Biomedical subjects

L Kerp

Publications and source records attributed to L Kerp.

At least 37 records · Page 2Linked to original sources

PubMed1989

Modulation of catecholamine effects during hypoglycaemia in man by urapidil and propranolol.

The hypothesis that in hypoglycaemia adrenoceptor-blocking drugs may enhance those metabolic effects of the catecholamines that remain unblocked has been investigated in 12 volunteers. alpha-Adrenoceptor blockade with urapidil increased the heart rate and the plasma noradrenaline level, and increased the beta-adrenoceptor mediated cellular uptake of potassium and phosphate, and the production of lactate. Posthypoglycaemic glucose intolerance and the counterregulatory responses of hGH and cortisol remained unchanged. Plasma adrenaline, the alpha-adrenoceptor mediated responses of cortisol and hGH, and the diastolic blood pressure were increased by propranolol. Adrenoceptor blocking drugs produce an indirect stimulatory effect by eliciting a reflex increase in sympathetic tone, which is manifested as stimulation of receptors of the type that has not been blocked.

Adrenergic alpha-Antagonists↗

PubMed1989

The immune response to GHRH, relationship to conformation.

Antibodies to GHRH1-44, GHRH1-29, and proinsulin were induced in guinea pigs. GHRH1-44 forms 7 S and 10 S complexes with antibodies. It is a divalent antigen. The sequence 30-44 bound 85% of the antibodies to GHRH1-44 with high affinity (3.8 +/- 0.9 x 10(9) l/mol). The fragment 1-29 bound with low affinity (0.6 +/- 0.3 x 10(9) l/mol) 15% of the antibodies (2p less than 0.001). Antibodies to GHRH1-29 had low affinity towards the native hormone (0.4 +/- 0.2 x 10(9) l/mol) and the region 1-29 (0.3 +/- 0.2 x 10(9) l/mol). Antibodies to proinsulin bound linear C-peptide with lower affinity (0.3 +/- 0.2 x 10(9) l/mol) than the C-peptide loop in proinsulin (3.4 +/- 0.9 x 10(9) l/mol). It is concluded that the conformation of the epitopes on the sequence 1-29, recognized during the immune response, i.e. on the cell membrane, is different from the conformation of GHRH1-29 or GHRH1-44 in aqueous solution.

Animals↗

PubMed1989

Natural occurrence of IgE antibodies to peptide hormones in man.

IgE antibodies to peptide hormones or their fragments were investigated using specific radioallergosorbent tests. Ninety-six sera were obtained from otherwise healthy individuals with a positive RAST to at least one common allergen and without previous contact to exogenous hormones. Total serum IgE was normal (less than 300 ng ml-1) in 41 and elevated in 55 sera. Only one serum with normal total IgE had reagins to proinsulin. In sera with elevated total IgE positive tests (greater than 8 x background) were observed frequently: hGH 9.1%, GHRH1-44 5.5%, GHRH1-29 12.7%, erythropoietin 10.9%, human calcitonin 14.6%, salmon calcitonin 1.8%, ACTH 5.5%, insulin 14.6%, proinsulin 7.3%, insulin A chain 1.8%, insulin B chain 18.2, C-peptide 9.1%, and IGF 9.1%. The data show natural occurrence of reagins to peptide hormones in atopic persons. A risk at exposure to these peptides may exist in about 1% of the general population.

Autoantibodies↗

PubMed1989

IgE antibodies to human growth hormone prior to and during treatment.

Clinical manifestations of allergy to biosynthetic hGH were not reported in 245 patients treated for one year. A sensitive radioallergosorbent test showed, however, the presence of anti-hGH IgE antibodies in the sera of 13%. All patients with anti-hGH IgE had also elevated concentrations of total serum IgE, similar to atopic persons (2459 +/- 147 micrograms/l, normal 70 +/- 8, 2p less than 0.0001); 83% of all patients who had specific IgE antibodies to hGH had specific antibodies prior to treatment. Administration of hGH did not consistently change concentrations (up to 8 micrograms/l) or affinities (less than 10(7) to 1.3 X 10(9) l/mol) of the specific reagins. Anti-hGH IgE antibodies were related to atopy. Treatment with biosynthetic hGH did not significantly stimulate specific IgE.

Adolescent↗

PubMed1989

[Glucose tolerance and electrolyte metabolism in nifedipine and nifedipine dihydroergotoxin treated healthy subjects].

The effects of three oral doses of nifedipine 20 mg or nifedipine 20 mg/dihydroergotoxin 2 mg (Pontuc, HN 85) during three subsequent days on an oral glucose load (100 g) were compared to placebo. Neither drug altered the glucose load or inhibited the secretion of insulin or C-peptide. The fall of serum potassium was also identical to controls. Basal plasma norepinephrine concentrations were lower following nifedipine/dihydroergotoxine than after nifedipine alone (2 p less than 0.05). A decrease of the serum sodium concentration by 2 mmol/l was observed with nifedipine but not with the combined drugs.

Adult↗

PubMed1988

Beta 2-sympathomimetic activation as a cause of posthypoglycemic glucose intolerance.

Posthypoglycemic glucose intolerance is related to counter-regulatory hormones. We have tested the role of the beta 2-sympathomimetic activity of the catecholamines in healthy volunteers. beta 2-stimulation with fenoterol for 25 minutes caused glucose intolerance and insulin resistance for 4 hours. This suggests that the beta 2-sympathomimetic activity induces glucose intolerance after an episode of hypoglycemia.

Blood Glucose↗

PubMed1988

Metabolic effects of intravenous proinsulin.

Proinsulin induced hypoglycemia was characterized in eight healthy male volunteers. Proinsulin cleared slower from the circulation than insulin. The metabolic effects on plasma glucose, free fatty acids, glycerol, 3-hydroxybutyrate, potassium, and phosphate occurred slower. The anti-lipolytic effect of proinsulin was longer than that of insulin (2P less than 0.001). The hormonal responses of epinephrine, norepinephrine, prolactin, hGH, and cortisol were attenuated following proinsulin. The amount of epinephrine secreted during counterregulation and the amount of lactate produced in response to beta-stimulation were both correlated to the fall of plasma glucose (2P less than 0.005). Stress symptoms were milder after proinsulin (2P less than 0.01). The data obtained are consistent with the hypothesis that the slower kinetics of proinsulin cause slower metabolic effects. The assumption of non-insulin-like effects of a differing pattern of insulin-like effects is not necessitated by the results of this study.

3-Hydroxybutyric Acid↗

PubMed1987

Specificity of monoclonal anti-human insulin antibodies.

To define the specificity and epitope of five monoclonal antibodies (MoAbs) to human insulin, binding studies with artificially modified insulins and a number of native insulins were done. Epitopes on the A-chain (A4, A8-A10) and on the end of the B-chain (B30) could be identified. For two MoAbs, substructures of the amino acid B30 were found, which were essential for binding (hydroxyl and methyl groups of B30). In contrast to most antisera, MoAbs to human insulin show high specificity. However, as the study shows, the specificity is not absolute. With suitable artificial epitope modifications, cross-reaction can be seen. Two of the MoAbs used here show sufficient specificity to discriminate between insulin and proinsulin.

Animals↗

PubMed1986

Pharmacokinetics of a long-acting bromocriptine preparation (Parlodel LA) and its effect on release of prolactin and growth hormone.

The pharmacokinetics and endocrine actions of a long-acting form of bromocriptine (Parlodel) were examined in a controlled study in 10 healthy volunteers receiving a single i.m. injection of 50 mg. Six further subjects took bromocriptine 1.25 mg t.i.d. for 3 days p.o. In the subjects given the slow release preparation, the plasma bromocriptine concentrations increased sharply to a maximum of 1.65 mg/l 2 h after injection. This fast release process was followed by slow clearance with a half-life of 16 days. The substance was still detectable in plasma 35 days postinjection. Plasma prolactin (PRL) fell rapidly from a mean of 5.6 ng/ml to reach significantly lower levels at 60 and 120 min. Inhibition was maintained for up to 35 days, when plasma PRL was still significantly below the values recorded at baseline and in the control group. Plasma GH peaked at 3.6 ng/ml at 120 min and subsequently declined slowly to stabilize between 1.4 and 2.2 ng/ml for about 12 h, falling to below the 1 ng/ml limit for the remainder of the study period. In contrast, individuals receiving oral bromocriptine exhibited a significant elevation following the first dose and an equivalent increment after the morning dose on Day 3. Thus, the results show a prolonged inhibitory effect on PRL of this long-acting bromocriptine preparation in parallel with its slow plasma clearance. The stimulant effect on GH secretion is short lived, presumably due to desensitisation of specific receptors.

Adult↗

PubMed1986

Hypoglycemia following insulin and proinsulin. A comparison.

The counterregulatory hormonal response to proinsulin-induced hypoglycemia was investigated in eight volunteers. Proinsulin cleared slower from the circulation than insulin. Hypoglycemia occurred slower (2P less than 0.005) and was prolonged, while the overall hypoglycemic activities were comparable. The antilipolytic effect of proinsulin was also prolonged (2P less than 0.001). The response of epinephrine to hypoglycemia was less pronounced after proinsulin (2P less than 0.05). The amount of epinephrine was correlated to the rate of fall in plasma glucose (P less than 0.005). The production of lactate induced by beta-stimulation was also correlated to the fall of glucose (P less than 0.005). The responses of prolactin (2P less than 0.02), norepinephrine (2P less than 0.02), cortisol, and growth hormone were attenuated following proinsulin. The decreases of serum potassium and serum phosphate (2P less than 0.05) were less pronounced. Symptoms like sweating (2P less than 0.01) and dizziness (2P less than 0.01) were milder after proinsulin. It is concluded that the rate of fall in glucose concentration determines the differing counterregulatory responses. We don't relate the differing counterregulatory responses to special insulin-like properties of proinsulin, but to the slower kinetics which is emphasized by the intravenous bolus injection.

3-Hydroxybutyric Acid↗

PubMed1986

Variations in the size of growth hormone-antibody complexes.

Guinea pigs were immunized with extracted human growth hormone. Human sera were obtained after treatment with biosynthetic methionyl hGH. The size of hGH-anti hGH antibody complexes was determined from the sedimentation velocity at 100,000 g. At an excess of hGH over antibodies 8 S complexes were uniformly observed in human and guinea pig sera. S values between 11.8 and 15.6 were observed at antibody excess in individual guinea pig sera. Antibodies from humans treated with methionyl hGH formed smaller complexes (7.5 S). One patient with GH-deficiency developed resistance to treatment. Complexes of 12.3 S were formed by his antibodies. HGH sustains the formation of antibody complexes containing more than three IgG molecules (15.6 S). It is discussed that human antibodies of higher diversity may form complexes larger than trimers which initiate the complement cascade.

Animals↗

PubMed1986

Maturation of immune response to insulin. Recruitment of new epitopes by antibodies.

Guinea pigs were immunized with regular insulin in Freund's adjuvant weekly (N = 6) or with NPH insulin daily (N = 10). The concentrations, the affinities, and the sizes of the insulin-immunoglobin G (IgG) antibody complexes were determined by ultracentrifugation. During the immune response to insulin, 7-S complexes were observed after 3 wk, and 10-S complexes were observed after 4 wk (2P less than .05 in each group). "7-S" antibodies were transferred into immunized guinea pigs before the formation of measurable antibody concentrations. The development of 10-S structures was enhanced in outbred Pirbright white guinea pigs (2P less than .05, N = 6) and in inbred strain II l.b.m. guinea pigs (2P less than .05, N = 7). Insulin may act as a monovalent antigen (7 S) after 3 wk and become bivalent after 4 wk (10 S). The change in valency is enhanced by antibody transfer. It reflects the formation of antibodies recognizing new epitopes on insulin.

Animals↗

PubMed1985

Insulin secretion in vitro and insulin binding to isolated hepatocytes in congenic mice with different H-2 complexes.

Congenic male mice with differences in the H-2 complex have been used to investigate insulin secretion in vitro, insulin binding to isolated hepatocytes, plasma glucose, and serum insulin. Plasma glucose and serum insulin did not show consistent differences in the B10.BR, B10.D2, B10.A, B10.G, B10.M, B10.S, C57/10SCSN, and C3H.OH strains. Isolated islets of Langerhans responded to stimulation with 400 mg/dl glucose with a 3-5-fold increase in insulin secretion rates (2P less than 0.01): B10.BR greater than B10.M greater than C57BL/10SCSN greater than B10.G greater than C3H.OH, B10.D2, B10.A, B10.S. The biphasic pattern of insulin secretion was less distinct in B10.M, B10.G, and C3H.OH mice. The high-affinity constants of insulin binding to isolated hepatocytes at 37 degrees C varied between 4.5 X 10(7) L X mol-1 and 4.5 X 10(8) L X mol-1 (2P less than 0.01): B10.A greater than B10.BR greater than C57BL/10SCSN, B10.S, B10.D2 greater than B10.M, B10.G. The glucose-stimulated insulin secretion from isolated islets of Langerhans and the binding of insulin to isolated hepatocytes correlate to the H-2 complex independently.

Animals↗

PubMed1985

Insulin and anti-insulin antibody interaction. Evidence for the formation of 7 S and 10 S structures.

The clearing of monoclonal and polyclonal and anti-insulin antibodies from homogeneous solutions at 100,000 X g was used to estimate the size of soluble insulin-antibody complexes at physiologic concentrations. Monoclonal antibodies cleared as a uniform population of 6.6 S independent of the insulin concentration. Polyclonal antibodies cleared as 6.6 S monomers at saturation and as 10 S particles when the amount of insulin bound decreased, suggesting that a soluble complex with two antibodies was formed. An increase of the affinity and a decrease of antibody valency can be related to the complex formation. The binding affinity of polyclonal sera depends on the composition of the affinities of the IgG monomers and on their ability to form 10 S complexes. The formation of insulin-antibody dimers precludes cross-linking and precipitation. Both types of insulin-antibody complexes have been found in the sera from patients treated with bovine insulin.

Animals↗

PubMed1985

Recognition of human insulin and proinsulin by monoclonal antibodies.

High-affinity monoclonal antibodies (MAB) were obtained from lymph node cell fusions. Affinities ranging from 0.8 X 10(9) L/M to 5.2 X 10(9) L/M were calculated from binding studies with monoiodinated human, bovine, and porcine insulins and human proinsulin. Two monoclonal antibodies were specific for human insulin, recognizing an epitope involving the amino acid B-30 (Thr). Another two monoclonal antibodies were bound to the C-terminal end of the B-chain near B-30. The B-chain-specific monoclonal antibodies did not bind human proinsulin. One monoclonal antibody recognized the A-chain loop in the positions A-8 to A-10. This antibody bound also to human proinsulin. It was concluded that the A-chain loop is exposed on the surface of proinsulin, while the C-terminal B-chain is not available for binding. The study shows that monoclonal antibodies can be used to characterize structures of insulin and proinsulin. In contrast to x-ray studies, the molecules can be used at low concentrations in soluble form. It is suggested to use monoclonal antibodies for the screening of atypical insulins in the serum of diabetic patients and for the further refinement of insulin and proinsulin measurements.

Animals↗

PubMed1984

Evidence for coronary spasm during flushing in the carcinoid syndrome.

In this report we present the history of a patient with symptomatic carcinoid syndrome. During flushing he suffered from variant angina. The observation of coronary spasm due to excess 5-hydroxytryptamine (5-HT) is discussed with regard to the discharge of 5-HT from clotting platelets in the coronary arteries.

Aged↗

PubMed1984

Insulin receptor binding in pork brain: different affinities of porcine and human insulin.

The insulin receptor binding of human and pork insulin was measured in four different pork brain tissues. In medial hypothalamus, infundibulum of pituitary gland, neurohypophysis, and adenohypophysis insulin receptors were found. Binding of mono-125I-(TyrA14)-insulin proceeded rapidly at 37 degrees C, pH 7.4, and reached a steady state for human and pork insulin at 15 minutes. Biosynthetic human insulin and semisynthetic human insulin dissociated more rapidly than pork insulin. In the four tested brain tissues the specific insulin binding per mg protein differed significantly (2p less than 0.01). The receptor affinity constant of human insulin was significantly (2p less than 0.01) lower in comparison to pork insulin in the four brain tissues studied. This study demonstrates that there are insulin receptors in pork brain tissue, that the amounts of these receptors vary depending on the area and that the brain insulin receptors react differently to pork and human insulin.

Animals↗

PubMed1984

[Reversible orthostatic hypotension during vincristine therapy].

A 69-year old patient with high-grade malignant lymphoma experienced severe orthostatic hypotension during vincristine therapy. The symptoms disappeared when vincristine treatment was discontinued. The mechanism of the orthostatic hypotension is discussed.

Aged↗