Biomedical subjects

S Fisker

Publications and source records attributed to S Fisker.

46 records · Page 3Linked to original sources

PubMed1996

Decreased plasma and extracellular volume in growth hormone deficient adults and the acute and prolonged effects of GH administration: a controlled experimental study.

OBJECTIVE: There are few data on the endocrine mechanisms underlying the body fluid changes in GH deficiency and their subsequent alteration following GH replacement. We have therefore investigated the time effects of GH on body fluid distribution and fluid regulating hormones in GH deficient adults. DESIGN: The patients underwent in random order four study periods: (1) saline, a 42-hour infusion following 3 weeks without GH, (2) acute GH, a 42-hour GH infusion following 3 weeks without GH, (3) 3 days GH, a 42-hour GH infusion preceded by 3 weeks without GH and 3 days pretreatment with subcutaneous GH injections, (4) 3 weeks GH, a 42-hour GH infusion after at least 3 weeks GH therapy. SUBJECTS: Seven GH deficient adult males and 8 healthy control subjects. MEASUREMENTS: During each infusion period 24-hour blood pressure was recorded, bioimpedance was repeatedly measured and blood samples were obtained every 6 hours. After 41 hours extracellular and plasma volumes were determined isotopically. Extracellular volume, plasma volume and bioimpedance were measured in the control group. RESULTS: GH increased extracellular volume (saline 16.45 +/- 0.79 vs acute GH 16.83 +/- 0.87; vs 3 days GH 17.58 +/- 0.71; vs 3 weeks GH 17.92 +/- 0.88 l, P = 0.01). After 3 weeks of GH, extracellular volumes in the patients and in the control group were identical (control 17.94 +/- 0.32). Plasma volume was increased only after 3 weeks GH treatment (saline 2.93 +/- 0.16 vs acute GH 3.04 +/- 0.22; vs 3 days GH 3.06 +/- 0.07; vs 3 weeks GH 3.37 +/- 0.18 l, P = 0.03), and was decreased compared to the control group (control 3.56 +/- 0.03 l, P < 0.01). Bioimpedance decreased significantly in all treatment periods and was significantly increased compared to the control group. Plasma renin increased during GH administration (saline 16.2 +/- 1.9 vs acute 19.0 +/- 1.9; vs 3 days GH 30.8 +/- 3.0; vs 3 weeks GH 27.0 +/- 3.0 mU/l, P = 0.03), whereas aldosterone and atrial natriuretic factor (ANF) levels remained unaffected by GH. GH caused an increase in systolic blood pressure (BP) and heart rate, whereas diastolic BP remained unaffected. CONCLUSIONS: The present data show that GH deficiency is associated with decreased plasma volume and extracellular volume. GH exposure acutely increases extracellular volume, whereas substitution for a longer time was required to normalize both extracellular and plasma volumes. Renin seems to be involved in these fluid volume regulating effects of GH.

Adult↗

PubMed1996

A simple, rapid immunometric assay for determination of functional and growth hormone-occupied growth hormone-binding protein in human serum.

We present a sensitive time-resolved fluorometric immunofunctional assay (TR-FIA) for direct quantitation of functional growth hormone-binding protein (GHBP), using an immunoassay kit for growth hormone (GH-DELFIA). In addition to the immobilized GH antibody, one monoclonal antibody against GHBP was used. This anti-GHBP was labelled with the chelate of europium. The assay was performed in one step. The detection limit for GHBP was 0.044 nmol L-1 (NBS + 3 SD). The calibration curve was linear in the interval 0.11-8.03 nmol L-1. Average intra-assay coefficient of variation (CV) was 3.44%. Average interassay CV at GHBP concentrations 0.563 nmol L-1 and 1.40 nmol L-1 were 12% and 6.3% respectively. Analytical recovery in serum ranged from 76% to 127% with a mean of 101 +/- 3.6%. Serum GHBP in 102 normal subjects ranged from 0.513 to 3.772 nmol L-1 and was positively related to body mass index (P < 0.001). In growth hormone-deficient sera GHBP was higher than in control subjects (1.751 +/- 0.179 nmol L-1 and 1.257 +/- 0.140 nmol L-1 respectively, P < 0.001). Acromegalic patients had lower levels of GHBP than controls (0.946 +/- 0.251 and 1.234 +/- 0.144 nmol L-1 respectively, P = 0.005). This assay also allowed detection of GH-complexed GHBP in serum. These results were in agreement with theoretical values calculated from the measured GH and the functional GHBP concentrations. Results were compared with data obtained by a recently reported, validated ligand immunofunctional assay (LIFA), which is fundamentally different. There was a significant linear relationship between the results from the two assays (r = 0.89, P = 0.001). The slope of the regression line was 0.65. In conclusion, this new convenient GHBP TR-FIA provides a sensitive and precise method for detecting total GHBP as well as complexed GHBP in human serum, and allows easy processing of large numbers of samples.

Acromegaly↗

PubMed1996

Influence of growth hormone and androgens on body composition in adults.

The secretion of both growth hormone (GH) and androgens declines with age which may play a role in the senescent changes in body composition and organ function. Among healthy adults abdominal adiposity is an important negative determinant of GH secretion. Surprisingly, abdominal or android obesity seems inversely correlated with testosterone levels in males but not in females. The ability of GH to promote lipolysis and preserve or increase lean body mass has been reappraised in substitution studies in GH-deficient adults. By comparison, adequately controlled studies of androgen replacement in hypogonadal and/or elderly males are few. In view of the physiological and clinical relevance of obtaining information about the aging process, there is a need for controlled experiments addressing similarities and differences between the action of GH and sex steroids in adults.

Adult↗

PubMed1996

Factors modifying growth hormone estimates in immunoassays.

Growth hormone (GH) in human serum has been measured for more than 30 years and during this period it has been used diagnostically in growth disturbances and GH disorders. The first GH determinations were by radioimmunoassays using polyclonal antibodies. Due to the low specificity of these assays and the variable molecular appearance of GH, higher levels were obtained than with later assays employing two highly specific monoclonal antibodies. Because of this variability between assays, empiric GH cutoff levels had to be developed in different laboratories. However, with the growing need for more sophisticated diagnosis, especially in adulthood GH deficiency, knowledge of factors influencing the individual GH assays is required. Since GH deficiency in adulthood is now treated with GH substitution therapy, the relevance of factors influencing GH estimates has become increasingly evident, because no specific symptoms exist in adult GH deficiency.

Adult↗

PubMed1995

Fuel metabolism in growth hormone-deficient adults.

Apart from being a stimulator of longitudinal growth, growth hormone (GH) regulates fuel metabolism in children and adults. A halfmark is mobilization of lipids, which involves an inhibition of lipoprotein lipase activity in adipose tissue and activation of the hormone sensitive lipase. Suppression of basal glucose oxidation and resistance to insulin are other important effects. This may cause concern during GH substitution in GH-deficient adults, some of whom may present with insulin resistance due to concomitant abdominal obesity. However, there are data to suggest that the GH-induced reduction in fat mass and increase in lean body mass may offset the insulin antagonistic actions of the hormone. The nitrogen-retaining effects of GH seem to involve a direct stimulation of protein synthesis in addition to secondary effects such as generation of insulin-like growth factor-I (IGF-I), hyperinsulinemia, and promotion of lipolysis. Thus, during periods of substrate affluence, GH acts in concert with insulin and IGF-I to promote protein anabolism. Postabsorptively, GH is primarily lipolytic and thereby indirectly protein-sparing. This effect becomes further accentuated with more prolonged fasting. In that sense, GH is unique by its preservation of protein during both feast and famine. These fuel metabolic effects add merit to the principle of GH substitution in hypopituitary adults.

Adult↗

PubMed1992

In vivo inflammatory stimulation induces a transient change in the binding of thrombin to rat peritoneal macrophages.

The binding of 125I-labeled thrombin to rat peritoneal macrophages isolated 20 h after the ip injection of thioglycollate broth or lipopolysaccharide decreased to 20% of the value found in resident macrophages due to a decrease in the number of receptors. The binding returned to normal values within a week after the injection. The decline parallelled more or less the Vmax for the 5'-nucleotidase activity. This decrease in the binding of thrombin could not be explained by an immigration of monocytes into the peritoneal cavity, since the binding of 125I-labeled alpha 2-macroglobulin-trypsin complex increased 4.5-fold in the same cell population due to an increase in the number of receptors, and blood monocytes do not bind alpha 2-macroglobulin-trypsin complex. The increase in the binding of alpha 2-macroglobulin-protease complex parallelled an increase in the incorporation of glucosamine, although the latter did not increase to the same extent. Engulfment of plasma membrane after phagocytosis did not result in a decreased binding of thrombin, but preincubation at 37 degrees C with concanavalin A caused a minor reduction in the binding. There was a positive correlation between the binding of alpha 2-macroglobulin-trypsin complex and the fraction of polymorphonuclear leukocytes in the peritoneal exudate and a negative correlation between the binding of thrombin and the fraction of polymorphonuclear leukocytes in the exudate, when the inflammation was induced by a milder stimulus, sterile NaCl, indicating a common signal for the polymorphonuclear leukocyte chemotaxis and the macrophage differentiation.

Animals↗

PubMed1991

A thrombin receptor in resident rat peritoneal macrophages.

Resident rat peritoneal macrophages possess 6 x 10(2) high-affinity binding sites per cell for bovine thrombin with a Kd of 11 pM, and 7.5 x 10(4) low-affinity sites with a Kd of 5.8 nM. These binding sites are highly specific for thrombin. Half-maximal binding of 125I-labeled bovine thrombin is achieved after 1 min at 37 degrees C, and after 12 min at 4 degrees C. The reversibly bound fraction of the ligand dissociates according to a biexponential time course with the rate constants 0.27 and 0.06 min-1 at 4 degrees C. Part of the tracer remains cell-associated even after prolonged incubation, but all cell-associated radio-activity migrates as intact thrombin upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The bound thrombin is minimally endocytosed as judged by the resistance to pH 3 treatment, and the receptor does not mediate a quantitatively important degradation of the ligand. The binding is not dependent on the catalytic site of thrombin, since irreversibly inactivated thrombin also binds to the receptor. 125I-labeled thrombin covalently cross-linked to its receptor migrates in sodium dodecyl sulfate-polyacrylamide gel electrophoresis with a Mr 160,000, corresponding to an approximate receptor size of Mr 120,000.

Amino Acid Sequence↗

PubMed1991

A rapid microtitration plate assay for non-specific esterase.

A simple and convenient colorimetric assay for the quantification of non-specific esterase is described. The assay takes advantage of the microtitration plate format, and the high capacity of repetitive dispensers and the microplate reader for this format. The assay is well suited for the quantification changes in the esterase activity in homogeneous cell populations like monocytes maturing into macrophages.

Animals↗

PubMed1990

Isolation of rat peritoneal mononuclear and polymorphonuclear leucocytes on discontinuous gradients of Nycodenz.

Centrifugation of rat leucocytes from thioglycollate-induced inflammatory peritoneal exudate on a discontinuous gradient of Nycodenz with a density of 1106 g/l and an osmolarity of 400 mosmol/l separated the polymorphonuclear from the mononuclear leucocytes. The cells on the interphase between the buffer and the gradient medium contained 96% mononuclear leucocytes with a recovery of greater than 60%, and the bottom fraction consisted of 98% polymorphonuclear leucocytes with a yield of 91%, when an exudate isolated 20 h after the injection of thioglycollate was fractionated. Leucocytes isolated from non-inflamed rat peritoneum could be enriched in the fraction of nonspecific esterase-positive cells from 86% to 96% with a recovery of 82% on a gradient with a density of 1091 g/l and an osmolarity of 325 mosmol/l. The viability of the isolated cells was greater than 95% (trypan blue exclusion test), and there was no measurable reduction in the fraction of phagocytosing cells (latex and opsonized zymosan) after exposure to the hypertonic gradient material.

Animals↗

PubMedDate not supplied

Circulating levels of free insulin-like growth factors in obese subjects: the impact of type 2 diabetes.

BACKGROUND: Obese subjects show major abnormalities in the growth hormone (GH)/insulin-like growth factor (IGF) system. Furthermore, they are prone to develop Type 2 diabetes, but the impact of diabetes plus obesity on the GH/IGF system remains unknown. METHODS: We compared overnight fasting serum levels of free and total (extractable) IGF-I and -II, IGF-binding protein (IGFBP) -1, -2 and -3, and the high affinity GH-binding protein (GHBP) in matched groups of lean subjects (n=26) and obese subjects without (n=24) and with (n=29) Type 2 diabetes. Two groups (n=7) of healthy and Type 1 diabetic subjects were also studied. RESULTS: Non-diabetic obese subjects had increased free IGF-I and -II, total IGF-II, IGFBP-3 and GHBP, reduced IGFBP-1 and -2 (p<0.05), but normal total IGF-I, when compared to lean subjects. In obese Type 2 diabetics free IGF-I was insignificantly reduced by 9% (p=0.3), when compared to non-diabetic obese subjects. However, the concentration was not significantly elevated when compared to that of lean controls (p=0.13). Also IGFBP-1 and total IGF-I were normal in obese Type 2 diabetics, whereas free and total IGF-II and IGFBP-3 remained elevated to a similar extent as in simple obesity (p<0.05). In contrast, GHBP was further increased and IGFBP-2 further reduced in obese Type 2 diabetics (p<0.05). In Type 1 diabetics total IGF-I and -II, and IGFBP-3 were normal. In contrast, free IGF-I and -II and GHBP were markedly reduced, whereas IGFBP-1 and -2 were increased (p<0.05). CONCLUSIONS: Simple obesity was associated with marked changes in the GH/IGF system. Many of these abnormalities were unaffected by the concomitant presence of Type 2 diabetes (total IGF-I, free and total IGF-II and IGFBP-3). However, some changes became accentuated (GHBP and IGFBP-2), while others (free IGF-I and IGFBP-1) were no longer present. Notably, the impact of Type 1 diabetes on the GH/IGF system was clearly different from that of Type 2 diabetes.

Analysis of Variance↗