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P Nowotny

Publications and source records attributed to P Nowotny.

At least 91 records · Page 5Linked to original sources
PubMed1993

Equivalent discrimination among states of thyroid function by immunochemiluminimetric and immunoradiometric determination of thyrotropin.

New immunochemiluminometric assays (ICMA) of thyrotropin (TSH) have been reported to facilitate the diagnosis of hyperthyroidism. To compare the accuracy of ICMA-TSH with that of a conventional immunoradiometric assay (IRMA-TSH), we examined 115 consecutive patients of a thyroid outpatient clinic. On the basis of complete thyroid-function testing, including thyroliberin tests, the untreated patients (n = 89) were subclinically hyperthyroid (n = 21), subclinically hypothyroid (n = 13), or euthyroid (n = 55). The receiver-operating characteristic (ROC) curve, used for comparing the TSH values obtained by these two methods, was shifted to the left for the IRMA-TSH. The area under the curve was greater for IRMA-TSH than for ICMA-TSH (0.984 vs 0.869, respectively), which suggests equal or better clinical performance of IRMA-TSH vs ICMA-TSH in discriminating between hyperthyroidism and euthyroidism. Both assays displayed similar clinical sensitivity/specificity for evaluating thyroid function in hypothyroid and treated patients. We conclude that the ICMA-TSH tested is not more accurate than an IRMA in distinguishing between hyperthyroidism and euthyroidism.

Adult↗
PubMed1992

Inter-protein distances within the large subunit from Escherichia coli ribosomes.

Selected pairs of protonated ribosomal proteins were reconstituted into deuterated 50S subunits from Escherichia coli ribosomes. The rRNA of the deuterated ribosomal matrix was derived from cells grown in 76% D2O, the deuterated protein moiety from cells grown in 84% D2O. This procedure warrants that the coherent neutron scattering of deuterated proteins and rRNA is nearly the same and equals that of a D2O solution of approximately 90%. The neutron scattering is recorded in a reconstitution buffer containing approximately 90% D2O. The result is a significant improvement of the coherent signal:noise ratio over traditional methods; due to this dilute solutions can be used, thus preventing unfavorable inter-particle effects. From the diffraction pattern the distance between the mass centers of gravity of the two protonated proteins can be deduced. In this way, 50 distances between proteins within the large subunit have been determined which provide a basis for future models of the large ribosomal subunit describing the spatial distribution of the ribosomal proteins. A model containing seven ribosomal proteins is presented.

Deuterium↗
PubMed1992

Effects of islet amyloid polypeptide on hepatic insulin resistance and glucose production in the isolated perfused rat liver.

The impact of (pancreatic) islet amyloid polypeptide on glucose metabolism and insulin sensitivity was examined in isolated rat livers perfused in a non-recirculating system. Continuous infusion of 10(-7) mol/l islet amyloid polypeptide affected neither basal nor glucagon (10(-9) mol/l)-stimulated glucose output by livers from fed rats, but it did increase the hepatic cyclic AMP release within 44 min (7.91 +/- 12.07 vs control: 0.07 +/- 0.03 pmol x 100 g body weight-1). The effect of the peptide on the ability of insulin to inhibit glucagon-induced hepatic glycogenolysis was measured in three experimental groups (n = 6). As expected glucagon (7 x 10(-11) mol/l) increased integral hepatic glucose release within 84 min (763.4 +/- 161.7 vs -25.7 +/- 73.2 mumol x 100 g body weight-1 in the control group, p less than 0.001), while insulin (100 mU/l) decreased the glucagon-stimulated glucose production (395.2 +/- 180.0 mumol x 100 g body weight-1, p less than 0.01). Simultaneous infusion of 10(-7) mol/l islet amyloid polypeptide however, was not able to reverse insulin-dependent inhibition of glucagon-stimulated hepatic glucose output (370.0 +/- 102.5 mumol x 100 g body weight-1, NS) or to enhance lactate-induced gluconeogenesis of livers from 24 h fasted rats (n = 8). The glucose production stimulated by 10(-9) mol/l glucagon was slightly greater in islet amyloid polypeptide-pre-treated livers than in a control group without addition of islet amyloid polypeptide (5 min: 3.60 +/- 3.36 vs 1.67 +/- 1.28 mumol.min-1 x 100 g body weight-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Amyloid↗
PubMed1992

Regional hemodynamic effects and clearance of endothelin-1 in humans: renal and peripheral tissues may contribute to the overall disposal of the peptide.

We investigated the regional balance of endothelin-1 across the renal and leg vascular bed as well as the hemodynamic effects of exogenously administered endothelin-1 in six healthy men. Net regional endothelin-1 balance was calculated from the respective arteriovenous differences in plasma concentrations and the corresponding plasma flow, the latter being determined by para-aminohippurate or indocyanine-green dye using appropriate catheter techniques. During constant intravenous (i.v.) infusion of endothelin-1 (0.4 pmol/kg/min), a slight increase in diastolic blood pressure (p less than 0.05) and a decrease in heart rate (p less than 0.01) were observed. In contrast, no significant changes in leg hemodynamics were noted. Renal plasma flow decreased by approximately 30%, and renal vascular resistance increased by 50% as compared with the control (placebo) period (p less than 0.01). Renin plasma concentrations did not change substantially during endothelin-1 infusion. During the control (placebo) period, arterial endothelin-1 plasma concentrations averaged 2.1 +/- 1.0 pM. An equilibrated peptide balance across the leg and a slight renal uptake of endothelin-1 was observed. After endothelin-1 infusion, arterial plasma concentrations of the peptide increased to 4.9 +/- 1.3 pM (p less than 0.01), and a net overall renal and limb uptake of endothelin-1 accounted for approximately 9 and 6% of the infused endothelin-1 amount, respectively. Results showed that at systemic endothelin-1 plasma concentrations, comparable to those which occur in a variety of pathologic conditions such as hypertension or cardiogenic shock, besides pulmonary clearance, renal and limb uptake of the peptide may also contribute to the short half-life (t1/2) of endothelin-1 in humans.

Adult↗
PubMed1992

Regional effects and clearance of endothelin-1 across pulmonary and splanchnic circulation.

To determine the impact of i.v. endothelin-1 on systemic, pulmonary and splanchnic circulation, as well as the peptide's regional clearance, hepatic venous and right heart catheterization was performed in healthy volunteers. During the peptide's continuous i.v. administration (0.4 pmol x kg-1 x min-1, 60 min) its plasma concentration rose from 2.1 +/- 0.5 to 9.5 +/- 5.3 pmol/l (pulmonary artery), from 2.1 +/- 0.9 to 5.0 +/- 1.6 pmol/l (femoral artery), and from 1.5 +/- 0.6 to 2.9 +/- 1.2 pmol/l (hepatic vein). This was accompanied by an increase in mean systolic arterial pressure from 127 +/- 14 to 131 +/- 12 mmHg (P less than 0.05). Concomitantly, cardiac output and heart rate decreased from 7.0 +/- 1.1 to 5.8 +/- 1.0 l/min and from 63 +/- 6 to 56 +/- 5 beats/min, respectively, while total vascular resistance increased from 964 +/- 273 to 1204 +/- 338 dyn x cm x s-5 (P less than 0.01). No major changes in pulmonary circulation were observed, while splanchnic vascular resistance increased from 4472 +/- 1056 to 5361 +/- 1420 dyn x cm x s-5 (P less than 0.01) and estimated hepatic blood flow decreased from 1403 +/- 218 to 1218 +/- 219 ml min-1 (P less than 0.01). During endothelin-1 infusion the pulmonary vascular bed accounted for approximately 53% of the peptide's overall disposal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Effect of endothelin-1 in man: pretreatment with nifedipine, with indomethacin and with cyclosporine A.

The rise in blood pressure following the intravenous administration of endothelin-1 remained unchanged in healthy male volunteers pretreated with either the calcium-channel antagonist nifedipine (10 mg orally), the cyclo-oxygenase inhibitor indomethacin (150 mg day-1 for three days) or the immunosuppressive agent cyclosporine (5 mg kg-1 body weight for five days). Following administration of nifedipine the rise in plasma concentrations of endothelin-1 during the infusion of the peptide was markedly higher (P less than 0.01) than during control experiments without nifedipine. It is concluded that, in healthy men, nifedipine, indomethacin and cyclosporine do not exert a major influence on the pressor action of endothelin-1. However, nifedipine apparently influences the elimination of endothelin-1 from the circulation in healthy men.

Adult↗
PubMed1992

Diminished release of atrial natriuretic factor in calves with a total artificial heart.

Venous hypertension after total artificial heart (TAH) replacement, a common problem in humans as well as experimental animals, is thought to be related to reduced release of atrial natriuretic factor (ANF) due to atrial damage. To verify this hypothesis, we stimulated the release of ANF in 6 calves before (-7 days) and after TAH replacement (+25, +50, +80, and +100 days) by the rapid (+ = 10 min) infusion of 2 L of Ringer's solution. In normal calves (-7 days) this procedure induced a rise in plasma concentration of ANF from 18.5 +/- 12 to 31.6 +/- 12 pmol/L (p < 0.05). After TAH the ANF release continuously decreased (analysis of variance, p < 0.02). Thus, ANF increased by 9.8 +/- 9.3, 6.8 +/- 17.5, 0.4 +/- 5.2, and 0.5 +/- 3.2 pmol/L at days 25, 50, 80, and 100, respectively. The central venous pressure increased by 3.4 +/- 1.5 mm Hg (before TAH) and by 6 +/- 2.9 mm Hg (after TAH) during this procedure. A decrease in plasma concentrations of aldosterone, most likely due to extracellular volume expansion and a decrease in total protein plasma concentrations and in hematocrit due to the dilution of blood, was seen in each experiment. Necropsy demonstrated massive atrial dilatation and myocardial dystrophy with atrial fibrosis. ANF granules were present to a small extent in every calf. We conclude that rapid intravenous infusion is an adequate stimulus to release ANF in normal calves. After TAH implantation the release of ANF by high venous pressure declines although ANF granules are still present in the damaged atrial stumps. Therefore, the loss of stimulated ANF could contribute to the observed increase in venous pressure in TAH calves although other pathophysiologic mechanisms cannot be excluded.

Aldosterone↗
PubMed1991

Modification of histidine residues on proteins from the 50S subunit of the Escherichia coli ribosome. Effects on subunit assembly and peptidyl transferase centre activity.

L2, L3, L4, L16 and L20 are proteins of the 50S ribosomal subunit of Escherichia coli which are essential for the assembly and activity of the peptidyl transferase centre. These proteins have been modified with the histidine-specific reagent, diethylpyrocarbonate, while L17 and L18 were treated as controls. Each modified protein tested was able to participate in the reconstitution of a 50S particle when replacing its normal counterpart, although the particles assembled with modified L2 were heterogeneous. However, although they could support assembly, modified L16 and L20 were not themselves reconstituted stably, and modified L2 and L3 were found in less than stoichiometric amounts. Particles assembled in the presence of modified L16 retained significant peptidyl transferase activity (60-70% at 10 mM diethylpyrocarbonate) whereas those reconstituted with modified L2, L3, L4 or L20 had low activity (10-30% at 10 mM diethylpyrocarbonate). The particles assembled with the modified control protein, L17, retained 80% of their peptidyl transferase activity under the same conditions. The histidine residues within the essential proteins therefore contribute to ribosome structure and function in three significant ways; in the correct assembly of the ribosomal subunit (L2), for the stable assembly of the proteins within the ribosomal particle (L20 and L16 in particular), and directly or indirectly for the subsequent activity of the peptidyl transferase centre (L2, L3, L4 and L20). The essential nature of the unmodified histidines for assembly events precludes the use of the chemical-modification strategy to test the proposal that a histidine on one of the proteins might participate in the catalytic activity of the centre.

Centrifugation, Density Gradient↗
PubMed1991

The effects of suramin on human adrenocortical cells in vitro: suramin inhibits cortisol secretion and adrenocortical cell growth.

Suramin, a polycyclic and polyanionic drug, has been successfully used in the therapy of inoperable adrenocortical cancer. The present study was undertaken to investigate the effects of suramin on normal human adrenocortical cells in primary monolayer cultures. The proliferation and the basal, as well as the adrenocorticotropin (ACTH)-stimulated, cortisol secretion of these cells were studied. The data show that suramin decreases basal, as well as ACTH-stimulated, cortisol secretion in a dose-dependent manner (P less than .05 from 300 mumol/L upward). At a suramin concentration of 3 mmol/L, cortisol secretion was inhibited by 70% +/- 4% in ACTH-stimulated cells and by 42% +/- 6% in unstimulated cells. The proliferation of adrenocortical cells in response to fetal calf serum was also inhibited by suramin at concentrations from 300 mumol/L upward, maximal suppression (71% +/- 6%, P less than .01) being observed at a concentration of 10 mmol/L. Both inhibition of cortisol secretion and inhibition of adrenocortical cell proliferation were not due to toxicity of the compound, as could be shown by restimulation of cortisol secretion in suramin-treated cells with ACTH. Our results indicate that suramin exerts an inhibitory influence on the cortisol secretion and on the proliferation of normal human adrenocortical cells. Suramin may not only be useful in the treatment of adrenocortical cancer, but may also have an ameliorative effect on other malignant conditions with augmented steroid hormone production, resistant to conventional forms of therapy.

Adrenal Cortex↗
PubMed1991

Inhibition by etomoxir of carnitine palmitoyltransferase I reduces hepatic glucose production and plasma lipids in non-insulin-dependent diabetes mellitus.

To determine the therapeutic effect of the carinitine palmitoyltransferase I (CPT-I) inhibitor, etomoxir, eight hospitalized obese non-insulin-dependent diabetes mellitus (NIDDM) patients were studied (body mass index [BMI], 28.7 +/- 1.3 kg/m2; age, 54 +/- 8 years [means +/- SE]) at baseline (placebo = t1), and after oral etomoxir (50 mg/d = t2, 100 mg = 3, 150 mg = t4, 200 mg = t5, placebo = t6). Fasting blood glucose (mmol/L), triglycerides (mmol/L), cholesterol (mmol/L), free fatty acids (mumol/L), beta-hydroxybutyrate (mumol/L), and alanine aminotransferase (GPT, U/L) were determined (t1 to t6), as were glucose utilization (M value; indirect calorimetry) and hepatic glucose production during a 10 mU/kg.min euglycemic clamp (t1 and t4). A dose-dependent decrease was induced by etomoxir in fasting blood glucose (t1 to t5: 9.5 +/- 0.7, 8.7 +/- 1.0, 8.3 +/- 1.1 [P v t1 less than .05], 7.8 +/- 0.9, [P v t1 less than .01], 7.9 +/- 1.1 [P v t1 less than .05]), which was reversible in t6 (9.9 +/- 1.1). Mean plasma lipids were reduced (t1 v t5) for triglycerides (-54%, P v t1 less than .01), cholesterol (-24%, P v t1 less than .05), and beta-hydroxybutyrate (-44%, P v t2 less than .01), while free fatty acids increased by 52% (P v t1 less than .05), as did GPT (t1: 17 +/- 3; t5: 32 +/- 7 U/L [P v t1 less than .01]).(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMed1991

Diagnostic relevance of suppressed basal concentrations of TSH compared with the negative TRH test in detection and exclusion of hyperthyroidism.

To evaluate the sensitivity of basal TSH concentrations as determined by an "ultrasensitive" IRMA-assay (RIA-gnost h-TSH-monoclonal, Behring) versus a "negative" TRH test (defined as an increment of TSH less than or equal to 0.2 mU/l 20 min after administration of 400 micrograms TRH iv) in the diagnosis of hyperthyroidism we examined 193 consecutive patients from our thyroid outpatient clinic: 34 patients displayed hyperthyroidism (total T4: 184.4 +/- 26.0 mumol/l, effective thyroxine index: 1.25 +/- 0.08), whereas 12 had isolated T3-hyperthyroidism (total T3: 3.47 +/- 0.48 nmol/l). Employing the producer's definition of subnormal ("suppressed") bTSH concentrations (less than or equal to 0.1 mU/l), only 19 (41.3%) hyperthyroid patients would have been detected; on the other hand, one euthyroid patient would have been recognized false positively as hyperthyroid. Using the TRH test as criterion led to the correct diagnosis in 42 (sensitivity: 91.3%) hyperthyroid patients, whereas two had low bTSH concentrations (less than or equal to 0.5 mU/l), but a normal TSH response to TRH (greater than 2.0 mU/l). Raising the threshold concentration to 0.2 and, subsequently, to 0.4 mU TSH/l increased the number of correct results to 38 (sensitivity: 82.6%) and 43 (93.5%), respectively. This was associated with a concomitant decrease in specificity in the diagnosis of hyperthyroidism from 93.7 (0.1 mU/l) to 27.9% (0.4 mU/l). In conclusion, despite ultrasensitive methods for estimation of low TSH concentrations, the TRH test remains an irreplaceable tool for the correct diagnosis of hyperthyroidism.

Adult↗
PubMed1991

Impaired conversion of cortisol to cortisone in chronic renal insufficiency--a cause of hypertension or an epiphenomenon?

To study the possible impairment of 11 beta-hydroxysteroid-dehydrogenase in patients with chronic renal insufficiency, urinary excretion rates of the four main glucocorticoid-metabolites, tetrahydrocortisol, tetrahydrocortisone, allotetrahydrocortisol and allotetrahydrocortisone were determined by capillary gas chromatography in 22 patients with chronic renal insufficiency with (N = 15) and without (N = 7) hypertension, but without hemodialysis treatment. Whereas the sum of all 41 steroid metabolites determined by capillary gas chromatography was reduced (p less than 0.001) in patients with chronic renal insufficiency as compared with 22 healthy individuals, the relative contribution of the four glucocorticoid metabolites to total steroid excretion was similar in patients with renal insufficiency (22 +/- 12%) and in healthy subjects (20 +/- 5%). However, the excreted amount of tetrahydrocortisol exceeded that of tetrahydrocortisone in all but 3 (normotensive) patients with chronic renal insufficiency, but only in one healthy subject resulting, in patients with chronic renal insufficiency, in a ratio of tetrahydrocortisone vs tetrahydrocortisone of 0.7 +/- 0.4 (hypertensive patients 0.5 +/- 0.2; normotensive patients 1.1 +/- 0.4; controls 1.9 +/- 0.9, p less than 0.001 vs patients with chronic renal insufficiency). This ratio of tetrahydrocortisone/tetrahydrocortisol showed a correlation with serum concentrations of creatinine (p less than 0.001). These results provide indirect proof of an impaired conversion of cortisol to cortisone in moderate renal insufficiency and may suggest a relationship with the hypertension frequently seen in this group of patients.

Adult↗
PubMed1991

Metabolic effects of fish-oil supplementation in patients with impaired glucose tolerance.

To determine the impact of fish-oil supplementation on glucose and lipid metabolism in patients with impaired glucose tolerance (IGT), 30 ml fish oil containing 3.8 g eicosapentaenoic acid (EPA; 20:5 omega 3) and 2.5 g docosahexaenoic acid (DHA; 22:5 omega 3) were given to eight obese subjects with IGT (mean +/- SD age 50.3 +/- 8.0 yr) in addition to their regular diet for 2 wk. Studies were performed in randomized order versus an isocaloric control period with a washout phase of 3 wk. Hyperinsulinemic clamp examinations (1 and 10 mU.kg-1.min-1) were performed. Glucose disposal rate (M value) rose from basal 14.3 +/- 5.1 to 17.9 +/- 4.4 mumol.kg-1.min-1 after fish oil (P less than 0.001) during the 1-mU clamp, whereas no change was seen during the 10-mU clamp (without fish oil, 42.2 +/- 8.9 mumol.kg-1.min-1; with fish oil, 45.1 +/- 9.8 mumol.kg-1.min-1;NS). Basal hepatic glucose output remained unaffected by fish oil, whereas fractional glucose clearance after intravenous glucose loading (2.4 mmol/kg body wt, t = 30 min) tended to increase (K value: without fish oil, 2.15 +/- 1.02%/min; with fish oil, 2.74 +/- 1.26%/min; NS). Neither the fasting concentrations of glucose and insulin nor induced glycemia and insulin response during intravenous glucose loading calculated as incremental area under the curve changed after fish-oil supplementation.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1991

Suramin and the human adrenocortex: results of experimental and clinical studies.

Suramin, a sulfonated drug, has been used successfully in the treatment of inoperable adrenocortical cancer. This study was undertaken to investigate the effects of suramin on the basal and the adrenocorticotropin-stimulated cortisol and pregnenolone secretion and on the proliferation of primary monolayer cultures of normal human adrenocortical cells. Suramin decreases basal and adrenocorticotropin-stimulated cortisol secretion in a dose-dependent manner (p less than 0.05 from 0.3 mmol/L upward). At a suramin concentration of 3 mmol/L cortisol, secretion was inhibited by 70% +/- 4% in adrenocorticotropin-stimulated cells and by 42% +/- 6% in unstimulated cells. The proliferation of adrenocortical cells in response to fetal calf serum was inhibited by suramin at concentrations from 0.3 mmol/L upward, maximal suppression (71% +/- 6%; p less than 0.05) being observed at a concentration of 10 mmol/L. Neither down-regulation of cortisol secretion nor inhibition of adrenocortical cell proliferation was caused by toxicity of the compound, as could be shown by adrenocorticotropin-restimulating cortisol secretion in suramin-treated cells. The results indicate that suramin exerts an inhibitory influence on the cortisol secretion and the proliferation of normal human adrenocortical cells and may be useful in treating adrenocortical cancer.

Adrenal Cortex↗