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Biomedical subjects

F Fyhrquist

Publications and source records attributed to F Fyhrquist.

At least 19 recordsLinked to original sources
PubMed1992

Endothelin-1 stimulates its own synthesis in human endothelial cells.

We studied whether endothelin-1 (ET-1) would affect its own synthesis. Human umbilical cord vein endothelial cells in methionine-poor culture medium containing [35S] methionine were treated with synthetic ET-1 or ET-3. Immunoprecipitation of 35 S-labeled ET-1 was performed with rabbit ET-1 antiserum. ET-1 caused an 40 +/- 4% (mean +/- SEM) increase of immunoprecipitable 35 S-labeled ET-1 as confirmed by its elution point in reversed phase high power liquid chromatography (HPLC). ET-3 caused a 23 +/- 2% increase in ET-1 concentration. Amplification of cDNA by PCR showed both ET-1 and ETB receptor mRNAs in human cord vein endothelial cells. We conclude that ET-1 increases its own synthesis in endothelial cells. This suggests a positive autocrine feed-back action of ET-1 on its own synthesis, an effect which is probably mediated by non-specific ETB receptors.

Cells, Cultured↗
PubMed1992

Pharmacokinetics and effects of atrial natriuretic factor during hypothermic cardiopulmonary bypass.

The pharmacokinetics of a bolus dose of synthetic atrial natriuretic factor (ANF) 50 micrograms and its effects on urine output, blood pressure and plasma renin activity have been studied in 5 patients undergoing hypothermic cardiopulmonary bypass for cardiac surgery. The half-lives of the fast and slow components were 2.4 min and 14.2 min, respectively. The volume of the central compartment was 16.7 l and the volume of distribution at steady-state was 38.9 l. The total plasma clearance was 3.8 l.min-1. ANF significantly increased urine output and decreased blood pressure, but it did not affect plasma renin activity.

Atrial Natriuretic Factor↗
PubMed1992

Human endometrial adenocarcinoma cells express endothelin-1.

The expression of endothelin-1 (ET-1) in five human endometrial adenocarcinoma cell lines was studied. Using specific radioimmunoassay, immunoreactive ET-1 was detected in conditioned medium from two of the cell lines (RL 952 and HEC 1A). In reverse-phase high-performance liquid chromatography (HPLC), synthetic ET-1 and immunoreactive ET-1 from conditioned media revealed the same elution profile. By amplification of cDNA using the polymerase chain reaction, normal human endometrium as well as cell lines RL 952 and HEC 1A were shown to express ET-1 mRNA. In addition, cell line HEC 1B and KLE, which did not produce measurable amounts of immunoreactive ET-1, contained ET-1 specific mRNA whereas cell line AN3CA had no detectable ET-1 mRNA and did not secrete immunoreactive ET-1.

Adenocarcinoma↗
PubMed1992

Cytokine and acute-phase reactant levels in serum of children with cancer admitted for fever and neutropenia.

Serum concentrations of tumor necrosis factor-alpha (TNF alpha), interleukin (IL)-1 beta, IL-6, and the acute-phase reactants C-reactive protein (CRP) and serum amyloid A (SAA) were measured on admission in 46 neutropenic children with cancer in 81 episodes of fever. The aim was to find out whether any of these variables would differentiate true bacteremia from fever due to other causes. In most episodes serum concentrations of TNF alpha and IL-1 beta were elevated. IL-6 was detectable in 68%, but the serum concentration was elevated in only 15%. SAA proved to be more sensitive than CRP for the early detection of bacteremia. However, not even SAA was sufficiently accurate at the individual level. We conclude that the cytokine and acute-phase protein levels found were related to the febrile response but did not correlate with documented bacterial etiology.

Acute-Phase Proteins↗
PubMed1992

Hormonal changes in patients with severe chronic congestive heart failure treated by ultrafiltration.

Plasma atrial natriuretic peptide (ANP), antidiuretic hormone (ADH), plasma renin activity (PRA), and circulatory haemodynamics were studied in five patients with chronic congestive heart failure undergoing ultrafiltration on two consecutive days. The patients were in the New York Heart Association class IV, and were considered candidates for heart transplantation. A mean of 3.3 +/- 0.5 litres of fluid was removed during each ultrafiltration. Plasma ANP concentration remained unchanged during ultrafiltration: 369 +/- 151 pg/ml at start and 316 +/- 116 pg/ml at the end, while plasma ADH concentration and PRA increased from 5.1 +/- 2.1 to 7.5 +/- 3.4 pg/ml (P less than 0.02), and 5.9 +/- 3.0 to 7.7 +/- 3.2 ng/ml (P less than 0.03) respectively (n = 10). After treatment, plasma ADH and PRA declined to baseline values within 1 h. Pulmonary artery, pulmonary capillary wedge, and right atrial pressures decreased significantly, while blood pressure and heart rate remained constant during ultrafiltration. A volume of 3.3 +/- 0.5 litres of fluid was removed, and caused an increase in colloid osmotic pressure from 22.0 +/- 3.0 to 33.7 +/- 3.9 mmHg (P less than 0.02). It was unexpected that plasma ANP concentration did not decline. Due to long-standing severe heart failure the atrial wall may have lost some of its elastic properties, resulting in less ability to adapt to reduced filling pressures. Accordingly, atrial wall stretch remained unchanged, explaining the constant ANP levels. Ultrafiltration treatment caused an increased responsiveness to diuretic therapy, and four patients survived long enough to receive heart transplants.

Adult↗
PubMed1992

Immunoreactive interleukin-6 in serum of patients with B-lymphoproliferative diseases.

Serum immunoreactive interleukin-6 (ir-IL-6) concentration was measured by radioimmunoassay in nine patients with chronic lymphocytic leukaemia (CLL), 16 patients with multiple myeloma (MM), 12 patients with monoclonal gammapathy of undetermined significance (MGUS), 22 patients with primary Sjögren's syndrome (SS), and in 32 control subjects. Measurable quantities of ir-IL-6 were detected in every sample studied. Patients with MGUS and SS had significantly higher serum ir-IL-6 (mean +/- SD) concentrations (337 +/- 92 ng l-1 and 299 +/- 100 ng l-1, respectively) than controls (92 +/- 77 ng l-1) and patients with CLL and MM (120 +/- 32 ng l-1 and 113 +/- 58 ng l-1, respectively). Longitudinal studies of ir-IL-6 concentration in a few patients with MM showed a decrease before remission and an increase prior to relapse, but no consistent pattern was detected. In conclusion, we found that serum ir-IL-6 levels are higher in patients with benign hypergammaglobulinaemic states than in patients with malignant neoplastic B-cell disorders.

Adult↗
PubMed1992

Secondary polycythaemia associated with nocturnal apnoea--a relationship not mediated by erythropoietin?

A polysomnographic study was undertaken in nine patients with unexplained polycythaemia and nine age- and sex-matched controls. Circulating plasma levels of immunoreactive erythropoietin (IrEPO) were analysed before and after sleep. Seven out of nine polycythaemia patients were found to have sleep-disordered breathing and fulfilled the criteria for the sleep apnoea syndrome. Erythrocyte volume fraction was by definition higher among polycythaemia patients, and showed a weak positive correlation with minimum oxygen saturation during sleep (P less than 0.05). However, plasma IrEPO did not differ between the two groups or between morning and evening samples within the respective groups. In a separate study, IrEPO was repeatedly analysed during sleep in a group of six patients with severe obstructive sleep apnoea and six matched controls. No correlation with severity of sleep-disordered breathing was found. None of these patients had polycythaemia, and there was no obvious diurnal variation in IrEPO levels. A nocturnal sleep study may be warranted in patients with unexplained polycythaemia. Obstructive sleep apnoea does not appear to be related to increased IrEPO levels, although polycythaemia has been reported as a relatively common finding in this disease.

Circadian Rhythm↗
PubMed1992

Raised plasma endothelin during acute migraine attack.

Endothelins are the most potent vasoconstrictor peptides known. Plasma endothelin (ET-1) concentrations were measured in eight migraine patients (mean age 44.5 years), two during an acute migraine attack with aura and six during an attack without aura. The mean ET-1 values were elevated in all migraine patients above the range of normal subjects, and were 10.6 (range 6.0-16.0) pg/ml in migraine patients and 3.8 (range 0.7-5.8) pg/ml in controls. We hypothesize that ET-1 may constrict cerebral vessels during the initial stage of the migraine attack.

Adult↗
PubMed1992

Fuel and fluid homeostasis during long-term exercise in healthy subjects and type I diabetic patients.

OBJECTIVE: This study was designed to examine metabolic and hormonal effects of long-term exercise in healthy subjects and insulin-dependent (type I) diabetic patients. RESEARCH DESIGN AND METHODS: Two studies were performed. First, 16 healthy males (32 +/- 3 yr) were studied during a semitriathlon competition (2 km swimming, 90 km biking, and 21 km running). Second, 9 type I diabetic males (41 +/- 2 yr) and 17 healthy matched control subjects were studied during a 75 km cross-country skiing race. Blood samples were taken before and immediately after exercise, and also during the ski race. RESULTS: During the semitriathlon race, serum insulin, C-peptide, glucagon cortisol, growth hormone ACTH, prolactin, and plasma renin activity increased two- to ninefold, whereas serum testosterone fell. Apart from a fall in magnesium, serum electrolyte concentrations remained unchanged. Before long-term skiing, patients reduced their insulin dose by 30-40%. They were hyperglycemic during the initial part of the race, but near normoglycemic thereafter. There were large interindividual variations in the increments of counterregulatory hormones, whereas serum testosterone and luteinizing hormone fell quite uniformly. Plasma renin activity and aldosterone concentrations rose similarly in diabetic and healthy subjects, whereas the rise in antidiuretic hormone was slightly greater in diabetic patients. During the initial part of the race, serum atrial natriuretic peptide fell in both groups. CONCLUSIONS: Severalfold increments in hormone concentrations contribute to the maintenance of fuel and fluid homeostasis during long-term exercise. With an appropriate adjustment of insulin dose and diet, also type I diabetic patients can participate in competitive long-term exercise.

Adult↗
PubMed1992

Raised plasma concentrations of endothelin-1 and -3 in marmosets with acute aortic stenosis: no relation to the renin-angiotensin system.

Plasma levels of endothelin (ET), plasma renin activity (PRA) and angiotensin II (Ang II) were measured in anaesthetized marmosets exposed to acute aortic stenosis proximal to the renal arteries. In vehicle experiments, ET rose from 5 +/- 2 to 38 +/- 4 pg ml-1, PRA from 5 +/- 2 to 99 +/- 21 ng ml-1 h-1 and Ang II from 21 +/- 4 to 213 +/- 76 pg ml-1. Administration of renin inhibitor and angiotensin converting enzyme inhibitor reduced PRA and Ang II to control levels, while the plasma levels of ET increased further (51 +/- 10 and 71 +/- 16 pg ml-1, respectively). During aortic stenosis the two isoforms ET-1 and ET-3 appeared in the circulation, while in conscious control animals only ET-1 was found. It is concluded that the increased plasma levels of ET in our primate model could not be ascribed to the increased circulating levels of PRA and Ang II.

Acute Disease↗
PubMed1992

Plasma atrial natriuretic factor during ethanol ingestion in volume-loaded subjects.

The present study was designed to test whether ethanol ingestion affects plasma atrial natriuretic factor (ANF) concentration in healthy volunteers. On the basis of previous studies showing that ethanol induces a diuretic response and a decrease in atrial size (atrial distension), it was hypothesized that ethanol intake might be associated with a decrease in plasma ANF level. To somewhat increase plasma ANF level, the subjects were slightly loaded with water before the trial. As compared with juice, ethanol, 1 g/kg within 1 hr, increased urine output [405 +/- 37 (mean +/- SEM) ml/hr vs. 197 +/- 20 ml/hr, P less than 0.001]. Left atrial size decreased similarly (P less than 0.001) with both drinks. Plasma ANF concentration did not change with either ethanol or juice during the 3-hr study period. No changes were observed in plasma arginine vasopressin concentration and plasma renin activity. Our results are in conflict with previous reports in fasted subjects showing significant changes in plasma concentrations of the same hormones. Thus, the basal fluid balance seems to be crucial to the hormonal response to ethanol. The plasma concentrations of the hormones measured in this study do not directly explain the diuretic response to ethanol observed in slightly volume-loaded subjects.

Adult↗
PubMed1991

Endothelin-1 is expressed and released by a human endothelial hybrid cell line (EA.hy 926).

A permanent vascular endothelial cell line, EA.hy 926, was shown to express endothelin-1 (ET-1) mRNA and to secrete big ET-1 and ET-1 into culture medium. The concentration of both big ET-1 and ET-1 was significantly increased in EA.hy 926 culture medium by phosphoramidon, a metalloproteinase inhibitor, suggesting that phosphoramidon sensitive protease(s) may be responsible for the degradation of ET-1 and big ET-1. EA.hy 926 cells responded to various regulators of ET-1 similarly as primary human vascular endothelial cells. The production of ET-1 was increased by thrombin and decreased by vasodilators such as atrial natriuretic peptide, brain natriuretic peptide and nitroprusside, and by 8-bromo cyclic GMP and papaverine. This continuous human endothelial hybrid cell line could facilitate studies of regulation of ET-1 production in human endothelial cells, which in primary cultures have limited replication potential.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1991

Autosomal dominant erythrocytosis caused by increased sensitivity to erythropoietin.

We describe here a family with autosomal dominant erythrocytosis. In in vitro cultures, performed using the methyl cellulose assay, the number of erythroid colonies was normal or marginally increased when a standard concentration of erythropoietin (Epo) was used, but at lower Epo concentrations, the investigated persons formed more colonies than the controls. The difference was generally greater the lower the Epo concentration became. Some erythroid colony growth was seen even in the absence of any added Epo (apart from the minute concentration found in fetal calf serum), a phenomenon not seen in the controls. This finding indicates that the erythrocytosis in this family is caused by hypersensitivity of erythroid progenitors to Epo. The serum Epo concentration was low or low normal in all of the investigated family members, which is in good accordance with hypersensitivity to Epo. The erythrocytosis has not had any obvious effect on the health or life-span of the affected individuals. Many of them have reached an advanced age, and one of the affected family members has won several Olympic gold medals and world championships in endurance sports.

Erythropoiesis↗
PubMed1991

Prolonged neutral endopeptidase inhibition in heart failure.

We studied the hormonal, renal and hemodynamic effects of prolonged treatment with SCH 39370, a new neutral endopeptidase (NEP) inhibitor, in experimental congestive heart failure (CHF). Coronary-ligated CHF rats and sham-operated controls received vehicle or SCH 39370 30 mg/kg s.c. twice daily for six days. In rats with heart failure, SCH 39370 elevated the high plasma atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (cGMP) levels 2-fold both initially and at the end of the experiment. Initially, water balance was more negative in SCH 39370-treated CHF rats than in those treated with vehicle. In all SCH 39370-treated rats, ANP, cGMP and electrolyte excretion and diuresis were pronounced for 6 h after injection but attenuated thereafter. Blood pressure and pulse remained unchanged. On reverse phase high performance liquid chromatography (HPLC), ANP-(99-126) appeared to be the only circulating form of ANP in rats with heart failure. Three forms have been discovered in patients with heart failure. HPLC revealed only intact ANP in plasma of rats with heart failure during SCH 39370 treatment. NEP inhibitors may provide a new tool for treating chronic heart failure.

Animals↗
PubMed1991

Neuroendocrine activity in untreated heart failure.

Neuroendocrine activity was studied in 60 consecutive untreated patients with dyspnoea and a clinical suspicion of heart failure. On the basis of the so-called Boston clinical criteria the diagnosis of heart failure was regarded as unlikely in 26 patients, possible in 15 patients, and definite in 19 patients. These groups were studied before any drug treatment was started and were compared with a control group of 69 healthy individuals. Plasma atrial natriuretic peptide concentration was clearly raised in patients with definite heart failure and slightly raised in patients with possible heart failure. Plasma adrenaline concentration was somewhat raised in patients with definite or possible heart failure, whereas plasma noradrenaline concentration was raised only in patients with definite heart failure. Plasma renin activity was not increased in any of the patient groups and plasma aldosterone concentration was slightly increased only in patients with definite heart failure. In the total patient series there were significant correlations between plasma atrial natriuretic peptide concentration and markers of the severity of left ventricular dysfunction. There was some evidence of neuroendocrine activation in untreated heart failure: plasma concentrations of atrial natriuretic peptide and catecholamines were increased but the renin-angiotensin-aldosterone system showed little or no activation.

Aged↗