine flow rates and stimulated urinary sodium excretion in a dose-dependent fashion from 13.0 +/- 2.5 mumol min-1 g-1 (n = 10) under control conditions to maximal values of 38.0 +/- 5.0 (n = 5) and 37.0 +/- 2.0 mumol min-1 g-1 (n = 5), respectively. Both drugs also induced concentration-dependent decreases of the renal vascular resistance. The vasorelaxant effects of frusemide and bumetanide were paralleled by an increase of renin secretion to a maximum of 21 +/- 4 (ng Ang I h-1) min-1 g-1 (n = 10). On a molar basis bumetanide was twice as potent as frusemide in stimulating renin secretion. 4. Lowering of the perfusion pressure from 100 to 40 mmHg resulted in a prompt increase of renin release yielding secretion rates of 92 +/- 10 (ng Ang I h-1) min-1 g-1 (n = 15). In the presence of frusemide (100 microM) and bumetanide (50 microM) renin secretion rates at 40 mmHg were 97 +/- 11 and 133 +/- 24 (ng Ang I h-1) min-1 g-1 (n = 6), respectively. Renin release stimulated by bumetanide was significantly reduced to 8.0 +/- 1.5 (ng Ang I h-1) min-1 g-1 (n = 5) by elevating the perfusion pressure from 100 to 140 mmHg. 5. Lowering the renal artery pressure from 100 to 40 mmHg in isolated perfused rat hydronephrotic kidneys devoid of tubular structures increased renin secretion rates from 4.5 +/- 1.0 to 22.5 +/- 2.5 (ng Ang I h-1) min-1 (n = 5).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Liberators of NO exert a dual effect on renin secretion from isolated mouse renal juxtaglomerular cells.

This study aimed to examine the role of nitric oxide (NO) in the regulation of renin secretion from renal juxtaglomerular (JG) cells. Using primary cultures of mouse renal JG cells, we found that sodium nitroprusside (SNP) and 3-morpholino-sydnonimin-hydrochloride (SIN-1), two structurally different liberators of NO, led to a transient inhibition during the first hour followed by a marked dose-dependent stimulation of renin secretion lasting for an additional 20 h. This stimulatory effect was blunted by methylene blue (50 microM) and was reversible within minutes after removal of the NO liberators. SNP and SIN-1 also stimulated guanylate cyclase activity in the cultures with a maximum within the first hour of incubation. Increasing intracellular guanosine 3',5'-cyclic monophosphate levels by 8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphate (100 microM) or by atrial natriuretic peptide (10 nM) decreased basal renin secretion but did not inhibit the effect of SNP. The stimulatory effect of SNP was not related to adenosine 3',5'-cyclic monophosphate levels in the JG cells and was blunted after chelation of extracellular calcium by 2 mM ethylene glycol-bis(beta-amino-ethyl ether)-N,N,N'N'-tetraacetic acid. Taken together, our findings suggest that liberators of NO have two effects on renin secretion from isolated JG cells: an inhibitory effect mediated by stimulation of soluble guanylate cyclase activity and a stimulatory effect mediated by an as yet unknown pathway that requires extracellular calcium.

Animals↗
PubMed1993

Renin mRNA quantification using polymerase chain reaction in cultured juxtaglomerular cells. Short-term effects of cAMP on renin mRNA and secretion.

The aim of the present study was to set up a method to quantify renin mRNA levels in mouse renal juxtaglomerular cells, the main physiological site of renin synthesis. Because of the scarcity of the cells, a quantitative polymerase chain reaction had to be developed to measure renin mRNA. Juxtaglomerular cells were isolated and cultured for 2 days under various conditions, and renin mRNA was measured directly from the cytoplasm of the cultured cells without prior RNA purification. An internal standard consisting of a mutated renin mRNA with an insertion of 60 bp was designed to quantify the reaction, ensuring an identical detection and amplification efficiency to the target RNA. Renin mRNA could be precisely quantified between 0.6 and 20 pg, thus allowing its detection in approximately 5000 juxtaglomerular cells. Forskolin, an activator of adenylate cyclase, led to a concentration-dependent maximal threefold increase in renin mRNA in the cultures after 20 hours of incubation. The half-maximal effective dose was 3 x 10(-7) mol/L. The effect of forskolin was mimicked by 10(-5) mol/L isoproterenol, a beta-receptor agonist, and by 10(-5) mol/L isobutylmethylxanthine. A time-course study showed a rapid increase in renin mRNA within 3 hours after forskolin and isoproterenol addition. Renin secretion in the culture medium was measured in parallel and found to be stimulated by both agents. These results show that quantitative polymerase chain reaction is a suitable tool for studying renin gene expression in cultured juxtaglomerular cells. Our findings indicate that cAMP is a potent and fast activator of renin gene transcription and renin secretion in renal juxtaglomerular cells.

1-Methyl-3-isobutylxanthine↗
PubMed1993

Increased plasma viscosity as a reason for inappropriate erythropoietin formation.

The aim of this study was to examine whether altered plasma viscosity could contribute to the inappropriately low production rate of erythropoietin (EPO) observed in patients suffering from hypergammaglobulinemias associated with multiple myeloma or Waldenström's disease. We found that the EPO formation in response to anemia in these patients was inversely related to plasma viscosity. A similar inverse relationship between plasma viscosity and EPO production was seen in rats in which EPO formation had been stimulated by exchange transfusion and the plasma viscosity of which was thereby altered by using exchange solutions of different composition to alter plasma viscosity and thus whole blood viscosity independently from hematocrit. Raising the gammaglobulin concentration to approximately 40 mg/ml plasma in the rats almost totally blunted the rise in serum EPO levels despite a fall of the hematocrit to 20%. Determination of renal EPO mRNA levels by RNase protection revealed that the reductions in serum EPO levels at higher plasma viscosities were paralleled by reductions in renal EPO mRNA levels. Taken together, our findings suggest that plasma viscosity may be a significant inhibitory modulator of anemia-induced EPO formation. The increased plasma viscosity in patients with hypergammaglobulinemias may therefore contribute to the inappropriate EPO production, which is a major reason for the anemia developing in these patients.

Adult↗
PubMed1993

Involvement of endothelium-derived relaxing factor in the pressure control of renin secretion from isolated perfused kidney.

Using isolated rat kidneys perfused at controlled pressure, we examined a potential role of endothelium-derived relaxing factor (EDRF) in the pressure control of renin secretion. We found that stimulation of EDRF release by acetylcholine (1 mumol/liter) increased mean perfusate flow rates from 15.0 +/- 0.5 to 18.0 +/- 0.5 ml/min per g and average renin secretion rates from 3.5 +/- 0.5 to 16.0 +/- 2.0 ng angiotensin I/h per min per g at a perfusion pressure of 100 mmHg (mean +/- SEM, n = 6). Those effects of acetylcholine were significantly reduced during inhibition of EDRF formation with NG-nitro-L-arginine (100 mumol/liter), but they were not affected with the cyclooxygenase inhibitor indomethacin (10 mumol/liter). Lowering of the perfusion pressure from 100 mmHg to 40 mmHg resulted in an increase of average renin secretion rates from 3.5 +/- 0.5 to 79 +/- 12 ng AngI/h per min per g under control conditions (n = 8), and to 171 +/- 20 ng AngI/h per min per g in the presence of 10 mumol/liter acetylcholine (n = 3). The rise of renin secretion in response to a reduction of the renal artery pressure was markedly attenuated with inhibitors of EDRF formation such as NG-nitro-L-arginine (100 mumol/liter) and related compounds. During inhibition of EDRF formation, addition of sodium nitroprusside (10 mumol/liter) increased mean perfusate flow rates from 12.0 +/- 0.5 to 23.0 +/- 2.0 ml/min per g and average renin secretion rates from 2.0 +/- 0.5 to 18.0 +/- 1.5 ng AngI/h per min per g at 100 mmHg (n = 5). Lowering of the perfusion pressure from 100 mmHg to 40 mmHg under those conditions increased average renin secretion rates to 220 +/- 14 ng AngI/h per min per g (n = 5). Taken together, our findings suggest that EDRF and related activators of soluble guanylate cyclase stimulate renin secretion from isolated kidneys, predominantly at lower perfusion pressure. Moreover, pressure control of renin secretion appears to require the tonical stimulation by intrarenal EDRF.

Acetylcholine↗
PubMed1993

Disseminated intravascular coagulation with leukemia patients.

Disseminated intravascular coagulation (DIC) is a perplexing syndrome that involves both clot formation and bleeding. The management of this syndrome for leukemia patients is especially difficult because of the abnormal coagulation parameters already present in this population. The purpose of this article is to describe normal blood coagulation physiology and the pathophysiology of DIC, and identify appropriate nursing diagnoses and interventions for the leukemia patient with DIC.

Adult↗
PubMed1992

Disparate effects of calcium channel blockers on pressure dependence of renin secretion and flow in the isolated perfused rat kidney.

Using the model of isolated perfused rat kidneys this study was performed to investigate whether or not voltage-operated calcium channels are essentially involved in the pressure control of renin secretion from the kidneys. At a perfusion pressure of 100 mm Hg (13.3 kPa) renin secretory rates were 4.2 +/- 0.7 (ng angiotensin I h-1) min-1 g-1. Stepwise reduction of renal perfusion pressure to 80, 60, and 40 mm Hg (10.6, 8.0, 5.3 kPa) resulted in an increase of renin release yielding a 30-fold stimulation at 40 mm Hg vs 100 mm Hg. Increasing the perfusion pressure above 100 mm Hg did not further significantly decrease renin secretion. The perfusate flow rate was also pressure-dependent. Flow rates increased linearly with pressure and reached a plateau at 100 mm Hg, which was maintained up to 160 mm Hg (21.3 kPa). The averaged flow rate at the plateau was 15.5 ml min-1 g-1. In the presence of the three different calcium antagonists nifedipine (5 microM), nitrendipine (3 microM) and verapamil (5 microM), myogenic autoregulation of flow was abolished as indicated by the rise of the pressure/flow curve between 40 and 160 mm Hg. At the same time, however, these calcium channel blockers did not alter the relationship between perfusion pressure and renin secretion. Moreover, the calcium channel agonist Bay K 8644 (5 microM) caused a strong and long-lasting vasoconstriction, without changing renin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1992

Identification and localization of microsatellite markers covering human chromosome 18.

To generate microsatellite markers from chromosome 18, we have cytogenetically localized a large number of lambda phage using a deletion mapping panel of somatic cell hybrids. Here we describe the identification of 65 new CA-repeat-containing phage and the localization of five markers developed in other laboratories. This approach allows the selection of a subset of markers that are well spaced across the chromosome and can be developed as genetic markers. The use of PCR-based markers should allow for the rapid genomic screening of disease genes on chromosome 18.

Base Sequence↗
PubMed1992

Contribution of fine needle aspiration cytology to diagnosis and management of thyroid disease.

AIMS: To determine the role of fine needle aspiration cytology (FNAC) in the diagnosis and management of thyroid disease. METHODS: Clinical histories of 144 patients who had undergone FNAC of the thyroid were analysed. Clinical presentation, non-invasive investigations including hormone assays, ultrasound, and isotope scan procedures were compared with FNAC diagnoses in all cases and with histological diagnosis in the 28 cases (19%) that had undergone surgery. Clinical management was decided upon combining all of the above investigations. The relative contribution of the FNAC was divided into: essential, additional and non-contributory, misleading. RESULTS: FNAC diagnoses included: 29 (16%) benign colloid goitre, 56 (39%) benign cystic goitre, 24 (17%) thyroiditis, and 22 (15%) neoplasms. Nineteen (13%) of the specimens were unsatisfactory. When compared with clinical diagnoses based on non-invasive diagnostic investigations FNAC represented no improvement on the diagnosis of benign colloid/cystic goitre (55% v 54% respectively). It represented an improvement on the diagnosis of thyroiditis (9% v 17% respectively). FNAC decreased clinically suspicious lesions in which 22 neoplasms were diagnosed from 37% to 15%. Eleven patients with neoplasms underwent surgery and neoplasms were confirmed histologically. Others including lymphoma, metastatic carcinoma, and analplastic carcinoma were managed conservatively. There were four false negative FNAC diagnoses (3%) in clinically suspicious lesions, found on histology to be benign follicular adenomas. CONCLUSIONS: FNAC had an essential role in the diagnosis and management of 23% of our patients, a confirmatory role in 61% of patients, a non-contributory role in 13% when specimens were inadequate, and was misleading in 3% where results were false negative. The positive identification of thyroiditis and neoplasia stands on its own as a justification for FNAC.

Adolescent↗
PubMed1992

Phorbol ester inhibits erythropoietin production in human hepatoma cells (Hep G2).

Using the human hepatoma cell line Hep G2, we have studied a possible role of protein kinase C (PKC) activity for regulation of erythropoietin (EPO) production. During a 72-h incubation, EPO production by the cells was stimulated sevenfold by exposure to low oxygen tension (1%) and threefold by exposure to cobaltous chloride (100 microM). The phorbol ester phorbol 12-myristate-13 acetate (PMA) led to a concentration-dependent inhibition of basal and stimulated EPO formation (ED50 10 nM). This decrease of EPO production, which was apparent already after 1 h of incubation with PMA, reached its maximal effect after 24 h and held on for 72 h. It was paralleled by an inhibition of the increase of EPO mRNA levels in response to stimulation. A 24-h preincubation of the cells with PMA (100 nM) virtually blunted the effect of hypoxia on EPO formation. Recovery of EPO synthesis after removal of PMA took 48-72 h. The effect of PMA on EPO production was mimicked by phorbol 12,13-dibutyrate (ED50 1 microM) but not by 4 alpha-phorbol 12,13-didecanoate. The synthetic diacylglycerol analogues oleolyl-acetylglycerol and dioctanoylglycerol (2-200 microM) also had no effect on either basal or stimulated EPO production. Treatment with PMA caused a translocation of the alpha-isoenzyme of PKC from the cytosol to the membrane after 1 h and a disappearance of the membrane-bound form after 24 h of incubation. Staurosporine and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, two structurally different inhibitors of PKC activity, inhibited basal and stimulated EPO production with ED50 values of 9 nM and 50 microM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1992

Insulin-like growth factors decrease oxygen-regulated erythropoietin production by human hepatoma cells (Hep G2).

We examined the effects of insulin-like growth factors (IGFs) and insulin on erythropoietin (EPO) production by human hepatoma cells (Hep G2). Compared with normoxia (20% O2), EPO production by Hep G2 cells during a 72-h incubation was stimulated fivefold by exposure to low oxygen tension (1% O2) and nearly threefold by exposure to cobalt chloride (100 microM). IGF-I caused a concentration-dependent attenuation of EPO formation under normoxic conditions and inhibited (maximally 50%) EPO production stimulated by either low oxygen tension or cobalt [half-maximal effect (ED50) approximately 5 nM]. The increase of EPO mRNA levels in response to hypoxia was significantly reduced by IGF-I. Similarly to IGF-I, IGF-II (ED50 approximately 8 nM) and insulin (ED50 approximately 80 nM) also inhibited EPO formation in Hep G2 cells. IGF-I (100 pM-100 nM) stimulated the incorporation of radiolabeled alanine as a measure for total protein synthesis, 3H-labeled thymidine incorporation into DNA, and glycogen synthesis at 20 and 1% O2 in a concentration-dependent fashion. IGF-I exhibited a high affinity for the IGF-I receptor (apparent Kd approximately 3 nM). Unlabeled insulin was greater than 100-fold less potent than IGF-I in competing for 125I-IGF-I binding (apparent Kd approximately 360 nM). Conversely, insulin bound to the insulin receptor with high affinity (apparent Kd approximately 0.3 nM), whereas IGF-I was less than 1% as potent in competing for 125I-insulin binding. In summary, IGFs and insulin exert a negative control function on oxygen-regulated EPO production in Hep G2 cells. The inhibitory effect of IGFs and insulin on EPO formation appears to be mediated via the IGF-I receptor.

Animals↗
PubMed1992

Calmodulin antagonists stimulate renin secretion and inhibit renin synthesis in vitro.

To find out whether calmodulin activity could be a common denominator for the cellular control of renin secretion and synthesis, we have examined the effects of calmodulin antagonists on the secretion and the synthesis of renin in primary cultures of mouse juxtaglomerular (JG) cells. We found that the calmodulin antagonists calmidazolium (CMDZ), N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide (W-7), and trifluoperazine (TFP) strongly stimulated renin release from isolated JG cells with a rank order of potency CMDZ greater than TFP greater than W-7. With the same order of potency as on renin secretion, CMDZ, TFP, and W-7 also inhibited de novo synthesis of renin. This decrease of renin synthesis went in parallel with a general inhibition of protein synthesis in the cultured JG cells. A comparable inhibition of total protein synthesis and renin synthesis as with CMDZ was achieved with cycloheximide. Cycloheximide, however, did not alter renin secretion within 20 h of incubation. Taken together, our findings suggest that inhibition of calmodulin activity exerts a powerful stimulatory effect on the exocytosis of renin in renal JG cells. Calmodulin activity on the other hand is also essentially required for protein and renin synthesis in JG cells. It is not very likely therefore that calmodulin activity positively links renin synthesis and renin secretion in JG cells.

Animals↗
PubMed1992

Renal innervation plays no role in oxygen-dependent control of erythropoietin mRNA levels.

To assess the role of renal innervation in O2-dependent control of erythropoietin (EPO) formation, we have determined EPO mRNA levels in both kidneys of unilaterally denervated rats and sham-operated controls using RNase protection. To investigate whether possible effects of renal nerve input are related to the type of hypoxic stimulus and the degree of stimulation, animals were studied under basal conditions, after exposure to normobaric hypoxia (8% O2, 4 h) or CO (0.1%, 4 h), and after acute hemorrhage (decrease in hematocrit from 40.8 +/- 0.5 to 12.7 +/- 0.5% within 7 h; mean +/- SE, n = 6). Serum EPO levels rose on average 22-, 49-, and 48-fold under the three stimuli and were unaffected by unilateral denervation. Renal EPO mRNA levels in unilaterally denervated animals, when expressed in arbitrary units revealed by comparison with an external standard, were 7.0 +/- 1.5 vs. 6.3 +/- 2.0 (normoxia), 432 +/- 136 vs. 451 +/- 156 (normobaric hypoxia), 971 +/- 93 vs. 930 +/- 120 (CO), and 604 +/- 170 vs. 689 +/- 203 (hemorrhagic anemia) in the intact vs. the denervated kidney (mean +/- SE, n = 3). Furthermore, there was no difference between EPO mRNA levels of either kidney of unilaterally denervated animals and levels in sham-operated controls. We conclude that renal nerve input plays no significant role in the control of the EPO gene under both basal and stimulated conditions.

Anemia↗
PubMed1992

Age-dependent expression of the erythropoietin gene in rat liver and kidneys.

Using RNAse protection, we have made quantitative measurements of erythropoietin (EPO) mRNA in liver and kidneys of developing rats (days 1-54), to determine the relative contribution of both organs to the total EPO mRNA, to monitor changes which occur with development, and to compare the hypoxia-induced accumulation of EPO mRNA with the changes in serum EPO concentrations. To determine whether developmental and organ-specific responsiveness is related to the type of hypoxic stimulus, normobaric hypoxia was compared with exposure to carbon monoxide (functional anemia). Under both stimuli EPO mRNA concentration in liver was maximal on day 7 and declined during development. In contrast, EPO mRNA concentration in kidney increased during development from day 1 when it was 30-65% the hepatic concentration to day 54 when it was 12-fold higher than in liver. When organ weight was considered the liver was found to contain the majority of EPO mRNA in the first three to four weeks of life, and although, in stimulated animals, the hepatic proportion declined from 85-91% on day 1, it remained approximately 33% at day 54 and was similar for the two types of stimuli. When normalized for body weight the sum of renal and hepatic EPO mRNA in animals of a particular age was related linearly to serum hormone concentrations. However, the slope of this regression increased progressively with development, suggesting age-dependent alterations in translational efficiency or EPO metabolism.

Age Factors↗