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Biomedical subjects

V Kruse

Publications and source records attributed to V Kruse.

At least 19 recordsLinked to original sources
PubMed1997

Fate of insulin analogs in intact and nephrectomized rats determined by their receptor binding constants.

After intravenous injection of 125I-labeled human insulin and analogs in normal and nephrectomized rats, we examined their kinetic fate by Q-Sepharose separation into intact ligand, "fragments" (genuine fragments and protein-bound radioactivity), and iodide. Receptor binding association and dissociation constants (kass and kdis, respectively) of the analogs were estimated dynamically in vitro by BIAcore. The very fast disappearance of intact ligand from serum was found to be determined by 1) both kass and kdis of receptor-bearing tissue, thus substantiating our primary hypothesis; 2) elimination by kidneys, and 3) fast extravascularization. The rate of appearance of degradation products from receptor-mediated intracellular processing seems determined by kdis. With the possible exception of a truncated analog, ligand appears protected against degradation while the intracellular receptor-ligand complex remains intact. Non-receptor-mediated processing in kidneys is slow, compared with the receptor-mediated uptake and degradation of ligands with rate constants comparable to those of insulin. We observed binding of insulin and analogs putatively to serum proteins; binding capacity and affinity appeared insignificant for insulin but considerable for some analogs.

Animals↗
PubMed1994

[Sclerosing cholangitis and ulcerative colitis. Regional prevalence].

The aim of the study was to determine the prevalence of primary sclerosing cholangitis (PSC) in a regional population of patients with ulcerative colitis (UC). Three hundred and five patients with UC followed over a 12 year period were examined for elevations of serum alkaline phosphatase (> 280 U/l). Twenty four such patients were found. If no cause of these elevations were found by initial investigations, endoscopic retrograde cholangiography was performed in order to determine whether they had PSC. Eleven patients were found to have PSC (3.6%), of whom five had progressive disease, including two deaths from cholangio-carcinoma, during a six-year observation period. We found no certain relation between the extent, duration or activity of ulcerative colitis and the presence of PSC. Alkaline phosphatases were elevated up to 3.7 times the upper reference level, the aminotransferases were only found to be mildly elevated.

Adolescent↗
PubMed1992

[Hepatocellular adenoma after oral contraception].

Raised serum basic phosphatase was found incidentally in a woman aged 43 years. Investigation with biopsy revealed a hepatocellular adenoma. The tumour regressed after withdrawal of Neogentrol oral contraception which the patient had consumed for 17 years. The patient did not desire invasive treatment. Employment of oral contraceptive steroids for more than two years is associated with increased occurrence of hepatocellular adenomata. The hepatocellular adenoma is a clearly delimited, most frequently solitary, benign tumour with limited malignant potential but with a considerable risk of rupture with haemorrhage even after withdrawal of oral contraception. The hepatocellular adenoma has no malignant tumour vessels (in contrast to hepatocellular carcinoma) and it appears as a cold region on scintigraphy (in contrast to focal nodular hyperplasia), but the diagnosis can only be established with certainty by histological examination. The hepatocellular adenoma consists most frequently of large pale hepatocytes in trabeculae surrounded by a net of reticulin and separated by sinusoids. Biliary passage and portal spaces do not occur. The best treatment consists of excision of the tumour or embolisation. If invasive treatment is postponed, regular scanning should be performed to observe regression or progression of the tumour and oral contraception and pregnancy should be advised against on account of the risk of growth of the tumour.

Adult↗
PubMed1992

Primary sclerosing cholangitis in patients with ulcerative colitis.

The prevalence of primary sclerosing cholangitis (PSC) in patients with ulcerative colitis (UC) attending the Depts. of Medical and Surgical Gastroenterology, Aalborg Hospital, during a 12-year period, was determined. All patients with an alkaline phosphatase (ALP) value above the normal range were investigated. Of 305 patients with UC, 24 patients had elevated ALP values, and 11 of these (3.6% of the study population), 4 males and 7 females, were found to have PSC by direct cholangiography. In five patients the disease worsened (two patients died of cholangiocarcinoma), in four it was stationary, and in two patients the disease improved during a mean observation period of 6 years. No differences in location of disease, disease activity, or duration of disease were found between patients with UC and PSC and patients with UC without PSC. The ALP values were raised to a mean of 3.7 times the upper normal limit (observed range, 1.5-5.5 times the upper normal limit). Aspartate aminotransferase was moderately elevated in most patients, but no other abnormal biochemical liver test results were observed at onset. The results of our study indicate that PSC is the major cause of raised ALP values in patients with UC; thus cholangiography should be performed in UC patients with unexplained elevated ALP levels. A prognostic indicator is needed to predict the individual prognosis and to determine the optimal timing of liver transplantation.

Adolescent↗
PubMed1991

Receptor binding and tyrosine kinase activation by insulin analogues with extreme affinities studied in human hepatoma HepG2 cells.

The insulin-receptor affinity of five human insulin analogues with one to four amino acid substitutions was measured with human hepatoma cells (HepG2). The binding affinities ranged from 0.05% for AspB25 insulin, 18% for AspB9, GluB27 insulin, 80% for AspB28 insulin, and 327% for AspB10 insulin to 687% for HisA8, HisB4, GluB10, HisB27 insulin relative to human insulin. Binding constants obtained by competition experiments at steady state with [125I]TyrA14-labeled insulin and unlabeled analogues and by kinetic studies with [125I]TyrA14-labeled analogues and insulin gave essentially the same values. The kinetic studies showed that differences in affinity between analogues were due to differences in both dissociation and association rate constants. The affinity for insulinlike growth factor I receptor was low, ranging from less than 0.005% for AspB25 insulin to 0.6% for HisA8, HisB4, GluB10, HisB27 insulin. The potencies of insulin analogues in activation of the tyrosine kinase of solubilized and partially purified insulin receptors from HepG2 cells, measured with the exogenous substrate poly(Glu80-Tyr20), ranked in the same order as the binding affinities, the actual values being somewhat elevated for the high-affinity analogues, however. We conclude that these human insulin analogues are active in insulin-receptor binding and tyrosine kinase stimulation but show wide variation in affinity.

Amino Acids↗
PubMed1991

Scintigraphic studies in rats. Kinetics of insulin analogues covering wide range of receptor affinities.

Whole-body kinetics of 123I-labeled human insulin and five insulin analogues were investigated by scintigraphic studies in rats. The amino acid substitutions and the relative receptor affinities (RAs), determined by binding to HepG2 cells, were: GluB12, des-B30 insulin, RA 0.15%; AspB9, GluB27 insulin, RA 18%; AspB26 insulin, RA 80%; AspB18 insulin, RA 327%; and HisA8, HisB4, GluB10, HisB27 insulin, RA 687%. All analogues were compared with human insulin (RA 100%). The analogue with RA 0.15% showed a significantly slower disappearance in the heart window, no liver uptake, and the greatest kidney radioactivity, the latter probably caused by high plasma concentrations. The low-affinity analogue (RA 18%) reached a surprisingly high hepatic peak value, although significantly lower than insulin. Kidney radioactivity was higher than for insulin. The analogue with RA 80% showed liver and kidney radioactivities that were not significantly different from those of insulin. The two high-affinity analogues (RAs 327 and 687%) showed peak liver radioactivities not significantly different from insulin. However, liver radioactivity after the peaks declined significantly more slowly. Compared with insulin, the kidney radioactivity curves were not significantly different. We conclude that high-affinity insulin analogues will bind to any available receptor that, because of the large number of receptors in the periphery and the distribution of cardiac output, favors extrahepatic elimination. In contrast, low-affinity analogues bind to receptors several times before they are eliminated. This leads to recirculation and, thus, hepatic elimination due to the high receptor density there. It follows that hepatopreferential binding cannot be expected solely by use of an insulin analogue with a particular receptor affinity.

Animals↗
PubMed1989

Systematic variation and differences in insulin-autoantibody measurements.

Insulin autoantibodies (IAAs) are currently the subject of intensive investigation as potential markers for autoimmune insulitis. However, the results of different reports vary widely. In an attempt to elucidate the reasons for the discrepant reports and to initiate standardization procedures, the International Diabetes Workshop (IDW) undertook two studies in which 22 centers worldwide measured IAA in coded samples. The variance in binding signal from the 49 sera in study 1 was considerable, even when results were standardized, but was largely systematic and attributable to basic differences in assay type (liquid phase versus solid phase) and to differences in the ligand used (human vs. nonhuman insulin). In study 2, 5 sera were prepared and presented blindly to compare dilution curves, insulin-species specificity, interference from irrelevant serum proteins, precision, and dose-dependent displaceability. Many assays, both liquid and solid phase, were influenced by marked and unpredictable nonspecific binding, revealed by loss of parallelism between dilution curves in pooled normal serum and buffer, by variable binding signals with different normal sera, and by difficulty in distinguishing human insulin-specific from cross-reactive IAA sera. It was concluded from the experience of both studies that variance could probably be reduced by using a standard curve with derived common units, a single species of ligand, and methodology to minimize the effect of nonspecific binding. Variation related to assay type was probably due to liquid- versus solid-phase systems being differentially more sensitive to certain aspects of antigen-antibody binding; this issue will be addressed in future serum exchanges and workshops.

Autoantibodies↗
PubMed1985

Effect of insulin antibodies on insulin pharmacokinetics and glucose utilization in insulin-dependent diabetic patients.

To determine the impact of insulin-binding antibodies on total (TIRI) and free insulin (FIRI) as well as on insulin sensitivity, 10 insulin-dependent diabetic patients (IDDM) with poststimulatory C-peptide less than 100 pmol/L and an insulin binding capacity (IBC) between less than 1 and 294 micrograms/L serum were studied during and after a 1-h nonprimed, constant-rate insulin infusion (study 1: 0.057 U/kg body wt, study 2: 0.286 U/kg body wt). Euglycemia was maintained by variable glucose infusion. Control studies were performed in 5 healthy subjects. Basal TIRI (mU/L) was lowest in healthy subjects (16 +/- 1 [SE]) and elevated in diabetic patients (IBC less than 25 micrograms/L: 72 +/- 11, IBC greater than 25 micrograms/L: 1772 +/- 842), whereas serum concentrations of FIRI were considerably smaller but still two- to threefold greater (P less than 0.01) in the patients than in healthy subjects (13 +/- 1). After intravenous (i.v.) insulin administration, almost identical increments in serum TIRI were seen in healthy subjects and in diabetic patients with low IBC (less than 25 micrograms/L), whereas those with high IBC (greater than 25 micrograms/L) had a heterogeneous response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

Human proinsulin standards.

Two new batches of pancreatic human proinsulin have been compared with biosynthetic human proinsulin. Standards of these three proinsulin preparations were made on the basis of quantitative amino-acid analyses and compared in two proinsulin radioimmunoassays with a proinsulin standard prepared 14 years ago. The curves of the new standards were superimposable. However, they differed considerably from the curve of the old standard which proved to be only one-third of the strength of the new standards, thereby leading to a threefold over-estimation of proinsulin concentrations when the old standard is used. We conclude that the new standards should replace previously used standards.

Amino Acids↗
PubMed1983

Pyeloureteral visualization using glucagon during intravenous urography.

194 adult patients were subjected to intravenous urography. In order to study the effect of glucagon on the visualization of the pyeloureteral system, IVU's were performed in four different ways: I. with abdominal compression, II. with glucagon 1 mg i.v., III. without abdominal compression and without glucagon, and IV, with abdominal compression and glucagon 1 mg. i.v. Coded objective and subjective analyses showed significant worsened visualization of the pyelocalyceal systems, when IVU was performed with glucagon alone. Ureteral visualization was equal to all four groups. Glucagon fails as a pharmacological alternative to abdominal compression in adult human subjects.

Female↗
PubMed1979

Dissociation rate constants and fractional binding of tracer estimated for three antibody populations in unstripped and stripped antiserum.

The dissociation rate constants of a high-affinity thyroxine antiserum were estimated on the basis of curves showing the dissociation of labelled thyroxine-antibody complexes as a function of time. The dissociation curves were fitted by computer to an equation with a sum of three exponentials. The analysis of the curves gave estimates of the dissociation rate constants for fast, medium and slowly dissociating antibody populations, and also estimates of the size of the fraction of tracer bound to each of the three populations of antibodies. The coefficients of variation for the estimates were of the order of 10%, and the estimates were reproducible. The dissociation rate constants for the thyroxine antibodies were 0.55, 0.045 and 0.0058 h-1 at 23 degrees C. When labelled thyroxine and antiserum were incubated for increasing periods of time, there was an increase in the fractional binding of tracer to the slow-dissociating antibodies. The use of stripped antiserum as against unstripped antiserum also improved the fractional binding of tracer to the slow-dissociating antibodies. The stripping effect was slight for three other antisera which contained relatively fast dissociating antibodies.

Animals↗
PubMed1979

Removal of endogenous ligands from a high-affinity antiserum for radioimmunoassay.

A method for removal of endogenous ligands from high-affinity antisera (stripping) is described. A thyroxine antiserum of very high affinity was used to develop the method. The antiserum was incubated at 50 degrees C in a glutamate buffer at pH 4.4 together with some ethanol and methyl cellulose and a large amount of activated charcoal. After incubation for up to 2 days, the stripped antibodies were separated from the ligand adsorbed to the charcoal by centrifugation. The estimated titre increased several fold by the stripping, although the stripping method caused a loss of about 13% of the total number of binding sites over a period of 2 days. When stripped antiserum was used instead of unstripped antiserum in an assay system, the sensitivity was up to 3 times better, and the concentration, which could be measured with the best relative precision, was 3 times lower. The stripped antiserum showed a poorer specificity than the unstripped antiserum when a short incubation period was used. However, when a long incubation period was used, the specificity was nearly the same.

Adsorption↗
PubMed1979

Oxytocin determination by radioimmunoassay in cattle. I. Method and preliminary physiological data.

A radioimmunoassay for oxytocin in cow plasma is described. Antisera were raised in rabbits against synthetic oxytocin coupled to bovine thyroglobulin. Iodinated oxytocin free of unlabelled oxytocin and most likely also free of diiodo-oxytocin was used as radioactive tracer. The tracer showed a high degree of purity, and was stable on storage. It could be used in the assay for 2--3 months. The assay showed very little cross-reactivity with vasopressin. Acetone was used for the extraction of oxytocin from plasma as well as from standards made of synthetic oxytocin in pooled cow plasma. Inhibition curves obtained with plasma collected from cows at parturition were parallel to those obtained with the oxytocin standard preparation. The mean recovery of oxytocin added to cow plasma was 106% (SD = 14). The within-assay coefficient of variation (CV) varied from 5.2 to 10.9%, and the between-assay CV was in the order of 13%. The assay sensitivity was 1 pg (0.5 uU) per tube, corresponding to 3 pg/ml plasma. Around the time of milking the plasma oxytocin profile showed a strong response to the preparation for milking, and a further effect releated to the attachment of the teat cups of the milking machine. Peak concentrations were in the range of 15--50 pg/ml. During parturition there was a peak of oxytocin (65 pg/ml) coinciding with the expulsion phas. After this peak levels decreased but remained measurably elevated until the expulsion of the placenta. The plasma disappearance curve for immunoreactive oxytocin after the infusion of 100 IU oxytocin over a period of 1 h showed two components with apparent half-lives of 7--7 and 25 min, respectively.

Animals↗
PubMed1978

The effect of nonfractionated and fractionated administration of iopanoic acid on gallbladder visualization.

Visualization of the gallbladder after nonfractionated and fractionated administration of iopanoic acid was investigated in a blind experiment. The authors studied 168 patients; 73 were given 3 g iopanoic acid over a period of 6 hours (0.5 g/hour), and 95 received the same amount of contrast medium in a single dose. No differences in visualization were found for the two modes in both normal and pathological cases.

Cholecystography↗
PubMed1977

A rapid and precise sequential saturation radioimmunoassay for thyroxine.

A radioimmunoassay for the measurement of total thyroxine in unextracted serum or plasma is described. The assay is performed according to the sequential saturation principle in less than 4 h. The entire assay is carried out at room temperature. An antiserum of high affinity was used as binder, ammonium 8-anilino-1-naphthalene-sulphonate as displacing agent, and activated charcoal as adsorbent in the separation step. The standard curve was linear in the range 0-136 nmol/l serum. The precision in terms of SD was nearly the same through-out this range. Estimates of within-assay SD varied from 1.3 to 4.1 and between-assay SD from 0 to 3.3 nmol/l. The recovery of thyroxine added to normal plasma was 100% and the sensitivity was 6 nmol/l. Mean thyroxine concentration in plasma from young bulls was 92 nmol/l. The assay appears to be very well suited for experimental purposes when high precision is essential.

Animals↗