Biomedical subjects

W Rascher

Publications and source records attributed to W Rascher.

At least 145 records · Page 8Linked to original sources

PubMed1994

Atrial natriuretic peptide and cyclic guanosine-monophosphate in children and adolescents on peritoneal dialysis.

Plasma concentrations of atrial natriuretic peptide (ANP) and its second messenger cyclic guanosine-monophosphate (cGMP) were studied in 28 children and adolescents (1 to 19 years) on peritoneal dialysis and compared to 55 healthy children (1 to 20 years). Dialysate concentrations of the hormones were measured also in the patients. Plasma ANP was not significantly different in patients and controls (28.8 pmol/l [15.5-53.6 pmol/l] [median, lower and upper quartile] versus 26.3 pmol/l [19.9-31.8 pmol/l]). In seven children on peritoneal dialysis it exceeded an upper normal limit of 50 pmol/l, but it fell to normal values in four of them after forced fluid withdrawal. Plasma cGMP was elevated in the patients compared to the control children (1.6 nmol/l [1.1-1.7 nmol/l] versus 1.0 nmol/l [0.8-1.2 nmol/l]; p < 0.05). There were only weak correlations between plasma and dialysate concentrations of ANP and cGMP. Plasma concentrations of ANP seem to be elevated in children on peritoneal dialysis in case of fluid overload.

Adolescent↗

PubMed1994

Elevated plasma concentration of neuropeptide Y in adolescents with primary hypertension.

Neuropeptide Y (NPY) has been recently characterised as a circulating vasoconstrictor peptide which is co-stored with noradrenaline (NA) in sympathetic neurons. We measured NPY by radioimmunoassay and NA by HPLC in plasma of ten healthy volunteers (23-27 years of age) during bicycle ergometry and found a rapid increase of both NPY and NA during exercise. NPY rose from 1.3 +/- 0.5 to 9.6 +/- 7.8 pmol/l and NA from 1.3 +/- 0.3 to 10.8 +/- 5.6 mnol/l (mean +/- SD). Following maximal exercise NA disappeared more rapidly from plasma than NPY. Compared with these healthy volunteers, plasma NPY was found to be elevated in 23 children and adolescents aged 9-18 years with borderline primary hypertension (NPY 3.1 +/- 1.7 pmol/l, P < 0.01). Basal NPY was also elevated when compared with 21 age-matched pediatric controls (P < 0.05). The bicycle ergometry protocol performed in 23 patients separated ten adolescents with normal basal and exercise blood pressure from 13 with high BP also during ergometry. In the latter group, NPY rose to 11.9 +/- 7.3 pmol/l and NA to 12.3 +/- 8.6 nmol/l during exercise. Treatment of the hypertensive patients with the beta-adrenergic blocker atenolol (50 mg per day) lowered basal and exercise BP. Heart rate fell during atenolol treatment from 92 +/- 19 to 72 +/- 15 beats/min. Treatment did not alter plasma concentrations under basal conditions and during exercise (NPY from 2.8 +/- 2.1 to 11.7 +/- 5.3 pmol/l and NA from 2.0 +/- 0.8 to 15.6 +/- 14.1 nmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1994

Elevated urinary excretion of endothelin-like immunoreactivity in children with renal disease is related to urine flow rate.

Endothelin 1-21 belongs to a family of locally produced regulatory peptides with potent vasoconstrictor activity and profound renal effects. To study the biological significance of endothelin in children with renal diseases, we measured urinary endothelin-like immunoreactivity (ETir) excretion in children and adolescents (60 normal controls and 57 patients with renal disease). ETir excretion was constant during childhood and adolescence (4-18 years). Compared to these normal controls elevated urinary excretions of ETir were found in children with chronic renal failure, following renal transplantation and with idiopathic hypercalciuria (all groups p < 0.001). However, ETir excretion was unchanged in children with idiopathic steroid sensitive nephrotic syndrome, with stable chronic glomerulonephritis and in 4 patients with hemolytic uremic syndrome. Urinary ETir concentrations were similar in controls and in various patient groups. ETir excretion correlated positively with urine flow rate in normal controls (r = 0.71) and in all patients studied (r = 0.91). Fractional excretion of ETir correlated negatively with glomerular filtration rate. Eight healthy volunteers (23-27 years old, 4 female, 4 male) were studied before and after oral water load (20 ml/kg) to investigated the effect of ETir excretion on urine flow rate. Urine flow rose tenfold in response to water load and urine concentration of ETir fell only by factor 3 and urinary ETir excretion rose fivefold. These results indicate that urinary ETir excretion is related to and depends at least in part on urine flow rate. ETir excretion may so reflect a role of ETir in renal disease, especially in the diuretic state.

Adolescent↗

PubMed1993

Identification of four novel mutations in the COL4A5 gene of patients with Alport syndrome.

The type IV collagen alpha 5 chain (COL4A5) genes of patients with Alport syndrome were tested for major gene rearrangements by Southern blot analysis, using COL4A5 cDNA clones as probes. In addition, individual exons were screened for small mutations by single-strand conformation polymorphism (SSCP) analysis. Four new COL4A5 mutations were detected. A duplication of the nine most 3' located nucleotides of exon 49 and the first nucleotide of intron 49 was identified in the COL4A5 gene of one patient. Two patients displayed single base substitutions leading to, respectively, a proline to threonine and an arginine to glutamine substitution in the C-terminal end. Both substitutions involve amino acids conserved through evolution. In COL4A5 intron 41 a mutation changing the splice acceptor site from AG to AA was identified. All mutations cosegregate with the clinical phenotype of Alport syndrome in affected family members. In a control population of 50 individuals tested by PCR-SSCP these mutations were never identified. Together with two mutations reported previously, a total of six mutations were found in 26 patients with Alport syndrome (23%) after systematic screening of about 30% of the COL4A5 coding region. The clinical features of these six patients are described in detail.

Amino Acid Sequence↗

PubMed1993

Urinary endothelin excretion in the neonate: influence of maturity and perinatal pathology.

The present study was undertaken to establish the developmental pattern of urinary endothelin-1 (ET-1) excretion and to define its possible role in mediating pathophysiological changes related to perinatal asphyxia/infection and dopamine treatment. Urinary ET-1 levels were measured by radioimmunoassay in 7 full-term neonates (mean gestational age 39.3 weeks) on days 1, 3 and 5, and in 9 pre-term neonates (mean gestational age 30.8 weeks) on days 1, 3, 5, 7 and weekly thereafter for 5 consecutive weeks. The results were compared with those of three age-groups of 30 normal children (4-8 years, 9-12 years and 13-18 years); each group consisted of 10 children. The influence of severe cardiopulmonary distress (n = 16, mean gestational age 33.9 weeks, post-natal age 3.3 days) and dopamine administration in a dose of 2 micrograms/min per kg (n = 10, mean gestational and post-natal ages 32.1 weeks and 5.6 days, respectively) were also studied. In full-term infants, ET-1 concentration fell from 34.3 +/- 1.8 pmol/l on day 1 to 21.5 +/- 1.5 pmol/l on day 5 (P < 0.01). In premature infants its absolute value and its post-natal fall were similar in the 1st week and no further change occurred in weeks 2-5; it stabilized at levels between 17.1 +/- 2.2 and 16.7 +/- 1.7 pmol/l. These concentrations tended to be lower than those of 25.5 +/- 1.3, 23.0 +/- 1.0 and 26.2 +/- 0.7 pmol/l measured in three groups of older children.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1993

Clinical settings and vasopressin function in hyponatraemic children.

Hyponatraemia is one of the most common electrolyte abnormalities in hospitalised children. In a prospective study we tested whether hyponatraemia is associated with sustained release of the antidiuretic hormone arginine vasopressin (AVP). Out of 27 children with persistent hyponatremia (serum sodium < 130 mmol/l), 25 had measurable plasma concentrations of AVP [median and quartiles 5.0 pg/ml (1.5-8.3)]. Volume contraction as consequence of sodium loss caused hyponatraemia in 16 patients. Hyponatraemia in the presence of extracellular volume expansion and reduced effective arterial blood volume occurred in 5 patients. Only 3 patients had normovolaemic hyponatraemia (so-called syndrome of inappropriate antidiuretic hormone secretion) and 3 suffered from chronic renal failure. It is concluded that plasma AVP concentration is measurable in most children with hyponatraemia. Non-osmotic stimulation of AVP release and lack of suppression of this hormone is an important pathogenetic mechanism of hyponatraemia in children.

Adolescent↗

PubMed1993

Involvement of the central nervous system in renal hypertension.

Involvement of the central nervous system (CNS) is a major complication of renal hypertension and is usually due to hypertensive encephalopathy. During a 17-year period we observed 25 children with renal hypertension associated with CNS manifestations in the absence of (group A) and 33 in the presence of advanced renal failure (group B). Convulsions were the most important symptom (65% in both groups combined). Other manifestations were reduced consciousness (69%), visual disturbances (28%), hemiplegia (14%), and cranial nerve palsy (10%). In 56% of children in group A, hypertension was recognised only after appearance of CNS symptoms. Three patients in group A and 19 in group B died. Intracranial haemorrhage associated with hemiplegia was found in 3 cases. From 1970-1977 to 1978-1986 the number of patients and the mortality in group B declined dramatically, probably as a result of improved antihypertensive and renal replacement therapy. In contrast, in group A the number of patients and of CNS symptoms remained similar. The study underlines the importance of frequent blood pressure monitoring in presence of acute or chronic renal disease.

Adolescent↗

PubMed1993

Is PP56 (D-myo-inositol-1,2,6-trisphosphate) an antagonist at neuropeptide Y receptors?

PP56 (D-myo-inositol-1,2,6,-trisphosphate) has been reported to specifically inhibit neuropeptide Y-mediated effects in vasculature, heart and brain; because of its reversible but non-competitive antagonism interaction with neuropeptide Y receptor signalling or allosteric modulation of neuropeptide Y binding have been postulated. These possibilities were tested in the present study. PP56 did not affect [125I]neuropeptide Y binding to HEL- or SK-N-MC-cells or to porcine splenic membranes. PP56 did not inhibit neuropeptide Y-stimulated Ca2+ increases in HEL- or SK-N-MC-cells or in cultured porcine aortic vascular smooth muscle cells but if anything slightly enhanced it. PP56 did not antagonize the neuropeptide Y-mediated inhibition of forskolin-stimulated cAMP accumulation in HEL-cells. We conclude that previously reported antagonistic effects of PP56 occur distal to the neuropeptide Y receptor or its second messenger systems Ca2+ and cAMP or may be restricted to neuropeptide Y receptors in certain model systems.

Animals↗

PubMed1993

Serial measurements of neuropeptide Y in plasma for monitoring neuroblastoma in children.

Neuropeptide Y (NPY) was studied as a marker for neuroblastoma in 12 children. All but one patient with neuroblastoma had elevated plasma NPY concentrations at diagnosis. During treatment NPY values returned to normal in 9 of 12 children. All three children without normalization of plasma NPY values died; two of them had a relapse and the third died of toxic effects. Plasma NPY appears to be a sensitive marker of neuroblastoma.

Adolescent↗

PubMed1993

Primary obstructed megaureter in neonates. Treatment by temporary uretero-cutaneostomy.

During the last 10 years we have treated 24 newborn and young infants (27 ureters) in whom the diagnosis of primary obstructed megaureter was established by diuresis-enhanced radionuclide renography and/or by antegrade pressure flow studies (Whitaker test). Temporary uretero-cutaneostomy was performed immediately after diagnosis. After 1 year a second modified Whitaker test showed normal passage of the contrast medium into the bladder in 23 ureters. In only 4 ureters did obstruction persist and uretero-cystoneostomy was performed. Ureterocystoneostomy was also performed on 8 ureters without obstruction but with persistent vesicoureteric reflux, ectopic ureter or diverticula. In 11 patients a temporary uretero-cutaneostomy was closed without corrective surgery at the vesicoureteric junction. Temporary uretero-cutaneostomy is a safe and effective therapy in primary obstructed megaureter in newborns. Spontaneous relief of obstruction appears to be possible in primary obstructed megaureter.

Dermatologic Surgical Procedures↗

PubMed1993

Atrial natriuretic peptide in dumping syndrome.

The significance of atrial natriuretic peptide (ANP) was investigated in the maintenance of the fluid volume in hypovolemia associated with dumping syndrome following gastric resection. The study was performed on 10 patients who had undergone a Billroth II procedure. Ten age- and sex-matched patients without previous gastric surgery served as control. Each patient underwent an oral glucose challenge. The patients with gastric resection underwent another glucose challenge with intravenous infusion to maintain the fluid volume. All patients with gastric resection showed subjective symptoms of the early dumping syndrome with significant (p < 0.001) increases (initial and maximum rates; mean +/- SD) in heart rate (from 70 +/- 3 to 122 +/- 4 beats/min) and in hematocrit (from 0.40 +/- 0.005 to 0.45 +/- 0.003). The plasma ANP level decreased significantly from 27.24 +/- 5.01 to 15.94 +/- 3.61 fmol/ml (p < 0.01). A significant negative correlation was found between the changes in hematocrit and the changes in plasma ANP level (r = 0.68; p < 0.001). Neither the subjective symptoms characteristic of the early dumping syndrome nor changes in laboratory parameters were noted in the patients during the challenge with infusion. The results show that the hypovolemia in dumping syndrome is associated with a significant decrease in ANP activity. The regulation of ANP release is also affected: apart from the well-known stimulating effect of hypervolemia, there exists an inhibition of secretion in volume-depleted states.

Atrial Natriuretic Factor↗

PubMed1993

Influence of NaCl supplementation on vasopressin secretion and water excretion in premature infants.

The study was carried out to assess the possible involvement of excess AVP and free water retention in the development of late hyponatremia by comparing the postnatal course of plasma AVP and urinary excretion of AVP and sodium as well as creatinine, osmolar and free water clearances in premature infants with (group S) and without (group NS) NaCl supplementation. Plasma total protein and albumin concentrations were also determined. Group NS consisted of 8 infants with a birth weight of 1,150-1,730 g (mean: 1,440 g) and gestational age of 28-32 weeks (mean: 30.4 weeks). Group S included 8 infants with a mean birth weight of 1,390 g (range: 980-1,700 g) and a mean gestational age of 30.1 weeks (range: 27-32 weeks). Measurements were made on the 7th day and weekly thereafter until the 5th week of life. NaCl supplementation was given in a dose of 3-5 and 1.5-2.5 mmol/kg/day for 8-21 and 22-35 days, respectively. Infants receiving sodium supplements had significantly greater urinary sodium excretion (p < 0.01), retained more sodium (p < 0.01), maintained plasma sodium at normal levels and gained weight at slightly higher rates when compared with those on low sodium. Plasma AVP tended to be higher in group S but did not differ significantly from that in NS group. Urinary AVP excretion, however, either expressed in ng/day or ng/100 ml GFR, was significantly higher in group S, although the age-related increase could not be seen when correction was made for GFR.(ABSTRACT TRUNCATED AT 250 WORDS)

Arginine Vasopressin↗

PubMed1993

Angiotensin II-induced vasopressin release is mediated through alpha-1 adrenoceptors and angiotensin II AT1 receptors in the supraoptic nucleus.

The central actions of angiotensin II (ANG II) include the release of vasopressin (AVP) from the supraoptic nucleus (SON) via the pituitary gland into the blood. In conscious rats, we investigated whether catecholamines in the SON are involved in this release process. It was found that i.c.v. injections of ANG II (100 ng) selectively increased the release of norepinephrine (NA) from the SON. Like the ANG II i.c.v.-induced AVP release, this effect was prevented by i.c.v. pretreatment with the ANG II AT1 receptor antagonist, losartan (5 micrograms). The alpha-1 adrenoceptor antagonist, prazosin (0.7 nmol), injected bilaterally into the SON, significantly reduced the ANG II 100-ng i.c.v.-induced AVP release. Pretreatment with the alpha-2, beta-1 and beta-2 adrenoceptor antagonists, idazoxan, atenolol and ICI 118551, respectively, had no effect. Injections of NA into the SON increased plasma AVP at doses up to 10 nmol but not at higher doses (30-100 nmol). The effects of NA were mimicked by the alpha-1 adrenoceptor agonist, methoxamine (1-5 nmol). Bilateral pretreatment of the SON with losartan (5 micrograms) markedly inhibited the i.c.v. ANG II 100 ng-induced AVP release. The increase in AVP release after ANG II injections into the SON was also inhibited by losartan pretreatment into the SON, whereas prazosin had no effect. These results demonstrate that the ANG II-induced release of AVP is initiated through periventricular ANG II AT1 receptors and involves postsynaptic alpha-1 adrenoceptor stimulation in the SON. In addition, ANG II AT1 receptors in the SON can contribute to AVP release after periventricular ANG II receptor stimulation.

Adrenergic alpha-1 Receptor Antagonists↗

PubMed1992

Novel generation of hormone receptor specificity by amino terminal processing of peptide YY.

The physiological significance of multiple Y receptors has not been determined since until recently only one form of endogenous agonists was known, namely PYY1-36 and NPY1-36. Recently, a new molecular form of PYY was characterized as des(Tyr-Pro)PYY (PYY3-36 or PYY-II). Its ability to interact at various Y receptors was not characterized. Analytical chromatography of fresh canine colon extracts shows two peaks of immunoreactivity eluting in the positions of PYY-II and PYY1-36 (PYY). PYY-II was about 40% of the total PYY immunoreactivity indicating that it is one of the major forms of PYY expressing its biological activity. It is shown that PYY-II will not displace label from the Y1 receptors found on a human neuroblastoma cell line. It is further shown that PYY-II is as potent as PYY for the inhibition of pancreatic secretion, which must occur through Y2 receptors. The enzymatic removal of Tyr-Pro from PYY to form PYY-II must therefore regulate the relative expression of a non-selective agonist (PYY) to a highly selective Y2 agonist (PYY-II). Amino terminal processing of PYY represents a novel type of regulation of peptide hormone specificity. It has important biological implications for PYY and potential relevance for other peptide hormone receptor systems.

Animals↗

PubMed1992

NPY and carbachol raise Ca2+ in SK-N-MC cells by three different mechanisms. Evidence for inositol phosphate-independent Ca2+ mobilization by NPY.

We have compared the mechanism of NPY- and carbachol-stimulated Ca2+ increases in SK-N-MC cells. NPY stimulated Ca2+ mobilization via a pertussis toxin-sensitive mechanism. Carbachol stimulated Ca2+ mobilization and influx via pertussis toxin-insensitive and -sensitive mechanisms, respectively. Carbachol but not NPY stimulated inositol phosphate accumulation by a pertussis toxin-insensitive mechanism. We conclude that carbachol promotes Ca2+ influx via a pertussis toxin-sensitive G protein and Ca2+ mobilization via a pertussis toxin-insensitive G-protein coupling to inositol phosphate generation; NPY stimulates Ca2+ mobilization via a pertussis toxin-sensitive G protein without apparent involvement of inositol phosphates.

Calcium↗

PubMed1992

Atrial natriuretic peptide and cyclic 3'5'-guanosine monophosphate as indicators of fluid volume overload in children with chronic renal failure.

Plasma atrial natriuretic peptide (ANP) and cyclic 3'5'-guanosine monophosphate (cGMP) were investigated as indicators of fluid volume overload in children and adolescents with chronic renal failure. Plasma ANP and cGMP were measured in both paediatric patients with chronic renal failure (n = 17, mean serum creatinine 371 +/- 242 mumol/l) and those with end-stage renal disease on haemodialysis (n = 18). cGMP was higher in children with chronic renal failure than in 45 healthy controls (1.0 +/- 0.4 vs 2.1 +/- 0.8 nmol/l, P less than 0.01), whereas plasma ANP was similar (26.9 +/- 9.7 vs 34.0 +/- 12.3 pmol/l). Both ANP and cGMP were markedly elevated in children with end-stage renal disease before haemodialysis and fell significantly during dialysis. During dialysis body weight decreased by 1.6 +/- 0.7 kg, corresponding to 4.5 +/- 2.1% of body weight. Plasma ANP correlated positively with plasma cGMP in haemodialysed patients (r = 0.43, P less than 0.05). Reduction in body weight and in mean arterial pressure correlated more closely with plasma ANP than with cGMP. Therefore, elevation of plasma ANP appears to indicate volume overload in children undergoing haemodialysis, but whether it can be used also in children with chronic renal failure requires further investigation.

Adolescent↗

PubMed1992

Neuropeptide Y (NPY) receptors in HEL cells: comparison of binding and functional parameters for full and partial agonists and a non-peptide antagonist.

1. We have compared the binding and Ca2+ mobilizing properties of various full agonists, partial agonists and a non-peptide antagonist at the neuropeptide Y (NPY) receptor of human erythroleukemia (HEL) cells. 2. [125I]-NPY binding to intact HEL cells was rapid, saturable, of high affinity and with a specificity typical for the Y1-like subtype: NPY, peptide YY (PYY) and [Pro34]-NPY competed for [125I]-NPY binding with high affinity whereas NPY13-36 and NPY18-36 had only low affinity. 3. NPY, PYY and [Pro34]-NPY potently increased intracellular Ca2+ in HEL cells and had equal efficacy. NPY13-36, vasoactive intestinal peptide (VIP) and pancreatic polypeptide (PP) increased intracellular Ca2+ only poorly. 4. Whereas VIP and PP did not significantly affect NPY-stimulated Ca2+ mobilization, NPY13-36 inhibited NPY-stimulated Ca2+ increases and shifted the NPY concentration-response curve to the right without altering its maximal effect. 5. The agonist (pEC50) potencies of the various peptides corresponded well with the affinities of these compounds in the binding assay (pKi), whereas the antagonist potencies (pKb) of the peptide partial agonists and the pA2 value of the non-peptide NPY antagonist (He 90481), calculated from functional data, were lower than the respective affinities determined in the binding studies. 6. A plot of the fractional Ca2+ response vs the fractional receptor occupancy did not reveal any non-linear receptor-effector coupling for NPY or [Pro34]-NPY; a small receptor reserve might exist for PYY. 7. We conclude that the binding and functional properties of HEL cell NPY receptors are very similar. NPY, PYY and [Pro34]NPY are full agonists at these receptors, whereas NPY13-36 is a partial agonist.

Calcium↗

PubMed1992

NPY-stimulated Ca2+ mobilization in SK-N-MC cells is enhanced after isoproterenol treatment.

Neuropeptide Y (NPY) receptors in the SK-N-MC human neuroblastoma cell line couple to mobilization of intracellular Ca2+ and inhibition of adenylylcyclase. Pretreatment of SK-N-MC cells with isoproterenol enhanced the NPY-stimulated Ca2+ mobilization, mainly by increasing the maximal response to NPY. The enhancement was time-(maximal after 24 h) and concentration-dependent (maximal at 10 microM isoproterenol), blocked by the beta-adrenergic antagonist propranolol, and mimicked by forskolin. Concomitant treatment with cycloheximide prevented the enhancing effect of isoproterenol, suggesting the involvement of protein synthesis. Isoproterenol treatment did not alter the number or affinity of 125I-labeled NPY binding sites, the amount of pertussis toxin substrates, or NPY-mediated inhibition of cAMP accumulation. Similarly, isoproterenol treatment had no effect on basal intracellular Ca2+ and on Ca2+ increases elicited by carbachol, caffeine, or ionomycin. We conclude that isoproterenol treatment can sensitize NPY receptor responsiveness in a way that is specific for Ca2+ mobilization mechanisms used by this hormone.

Adenylyl Cyclases↗