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Biomedical subjects

W Rascher

Publications and source records attributed to W Rascher.

At least 127 records · Page 7Linked to original sources
PubMed1996

Insulin and cortisol promote leptin production in cultured human fat cells.

The aim of this study was to investigate the regulation of leptin expression and production in cultured human adipocytes using the model of in vitro differentiated human adipocytes. Freshly isolated human preadipocytes did not exhibit significant leptin mRNA and protein levels as assessed by reverse transcriptase (RT)-polymerase chain reaction (PCR) and radioimmunoassay (RIA). However, during differentiation induced by a defined adipogenic serum-free medium, cellular leptin mRNA and leptin protein released into the medium increased considerably in accordance with the cellular lipid accumulation. In fully differentiated human fat cells, insulin provoked a dose-dependent rise in leptin protein. Cortisol at a near physiological concentration of 10(-8) mol/l was found to potentiate this insulin effect by almost threefold. Removal of insulin and cortisol, respectively, was followed by a rapid decrease in leptin expression, which was reversible after readdition of the hormones. These results clearly indicate that both insulin and cortisol are potent and possibly physiological regulators of leptin expression in human adipose tissue.

Adipose Tissue↗
PubMed1996

[Cryptorchism--assessment from an andrologic viewpoint].

This report deals with the pathology, diagnosis and therapy of cryptorchidism from the andrological point of view. Hypothalamic-pituitary gonadal failure and a reduced transformation of gonocytes are the key factors in fertility disorders. The aim of all well-timed therapy must be to improve the fertility potential of the sexually mature male. At present, the determination through biopsy of the fertility index during orchiopexy offers the only possibility of prospective diagnosis in this respect. In the future, it will be necessary to have a standardized procedure in order to guarantee the long-term effect of correctly timed orchiopexy on fertility.

Adolescent↗
PubMed1996

Automated blood pressure measurement in children.

Techniques to measure blood pressure are even more complicated in children and particularly in infants as in adults, since appropriate cuff sizes and special reference values are necessary. In pediatric patients oscillometry is the automated method of choice and is in use since more than 15 years (Dinamap). Recently, ambulatory blood pressure measurement (ABPM) with an oscillometric device (SpaceLabs) has become a valuable too in the diagnosis and therapeutic monitoring of arterial hypertension of children and adolescents. Normal casual blood pressure measurements have been studied in large studies demonstrating an increase of systolic and diastolic blood pressure with age, or even more with body height. These reference values are not applicable to evaluate ABPM. Recent studies in single centers as well as a multicenter study (of 1141 participants) have provided pediatric reference values for ABPM. Daytime mean systolic blood pressure increased with height from 111 to 120 mm Hg in girls (body height 120 to 180 cm) as well as in boys from 112 to 124 mm Hg. However, daytime mean diastolic blood pressure did not change during maturation and was 72 to 74 mm Hg irrespective of height and sex. The upper normal values (95th percentile) were 13-15 mm Hg above the mean. Since there is a striking difference between normal casual blood pressure and normal ABPM in children, it is essential to use appropriate blood pressure references.

Adolescent↗
PubMed1995

Does the overexpression of pro-insulin-like growth factor-II in transfected human embryonic kidney fibroblasts increase the secretion of lysosomal enzymes?

Insulin-like growth factor-II (IGF-II) and lysosomal enzymes bearing the mannose 6-phosphate (Man6P) recognition marker, bind to two distinct binding sites of the IGF-II/M6P receptor. The two classes of ligands reciprocally modulate the binding of the other class of ligand to the receptor [Kiess, W., Thomas, C. L., Greenstein, L., Lee, L., Sklar, M. M., Rechler, M. M., Sahagian, G. G. & Nissley, S. P. (1989) J. Biol. Chem. 264, 4710-4714]. We asked whether or not overexpression of pro-IGF-II by cells in culture leads to missorting of lysosomal enzymes. Human embryonal kidney fibroblasts were transfected with the full-length human IGF-II cDNA or a control cDNA. Solution hybridization/RNase protection experiments using a human IGF-II riboprobe showed that two transfectants expressed large quantities of IGF-II mRNA, whereas the non-transfected cells did not. The analysis of conditioned media revealed that these cells secrete approximately 0.15 micrograms and 1.0 micrograms immunoreactive IGF-II/ml and 22 x 10(6) cells and 24 x 10(6) cells within 24 hours. Immunoreactive IGF-II was shown by Western blotting to represent 17-kDa pro-IGF-II. The amount of the lysosomal enzyme, beta-hexosaminidase, was approximately twofold increased in the conditioned media from pro-IGF-II overexpressing cells compared with control media, as shown by Western-blot analysis and immunoprecipitation of media extracts of metabolically labeled cells. The synthesis rate of beta-hexosaminidase was not affected by pro-IGF-II overexpression. In addition, the basal amount of another newly synthesized lysosomal enzyme, the cathepsin D precursor, was also twofold higher in pro-IGF-II overexpressing cells than in control cells. In contrast, the surface binding and cellular uptake rate of a Man6P-containing neoglycoprotein did not differ between the cell lines. The results indicate that the overexpression of pro-IGF-II doubles the secretion and/or reduces the re-uptake of beta-hexosaminidase and cathepsin D to approximately 20% of the total synthesized enzymes in human embryonal kidney fibroblasts compared to control cells. We hypothesize that, in cells synthesizing high amounts of pro-IGF-II, the growth factor may modulate the targeting of a portion of lysosomal enzymes, mainly by partially enhancing the secretion of newly synthesized enzymes and, in addition, possibly by affecting the re-uptake mechanism.

Cathepsin D↗
PubMed1995

Angiotensin AT1 receptor-mediated vasopressin release and drinking are potentiated by an AT2 receptor antagonist.

Stimulation of angiotensin II AT2 receptors has been shown to inhibit AT1 receptor-mediated actions in peripheral tissues. The role of AT2 receptors in the central actions of angiotensin is not well understood. In the present study, plasma vasopressin levels and water intake in response to intracerebroventricular angiotensin II (10 pmol) were determined after intracerebroventricular pretreatment with PD 123177 (1-(4-amino-3-methylphenyl)methyl-5-diphenylacetyl-4,5,6,7-tetrahy dro-1H- imidazo[4,5-c]pyridine-6-carboxylic acid-2HCl), a selective AT2 receptor antagonist (10, 100 and 1000 pmol), or with losartan (2-n-butyl-4-chloro-5-hydroxy-methyl-1-2'-(1H-tetrazole-5-yl)biphenyl-4- yl)methylimidazole, potassium salt), a specific AT1 receptor antagonist (0.2, 2 and 10 nmol). Blood samples for vasopressin determination were drawn 90 s after angiotensin II injection and the drinking response was determined in a time interval of 10 min after intracerebroventricular angiotensin II. Losartan at a dose of 2 nmol or higher completely prevented vasopressin release and drinking response to angiotensin II. The drinking response was already attenuated after pretreatment with the lowest dose of losartan. In contrast, PD 123177 potentiated the angiotensin II-induced vasopressin release (39.7 +/- 2.7 pg/ml after 1000 pmol PD 123177 vs. 21.3 +/- 2.9 pg/ml in vehicle-pretreated controls, P < 0.05). The dipsogenic response to angiotensin II was also potentiated by PD 123177 (9.5 +/- 0.7 ml after 1000 pmol PD 123177 vs. 5.1 +/- 1.3 ml in vehicle-pretreated controls, P < 0.05). Our results suggest that the angiotensin II-induced vasopressin release and drinking, mediated by central AT1 receptors, are under inhibitory control by central AT2 receptors.

Angiotensin II↗
PubMed1995

Hyponatraemia and hyperkalaemia in acute pyelonephritis without urinary tract anomalies.

UNLABELLED: Three children with severe hyponatraemia and hyperkalaemia associated with acute pyelonephritis are reported. All were very young male infants in a poor general condition and seriously dehydrated. Diagnostic procedures did not detect obstructive uropathy or vesico-ureteric reflux. CONCLUSION: Hyponatraemia and hyperkalaemia occurs in young infants with severe acute pyelonephritis in the absence of obstructive uropathy or vesico-ureteric reflux. The severe inflammation of the kidney itself may explain the electrolyte disturbance by a transient resistance of the distal tubule to aldosterone.

Acute Disease↗
PubMed1995

Urinary excretion of aldosterone, arginine vasopressin and cortisol in premature infants with maximum renal acid stimulation.

Of 452 low-birth-weight infants who were routinely screened for maximum renal acid stimulation (MRAS) (urine pH < 5.4), 149 episodes of incipient late metabolic acidosis (urine pH < 5.4 on 2 consecutive days) were randomly allocated to either a control group or treatment with NaHCO3 or NaCl (2 mmol/kg/day each) for 7 days. Urinary excretion of aldosterone-18-glucuronide (Aldo), arginine vasopressin (AVP) and cortisol was determined in timed urine samples. On day 1, patients with MRAS showed a tendency towards increased urinary excretion of Aldo compared with infants without MRAS. In patients who received alkali therapy, urinary excretion of Aldo, AVP and cortisol decreased or showed a trend to lower values from day 1 to day 7, whereas in patients with MRAS but no specific therapy, Aldo and AVP showed a tendency to increase. We concluded that persistent MRAS is not only characterized by a reduced rate of weight gain and a tendency to decreased nitrogen assimilation, but also increased secretion of Aldo and AVP.

Acidosis↗
PubMed1995

Regulation of NPY/NPY Y1 receptor/G protein system in rat brain cortex.

Neuropeptide Y (NPY) content, NPY receptors, and alpha-subunits of the G proteins Go and Gi were determined in cerebral cortex of male normotensive Wistar-Kyoto and spontaneously hypertensive rats at 3-28 wk of age and of adult female rats. NPY lacked major effects on adenylate cyclase or inositol phosphate formation. NPY content was similar in all normotensive groups but lower in spontaneously hypertensive rats at all ages. 125I-NPY labeled a homogeneous population of Y1-like receptors. The Y1 NPY receptor number gradually increased with age with similar values in both strains but was significantly smaller in female than in male rats. The Y1 NPY receptor affinity was similar in all male groups but greater in female rats. The abundance of immunodetectable Go alpha and Gi alpha and of pertussis toxin substrates was less at 3 wk than in older rats but similar in both sexes and strains. We conclude that rat cerebral cortex contains Y1-like receptors; sex, age, and blood pressure differentially regulate NPY content, Y1 NPY receptors, and Go alpha and Gi alpha.

Adenylate Cyclase Toxin↗
PubMed1995

Neuropeptide Y: a possible role in hypertension?

PURPOSE: To evaluate whether neuropeptide Y (NPY) is likely to be relevant as a regulator of cardiovascular function in general and of blood pressure control in arterial hypertension in particular, based on a literature survey. RESULTS OF DATA ANALYSIS: NPY is a putative cotransmitter of many central and peripheral sympathetic neurons. It and its receptors are present in brain areas and peripheral tissues involved in cardiovascular regulation, and administration of exogenous NPY to these sites can elicit functional cardiovascular responses by acting on specific pre- and postsynaptic receptors. Moreover, NPY may act as a growth factor for the development of vascular and cardiac hypertrophy. The release of NPY and postsynaptic vasoconstriction responses to NPY may be enhanced in hypertension, whereas presynaptic inhibitory responses may be attenuated. Some of these alterations may precede the development of blood pressure elevations in the spontaneously hypertensive rat model of genetic hypertension. CONCLUSIONS: NPY might be an important physiological and pathophysiological modulator of cardiovascular function, but further studies using specific high-affinity antagonists are required.

Animals↗
PubMed1995

Failure of arginine-vasopressin and other pressor hormones to increase in severe recurrent dialysis hypotension.

BACKGROUND: Recurrent dialysis hypotension is common in long-term dialysis patients. Arginine-vasopressin (AVP) is a potent vasoconstrictor hormone, release of which is stimulated in hypotension. STUDY DESIGN: We measured AVP as well as adrenaline and noradrenaline in 23 patients with recurrent dialysis hypotension during severe symptomatic episodes of dialysis hypotension (BP syst. < 70 mmHg). We also tested autonomic function (amyl nitrate inhalation, cold pressor test) during the interdialytic interval. RESULTS: We observed that systolic blood pressure decreased from 127 +/- 8 (at the end of the first hour of dialysis; taken as control state) to 64 +/- 1 mmHg (symptomatic hypotension) in 23 patients. In six of the 23 patients hypotension was accompanied by nausea, which is a known direct stimulus of AVP. In these six patients, plasma AVP showed a large increase: control state, 6.2 +/- 0.9; hypotension, 130.4 +/- 51.1 pg/ml; P < 0.5). Of the remaining 17 patients without nausea, AVP fell moderately in nine and increased in eight. Taken together, this group of 17 hypotensive patients failed to show significant AVP stimulation: control state, 9.0 +/- 1.4; hypotension, 13.8 +/- 3.8 pg/ml, NS). Adrenaline and noradrenaline did not change during hypotension. During autonomic testing the patients with recurrent dialysis hypotension (compared to healthy controls) showed blunted baroreflex response (assessed by amyl nitrate inhalation) but intact sympathetic outflow (assessed by cold pressor test). CONCLUSION: The observations of AVP are taken as further evidence of defects in the afferent rather than the efferent limb of autonomic reflexes in dialysis patients with recurrent dialysis hypotension.

Acute Disease↗
PubMed1994

Two novel mutations in the vasopressin V2 receptor gene in patients with congenital nephrogenic diabetes insipidus.

Families with congenital nephrogenic diabetes insipidus were analyzed with regard to mutations in the vasopressin V2 receptor gene. Family 1 shows an X-chromosomal recessive inheritance of the disease over 4 generations. A patient from this family was found to have a T-->A transversion at nucleotide 1095, predictive for a substitution of serine 167 (which is highly conserved among G-protein-coupled receptors), by threonine. Both the mutant and the normal allele were detected in the maternal genome. The patient's healthy brother was homozygous for the normal allele. The patient from family 2 showed a T-->C transition at nucleotide 727, predictive for a substitution of leucine 44 by proline. Analysis of the maternal genome revealed homozygosity for the normal allele. Thus a de novo mutation seems to have occurred. The nature and site of the mutation in family 2 suggest that it is responsible for the patient's disease.

Amino Acid Sequence↗
PubMed1994

[Pro34]peptide YY is a Y1-selective agonist at peptide YY/neuropeptide Y receptors.

We have investigated binding and functional effects of a new peptide YY analogue, [Pro34]peptide YY, at Y1 and Y2-like subtypes of receptors for peptide YY and neuropeptide Y. In binding studies [Pro34]peptide YY had a similarly high affinity as peptide YY to human Y1-like receptors in SK-N-MC cells, a human neuroblastoma cell line of presumed neurogenic origin, and HEL cells, a human cell line derived from a patient with Hodgkin's disease. In functional studies [Pro34]peptide YY stimulated Ca2+ elevations in both Y1-like receptor cell lines with similar potency and efficacy as peptide YY. In contrast to peptide YY [Pro34]peptide YY was 1000-fold less potent in binding to Y2-like receptors in porcine splenic membranes and lacked agonistic effects in another Y2-like receptor-mediated model system, i.e. inhibition of [3H]serotonin release from rat cerebral cortical slices. Thus, [Pro34]peptide YY is a highly Y1-selective full agonist of peptide YY/neuropeptide Y receptors. [Pro34]peptide YY could be useful for studying the importance of Y receptor subtypes in mediating peptide YY physiological actions.

Amino Acid Sequence↗
PubMed1994

Renal electrolyte and water handling in normal pregnancy: possible role of endothelin-1.

The study was carried out to determine the urinary excretion of endothelin-1 (ET-1) in normal pregnancy and to define its possible role in mediating the renal response to aldosterone and arginine vasopressin (AVP). Measurements were performed in 12 healthy pregnant women serially in the 20th, 24th, 28th, 32nd and 36th weeks of pregnancy. Urinary ET-1, plasma and urinary aldosterone and AVP levels (RIA methods) as well as plasma and urine sodium, potassium, creatinine and osmolality were measured; creatinine clearance (Ccr), osmolar clearance (Cosm) and free water clearance (CH2O) calculated. Fractional sodium excretion (FENa), urine sodium/potassium ratio (Na/K) and transtubular potassium concentration gradient (TTKG) were also determined. It was demonstrated that urinary ET-1 excretion was higher in pregnant than in non-pregnant women and it increased further as the pregnancy progressed from 34.8 +/- 4.0 pmol/day in week 20 to 44.1 +/- 3.2 pmol/day in week 36 (P < 0.01). Daily ET-1 excretion significantly correlated with AVP (r = 0.39, P < 0.005) and aldosterone excretion (r = 0.62, P < 0.0001). Furthermore, there was a significant positive relationship between ET-1 excretion and urine flow rate (r = 0.67, P < 0.0001), CCR (r = 0.40, P < 0.0025), Cosm (r = 0.58, P < 0.001), sodium (r = 0.56, P < 0.001) and potassium excretion (r = 0.42, P < 0.001). However, such a relationship could not be established between ET-1 excretion and FENa, TTKG and Na/K.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Effect of sodium chloride supplementation on urinary endothelin-1 excretion in premature infants.

We investigated the role of endothelin-1 in the renal adaptation to alterations in sodium balance in premature infants. The postnatal course of urinary endothelin-1 excretion, an estimate of renal endothelin-1 production, was compared in premature infants receiving low or high sodium intake. Sodium supplementation was given in a dose of 3 to 5 mmol/kg per day and 1.5 to 2.5 mmol/kg per day at the postnatal ages of 8 to 21 and 22 to 35 days, respectively. Sodium balance and urinary endothelin-1 excretion were determined weekly up to the fifth week of life. Urinary endothelin-1 concentration (expressed in picomoles per liter) and urinary endothelin-1 excretion (expressed either in terms of picomoles per square meter per day or picomoles per millimole creatinine) were significantly lower in infants receiving a high sodium intake compared with those receiving low sodium intake (p < 0.001) in weeks 2 through 5. We conclude that in sodium-depleted premature infants with high urinary sodium excretion, an angiotensin II-mediated increase in renal endothelin-1 production occurs, which acts in concert with angiotensin II to restore sodium balance.

Endothelins↗
PubMed1994

Differentiation of glomerular and non-glomerular hematuria in children by measurement of mean corpuscular volume of urinary red cells using a semi-automated cell counter.

Urine samples from 110 children and adolescents with micro- or macrohematuria were compared using phase-contrast microscopy and a semi-automated cell counter to differentiate glomerular from non-glomerular hematuria. Glomerular hematuria, defined by clinical criteria from biopsy and standard chemical evaluation, was observed in 73 patients (group 1): non-glomerular hematuria was found in 37 patients (group 2). The latter group underwent urological operation and had normal urine before operation. Mean corpuscular erythrocyte volume (MCVU) and percent of dysmorphic erythrocytes were determinated. To exclude the influence of mean erythrocyte volume of blood erythrocytes (MCVB), MCVB was determined and additionally the quotient of MCVU/MCVB was calculated (MCVUB). The percentage of dysmorphic erythrocytes differed significantly between the two groups ((75 +/- 13% in group 1 versus 38 +/- 27% in group 2 (mean +/- SD); p < 0.01), MCVU (34.0 +/- 11.1 fl in group 1 versus 55.5 +/- 16.3 fl in group 2; p < 0.01) and MCVUB (0.41 +/- 0.14 in group 1 versus 0.67 +/- 0.20 in group 2; p < 0.01). When glomerular hematuria was defined on the basis of more than 80% dysmorphic erythrocytes, the sensitivity of phase-contrast microscopy was 0.52, specificity versus 0.96 and efficiency 0.64. When glomerular hematuria was defined as < 50 fl MCVU, sensitivity was 0.92, specificity 0.57 and efficiency 0.80 and as < 0.06 MCVUB, sensitivity was 0.89, specificity 0.62 and efficiency 0.80. The correlation coefficient between MCVU and dysmorphic erythrocytes was -0.71 (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Validity and reliability of 24h blood pressure monitoring in children and adolescents using a portable, oscillometric device.

Noninvasive 24h BP monitoring using portable devices is a new method for the diagnosis of arterial hypertension and for the control of antihypertensive therapy in adults. Recently, it is also used in juvenile hypertension. We now report on the validity and reliability of an oscillometric BP recorder (SpaceLabs 90207) widely used in children and adolescents. Single BP recordings with this monitor were compared with manual auscultation of Korotkoff sounds and with measurements by an other oscillometric device (Dinamap). SBP measured by the SpaceLabs monitor was 5 mmHg (2-10 mmHg, median and quartiles) higher than manual readings whereas there was no difference in DBP between these methods. With the Dinamap monitor, SBP was identical to manual readings but DBP was underestimated by 8.5 mmHg (1-13 mmHg). The 24h BP monitoring was performed in 101 children < 13 years of age and in 58 adolescents > 12 years of age. Seventy-eight per cent (64-89%) of all readings were complete in the younger probands and 91% (84-95%) in the older ones (P < 0.01). Measurements failed more often during daytime compared with nighttime in both groups. In conclusion, long-term BP monitoring using an oscillometric device is useful and reliable in adolescents and even in smaller children.

Adolescent↗