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Biomedical subjects

E Hartter

Publications and source records attributed to E Hartter.

At least 19 recordsLinked to original sources
PubMed1992

Construction and use of two alpha-human atrial natriuretic peptide-fragment affinity chromatography columns in the isolation of C- and N-terminal epitope-specific antibodies for use in a prototype alpha-hANP biosensor.

Two alpha-human atrial natriuretic peptide (alpha-hANP) based affinity chromatography columns were produced by covalently immobilizing the C- and N-terminal epitopes of alpha-hANP. The stationary phase was made from a controlled-pore-glass bead solid support, which was silanized and treated with sulphosuccinimidyl 4-(maleimidomethyl)cyclohexyl carboxylate before the individual fragments were immobilized by substitution at their thiol groups. These columns were used to isolate alpha-hANP-specific antibodies from a goat anti-alpha-hANP serum, which were then further sorted according to their epitope specifity. These C- and N-terminal epitope-specific antibodies were in turn used as components in the construction of an alpha-hANP biosensor based on an enzyme-linked immunosorbent assay (ELISA) sandwich principle. Initial in vitro testing of the sensor using a physiological alpha-hANP solution showed a reproducible response to the peptide. There is to date no other equally fast, sensitive and precise method available to detect this peptide. This alpha-hANP sensor may prove to be an invaluable aid in human medicine as a monitor of patient status during transplant surgery, for example, an area inaccessible to radioimmunoassay and normal ELISA techniques.

Amino Acid Sequence↗
PubMed1992

[Effects of treatment of arrhythmias requiring therapy in dilated cardiomyopathy with amiodarone on alpha human atrial natriuretic peptide].

In a longitudinal study comprising a total of 18 patients, the paradoxical time course of hANP plasma levels, i.e. the reproducibility of the low levels previously reported in cases of extreme cardiac insufficiency after administration of amiodarone, was investigated over a period of 9 months. At the same time, the effect of the degree of cardiac insufficiency and arrhythmia on the secretion of hANP was observed. The patients had been admitted to hospital because of the diagnoses "cardiac insufficiency secondary to cardiomyopathy" or "Grade IVb arrhythmia according to Lown's classification". During in-patient treatment, antiarrhythmic therapy was commenced in all patients. Clinical examinations and determinations of humoral parameters during therapy showed a substantial number of patients, who exhibited no increase in hANP levels despite massive cardiac decompensation. As far as drug therapy of patients with severe arrhythmias secondary to congestive (dilated) cardiomyopathy is concerned, amiodarone has proved to be the drug of choice in combination with digitalis, ACE inhibitors and diuretics. There is a close correlation between the degree of cardiac insufficiency and plasma hANP levels.

Aged↗
PubMed1992

Increased levels of plasma amylin in advanced renal failure.

Amylin, a 37 amino acid polypeptide, has been suggested to play a prominent role in the pathogenesis of insulin resistance in type II diabetes mellitus. Various studies have demonstrated most recently that amylin is cosecreted with insulin. No data are available on the elimination of amylin from the circulation. We therefore tested plasma levels of amylin, insulin and C-peptide in 49 non-obese, non-diabetic patients (27 male/22 female) with various degree of renal impairment (Group A: CCr less than 20 ml/min, n = 20; Group B: CCr 20-89 ml/min, n = 18; and Group C: CCr greater than 80 ml/min, n = 9). We found a significant increase of plasma amylin when kidney function, expressed by creatinine clearance fell below 20 ml/min (17.9 +/- 1.7 vs. 12.2 +/- 0.8 vs. 8.8 +/- 1.2 pg/ml; p = 0.0005). Plasma amylin correlated closely with serum C-peptide (r = .764; p = 0.0001), and to a lesser extent with insulin (r = .595; p = 0.0001) underlining its postulated cosecretion with these peptides. The data indicate that amylin might be eliminated by renal mechanisms. Our data show that besides type II diabetes mellitus, advanced renal failure is another clinical situation with enhanced plasma amylin levels. Whether amylin plays any pathogenetic role in renal patients remains to be elucidated.

Amyloid↗
PubMed1991

Basal and stimulated plasma levels of pancreatic amylin indicate its co-secretion with insulin in humans.

Amylin is a 37-amino acid pancreatic polypeptide, probably involved in the pathophysiology of Type 2 (non-insulin-dependent) diabetes mellitus. We have determined amylin in human plasma by extraction-based radioimmunoassay (Sep-Pak C18). Of 23 healthy control subjects plasma amylin was determined as 11.9 +/- 3.5 ng/l. Of 27 patients with Type 2 diabetes receiving insulin the amylin levels were lower, and in 16 patients with Type 2 diabetes on oral medication they were higher than in the control subjects; 8.2 +/- 4.4 ng/l (p less than 0.01) vs 18.8 +/- 9.9 ng/l (p less than 0.05). In 14 Type 1 (insulin-dependent) diabetic patients we found extremely low mean amounts of amylin: 2.9 +/- 1.9 ng/l (p less than 0.002). Thus, basal amylin appears to be associated with the capacity to release insulin. An oral glucose load stimulated the release of amylin, this was more pronounced in patients with Type 2 diabetes than in healthy subjects. An excellent correlation of mean amylin with mean insulin concentrations was obtained (r = 0.949). In patients with Type 2 diabetes amylin was reduced congruent to decreases in C-peptide during a hyperinsulinaemic, euglycaemic glucose clamp experiment (r = 0.971 for linear correlation between C-peptide levels and amylin). We conclude, that amylin and insulin are co-secreted in humans, and that the amylin release is under feedback-control by insulin.

Adult↗
PubMed1991

Raised circulating plasma levels of atrial natriuretic peptide in adolescent and adult patients with cystic fibrosis and pulmonary artery hypertension.

Since pulmonary artery hypertension (PH) complicates advanced stages of cystic fibrosis (CF), we wondered whether plasma concentrations of h-ANP would be increased in adult patients with CF. Furthermore, if only the right ventricle is faced with an increased afterload in these patients, the increased h-ANP plasma levels should stem primarily from the right atrium. To test this hypothesis we studied 12 adult patients with CF in a clinically stable condition using right heart catheterization. Mean pressures were measured in the right atrium (Pra) and pulmonary artery (Ppa), pulmonary capillary wedge (PCWP) position, and blood were drawn from the pulmonary artery and from a peripheral vein to determine h-ANP. Plasma levels in the pulmonary artery were significantly higher than in a peripheral vein (54.3 +/- 6.0 pg/ml vs. 32.2 +/- 4.4 pg/ml; p less than 0.001). Four of the 12 patients had PH (Ppa, 25.8 +/- 2.9 mmHg) whereas 8 patients exhibited normal pulmonary artery pressures (Ppa, 15.9 +/- 0.7 mmHg). Patients with PH had higher Pra (4.2 +/- 0.4 mmHg) than patients with CF without PH (1.9 +/- 0.7 mmHg; p less than 0.05). Plasma h-ANP concentrations were significantly higher in patients with CF with PH (70 +/- 10.4 pg/ml in the pulmonary artery; 42.6 +/- 4 pg/ml in a peripheral vein) than in patients with normal pulmonary artery pressure (43 +/- 3.3 pg/ml in the pulmonary artery; p less than 0.01; 24.7 +/- 5.6 pg/ml in a peripheral vein; p less than 0.05). Although our results are derived from a small group of patients with CF, we conclude from our results that in patients with CF PH may cause increased h-ANP secretion. The right atrium seems to be a major source.

Adolescent↗
PubMed1991

Decrease of stimulated amylin release precedes impairment of insulin secretion in type II diabetes.

Amylin, a 37-amino acid polypeptide, has been identified as the major protein component of pancreatic amyloid deposits in patients with non-insulin-dependent (type II) diabetes mellitus. Amylin is stored and released together with insulin and has been proposed to play a major role in the pathogenesis of type II diabetes. To compare amylin release and its proportion to insulin secretion under different metabolic conditions, oral and intravenous glucose tolerance tests (OGTT and IVGTT, respectively) were performed in healthy, lean control subjects, obese patients with normal and impaired glucose tolerance (NGT and IGT, respectively), and obese type II diabetic patients. Compared with control subjects, basal and stimulated amylin secretion during OGTT was significantly higher in obese patients with NGT and IGT but not in type II diabetic patients. The integrated amylin response was significantly higher in obese patients with NGT than lean control subjects and type II diabetic patients matched for degree of obesity. The amylin-insulin ratio decreased slightly in obese subjects with NGT and IGT and significantly in type II diabetic patients. Amylin secretion was significantly stimulated during IVGTT in control subjects and obese patients with NGT and IGT but not in type II diabetic patients. These findings suggest that amylin is physiologically released by pancreatic beta-cells in a constant ratio to insulin in nondiabetic subjects. Glucose-stimulated amylin secretion is increased in obese subjects with NGT and IGT. In type II diabetes mellitus, amylin secretion relative to that of insulin is decreased, and amylin is not stimulated by IVGTT.

Adult↗
PubMed1991

[Role of amylin in the pathogenesis of type II diabetes mellitus].

Amylin, a peptide, which was isolated from the islet amyloid of type II diabetics, might play a potential role in the pathogenesis of type II diabetes mellitus. In in vitro and in vivo studies it has been shown that amylin has an effect on insulin secretion as well as on insulin sensitivity. From measurements of plasma amylin levels it is known that amylin is cosecreted with insulin and patients with hyperinsulinemia have also elevated amylin levels. In patients with impaired glucose tolerance and type II diabetes amylin levels are decreased compared to insulin. A secretory defect of amylin and its local accumulation in the islets of type II diabetics might be a cause for the insulin secretory defect in type II diabetes. Additionally, amylin can induce peripheral insulin resistance, which might also be a cause for type II diabetes mellitus. Amylin is a new pancreatic peptide, which might play an important role in the pathogenesis of diabetes mellitus.

Amyloid↗
PubMed1991

Radioimmunoassay of immunoreactive C-terminal big-endothelin(22-38).

Endothelin, a potent endogenous vaso-constrictor, is derived from its biosynthetic precursor by proteolytic degradation. The last step cleaves big-endothelin(1-38) to endothelin(1-21) and a C-terminal fragment. We have developed a radioimmunoassay for this peptide, based on an antiserum recognizing the C-terminal sequence big-endothelin(22-38) and cross-reacting with intact big-endothelin. To test for the presence of immunoreactive big-endothelin(22-38) in plasma, samples were extracted by passage through C18 silica cartridges, and desorption with methanol/water volume fraction 0.8. The yields of this purification and concentration procedure were about 70%. In 15 healthy persons we found concentrations of 1-11 pmol/l, which is about 10-fold higher than the reference levels reported for endothelin(1-21) or big-endothelin(1-38). Thus, endothelin-derived peptides containing the big-endothelin(22-38) sequence, but different from intact big-endothelin, do circulate in human blood. If a sufficiently tight correlation to levels of circulating endothelin(2-21) can be proven, this would facilitate studies on the physiological role of endogenous endothelin.

Endothelin-1↗
PubMed1990

Immobilization of alpha-human atrial natriuretic peptide on insoluble supports and affinity purification of specific antibodies from a polyclonal goat anti-alpha-human atrial natriuretic peptide serum.

alpha-Human atrial natriuretic peptide (alpha-hANP) was covalently coupled via single attachment onto two different insoluble matrices. Controlled-pore glass-alpha-hANP matrices were well suited for the purification of monospecific antibodies, whereas Enzacryl AA-alpha-hANP did not withstand the inevitable chemical and physical stresses during affinity purification.

Animals↗
PubMed1990

Determination of alpha-human atrial natriuretic peptide (alpha-hANP) in urine using combination HPLC with RIA strongly indicates non-immunoreactive metabolites.

Employing HPLC coupled with RIA, it was shown that alpha-human atrial natriuretic peptide is excreted in urine. Freshly collected urine had to be acidified to obtain reproducible results. When prepurified urine was subjected to HPLC (ion exchange and reversed phase) the subsequent quantification of alpha-hANP immunoreactive material in the eluate showed 10- to 30-fold greater amounts of alpha-hANP after treatment with HPLC; substances with the same elution parameters as synthetic alpha-hANP were detected, but they gave no response in the RIA.

Atrial Natriuretic Factor↗
PubMed1990

Interpretation of plasma concentrations of human atrial natriuretic peptide (hANP) in congestive heart failure.

The present study reports about novel findings concerning the interrelationship between release of human atrial natriuretic factor (hANP) and the clinical situation of patients suffering from congestive heart failure. Estimations of plasma hANP were done by specific and sensitive extraction-based RIA. The normal range was 5 to 80 ng/l, mean +/- SEM = 30 +/- 15 ng/l, n = 106. Influence of response to therapy on hANP-release was studied in altogether 14 patients. 12 of these patients had elevated plasma hANP at admittance, surprisingly peptide levels were normal in 2 patients throughout the study. 9 out of the 14 patients responded well to therapy (shift from NYHA IV/III to NYHA II within about 10 days), hANP-levels decreased to normal values: 235 +/- 104 ng/l vs. 65 +/- 13 ng/l; p less than 0.001. The 5 residual patients responded to therapy only partially (shift from HYHA IV to NYHA III within an observation interval of about 2 weeks). Plasma hANP values decreased from 225 +/- 94 ng/l to 137 +/- 22 ng/l (p less than 0.02), but were still supranormal. Atrial fibrillation, which persisted in 8 out of the 14 patients after therapy did not influence hANP levels: hANP levels paralleled clinical signs of improvement, irrespective of atrial fibrillation. Right heart catheterization revealed very high mean right atrial pressures in those 2 patients mentioned above, who had normal pretherapeutic hANP.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Fibrillation↗
PubMed1989

Correlation between heart disorders and concentrations of directly measured atrial natriuretic peptide in plasma.

We used new commercially available direct radioimmunoassay to measure human atrial natriuretic peptide (h-ANP) in plasma from 48 individuals who were being evaluated for left and right ventricular function. For 13 healthy individuals with normal ventricular function these concentrations ranged up to 54 ng/L. Measurements of h-ANP clearly differentiated between normal subjects, patients with coronary artery disease, and patients who had undergone orthotopic heart transplantation (ANOVA P less than 0.0001, significant differences between all groups)--all showing normal ventricular function at rest. There was a strong negative correlation (r = -0.64, P less than 0.001) between left ventricular ejection fraction and h-ANP concentrations in plasma of patients with proven coronary artery disease, patients with cardiomyopathy, and healthy individuals. Results by the present method and methods involving extraction of the sample correlated well. Evidently the direct assay of h-ANP in plasma yields information that could be used to help evaluate heart disorders and other pathophysiological conditions causing increased h-ANP concentrations in plasma.

Adult↗