Islet-amyloid polypeptide in human plasma.
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Amyloid↗
Biomedical subjects
W H Hackeng
Publications and source records attributed to W H Hackeng.
Cholesterol metabolism, digestion rates and postprandial changes in serum of swine fed purified diets containing either casein or soybean protein.
Swine fitted with re-entrant ileo-cecal cannulas were fed purified diets containing either casein or soybean protein to study possible relations between cholesterol metabolism, digestion of dietary constituents and postprandial patterns of various serum components. Compared with soybean protein, dietary casein produced an increase in serum total cholesterol in which the excess cholesterol was located in the low density lipoprotein fraction. Ileal and fecal excretion of neutral steroids was diminished in pigs fed casein, suggesting that cholesterol absorption was stimulated. The apparent ileal absorption of protein was increased in pigs fed casein. The enhanced absorption of cholesterol and protein was associated with a reduced rate of flow of chyme through the ileum. The output of bile acids in the feces of pigs fed casein was decreased, whereas the ileal output was not significantly affected. This could be attributed to increased uptake of bile acids from the cecum and/or colon, which may in part be related to the indirectly observed decreased formation of secondary bile acids. Postprandial serum concentrations of insulin and glucose were temporarily increased in pigs fed casein, whereas those of triglycerides were decreased. We suggest that the decreased excretion of cholesterol and bile acids is the major determinant of casein-induced hypercholesterolemia in swine.
Animals↗
Excessive secretion of antidiuretic hormone in infections with respiratory syncytial virus.
The association between infections with respiratory syncytial virus and plasma concentrations of antidiuretic hormone was assessed in 48 patients who had been admitted to hospital. The mean (SEM) concentration of antidiuretic hormone was significantly raised in patients with bronchiolitis (9.3 (1.4) ng/l) compared with non-pulmonary respiratory syncytial virus infections that cause apnoea or upper respiratory tract symptoms (6.1 (1.7) ng/l). The highest concentrations of antidiuretic hormone were seen in patients receiving mechanical ventilation (18.0 (6.7) ng/l). There were no differences in mean serum sodium concentrations among the subgroups. Hypertranslucency on chest radiograph or an arterial carbon dioxide tension above 6.67 kPa were associated with a significantly higher concentration of antidiuretic hormone. Increased or normal maintenance fluid intake in children with pulmonary respiratory syncytial virus infections may cause the same symptoms of fluid overload as the syndrome of inappropriate secretion of antidiuretic hormone. Patients with pulmonary respiratory syncytial virus infection, hypertranslucency in chest radiograph, hypercapnia, or mechanical ventilation are at risk for raised concentrations of antidiuretic hormone. Restricted fluid intake and careful monitoring of fluid balance and plasma electrolyte concentrations are therefore necessary in these patients.
Bronchiolitis, Viral↗
Evidence for the involvement of corticotropin-releasing factor in the inhibition of gonadotropin release induced by hyperprolactinemia.
The hypothesis was tested that corticotropin-releasing factor (CRF) is involved in the inhibition of gonadotropin secretion during chronic hyperprolactinemia. Two models of hyperprolactinemia were used, namely inoculation with the prolactin (PRL)-secreting tumor 7315b and implantation of isogenic pituitary glands. Gonadectomized, adrenalectomized male rats received a testosterone capsule and a corticosterone pellet and were inoculated subcutaneously with tumor 7315b. Similar rats without tumor served as controls. The rats were studied 3-4 weeks later while anesthetized with urethane. Plasma testosterone and corticosterone were similar in the two groups of rats. Compared to controls, the tumor-bearing rats had significantly higher plasma levels of PRL (100-fold increase) and adrenocorticotropin (ACTH; 3-fold increase), whereas plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) had significantly decreased to 15 and 40%, respectively. CRF release into hypophysial stalk plasma was higher in rats with tumor 7315b than in controls (298 +/- 23 vs. 197 +/- 28 pg/h), and hypothalamic CRF content had increased from 3.0 +/- 0.3 to 4.3 +/- 0.3 ng. Male rats received 3 pituitary glands under the kidney capsule. Sham-operated rats served as controls. They were studied 5-7 weeks later while anesthetized with urethane. Compared to controls, pituitary-grafted rats had larger adrenals (49 +/- 4 vs. 34 +/- 2 mg), higher plasma PRL (156 +/- 18 vs. 52 +/- 8 ng/ml), ACTH (0.46 +/- 0.05 vs. 0.22 +/- 0.02 ng/ml) and corticosterone (455 +/- 39 vs. 268 +/- 14 ng/ml), and lower plasma levels of LH (21 +/- 2 vs. 41 +/- 6 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenalectomy↗
Twenty-four-hour plasma growth hormone (GH) profiles, urinary GH excretion, and plasma insulin-like growth factor-I and -II levels in prepubertal children with chronic renal insufficiency and severe growth retardation.
We studied 24-h plasma GH profiles, maximal GH responses to arginine provocation and insulin-like growth factor-I (IGF-I) and IGF-II levels in plasma in 22 euthyroid prepubertal children (mean age, 9.5 yr) with chronic renal insufficiency (glomerular filtration rate, less than 20 mL/min.1.73 m2) and severe growth retardation [mean (+/- SD) height SD score (SDS), -2.8 (1.1)]. The 24-h GH profiles were analyzed using the Pulsar program. Girls had significantly higher 24-h GH secretion than boys (P less than 0.004). Children with end-stage nephrotic syndrome had higher baseline GH levels and total area under the curve (AUCo) than patients with dysplastic kidneys (P less than 0.05), while the area under the curve above baseline (AUCb) was similar in all types of renal diseases. The type of treatment (conservative, peritoneal, hemodialysis) did not significantly influence the 24-h GH secretion. No correlation was found between 24-h GH profiles and age, height SDS for chronological age, height velocity SDS for bone age, and weight for height. Fourteen children showed a normal 24-h GH profile, defined as a GH profile with well defined, regular GH peaks returning to baseline GH levels and a distinct day and night pattern (AUCb, 90-300 micrograms/L.24 h). Four children had low profiles, with GH peaks below 10 micrograms/L, returning to baseline GH levels and occurring almost exclusively during the night (AUCb, less than 90 micrograms/L.24 h). The remaining four children had elevated 24-h GH profiles, with GH peaks on top of elevated baseline GH levels of more than 3 micrograms/L (AUCb, 35-205 micrograms/L.24 h; AUCo greater than 300 micrograms/L.24 h). In all patients 24-h urinary GH and beta 2-globulin excretion was 100-1000 times higher than that in controls. The urinary GH excretion correlated significantly with all characteristics of the 24-h GH profiles (r = 0.57-0.59; P less than 0.05). The maximal GH response during the arginine tolerance test was normal in 66% of the children. The mean (+/- SD) SDS for bone age for the IGF-I plasma levels was +1.1 (1.9), and that for IGF-II was +3.6 (3.4). IGF-I levels correlated significantly with the AUCb, maximum GH, and GH peak characteristics of the 24-h GH profiles (r = 0.05-0.73; P less than 0.02-0.001). IGF-II levels did not show any correlation with the characteristics of the endogenous GH secretion.(ABSTRACT TRUNCATED AT 400 WORDS)
Adolescent↗
Lack of evidence for autocrine feedback regulation by somatostatin in somatostatin receptor-containing meningiomas.
The somatostatin (SS), the SS mRNA, and the SS receptor contents were measured and compared in 25 human meningiomas. The SS tissue content, measured with radioimmunoassay, amounted to 2.89 +/- 0.82 pg/mg tissue (mean +/- SEM). The SS mRNA levels visualized by in situ hybridization using a 32P-labeled synthetic oligonucleotide probe were undetectable in all cases. SS receptors were measured with autoradiography using the octapeptide SS analogue 125I-204-090 as radioligand and were found to be present in high density in all meningiomas. For comparison, three SS-producing tumors, i.e., two human medullary thyroid carcinomas and one neuroendocrine gut tumor, were shown to have a high level of immunoreactive tissue SS, reaching, respectively, 2807, 401, and 22 pg/mg tissue, as well as moderate to high levels of SS mRNA detected with in situ hybridization. It can be concluded that meningioma tissue is not synthesizing significant amounts of SS in situ and that the low amount of tissue SS found in these tumors is likely to be due to SS transported there from a distant source, via blood, cerebrospinal fluid, or axons from nerve fibers terminating in this tissue. The high number of SS receptors found in meningiomas is therefore unlikely to be regulated by an autocrine SS production from the meningioma tissue itself but rather from another, unknown distant SS source.
DNA Probes↗
The usefulness of an oral calcium tolerance test in the choice of management of patients with idiopathic hypercalciuria.
We studied 40 patients with calcium urolithiasis and idiopathic hypercalciuria in an attempt to identify patients with an absorptive or renal type of hypercalciuria. An oral calcium tolerance test was performed in all patients, resulting in a rise in serum calcium in all cases (2.35 +/- 0.09 mmol/l vs 2.49 +/- 0.09 mmol/l; P less than 0.001). This was also true for serum phosphate (0.96 +/- 0.17 mmol/l vs 1.09 +/- 0.18 mmol/l; P less than 0.001), TmPO4/GFR (0.95 +/- 0.19 mmol/l vs 1.20 +/- 0.25 mmol/l; P less than 0.001) and fasting calcium excretion (3.14 +/- 1.16 mmol/100 l GF vs 6.17 +/- 2.02 mmol/100 l GF; P less than 0.001). All patients showed a drop in nephrogenous cAMP excretion (1.33 +/- 0.95 nmol/dl GF vs 0.74 +/- 0.72 nmol/dl GF; P less than 0.001). iPTH levels declined significantly (2.70 +/- 1.50 pmol/l vs 2.11 +/- 1.19 pmol/l; P less than 0.001). However, discordant individual changes in suppression of nephrogenous cAMP excretion, and rises in fasting calcium excretion prohibited a distinction between the absorptive or renal type of hypercalciuria. It is concluded that an oral calcium tolerance test is not helpful in the choice of management of patients with idiopathic hypercalciuria.
Administration, Oral↗
Identifying patients with incipient diabetic nephropathy. Should 24-hour urine collections be used?
It is not clear whether 24-hour or overnight urine collections should be used to identify patients with incipient diabetic nephropathy (defined as persistent urinary albumin excretion rate [AER] of 20 to 200 micrograms/min). We therefore studied diurnal variations in AER in type I diabetics with normal AER (n = 16) and incipient (n = 12) and clinical (defined as persistent AER greater than 200 micrograms/min) nephropathy (n = 12), and in healthy controls (n = 24). In all groups AER was lowest at night. In some patients of all groups, marked diurnal variations were observed. Twenty-four-hour urine collections classified all patients correctly. Overnight urine collections, however, misclassified patients with incipient nephropathy as having normal AER in 4 of 12, 7 of 12, or 3 of 7 cases, depending on which cutoff level was used. We conclude that 24-hour urine collections are more sensitive than overnight samples in identifying patients with incipient diabetic nephropathy.
Adult↗
Change of serum calcitonin in patients receiving glucocorticoids: an acute phase study.
The basal and calcium-stimulated calcitonin response was measured in 10 patients with giant cell arteritis before and 1, 3 and 6 wk after the start of daily treatment with 60 mg of prednisone. The study shows that plasma calcitonin level in response to a calcium injection is increased after 1 wk treatment with prednisone. Later on the calcitonin secretion capacity diminishes significantly compared to the initial level. The phylogenetic old calcitonin system first tries to prevent the occurrence of the process of osteoporosis. Moreover, exhaustion of this system later contributes to the process of steroid osteoporosis.
Acute Disease↗
Total deficiency of growth hormone and prolactin, and partial deficiency of thyroid stimulating hormone in two Dutch families: a new variant of hereditary pituitary deficiency.
Four out of 10 children in two unrelated families presented with a total pituitary growth hormone (GH) and prolactin deficiency and a partial thyrotropin (TSH) deficiency. The GH gene was intact in family I. The pituitaries, visualized by magnetic resonance imaging, were normal. All children responded well to GH and L-thyroxine therapy. Baseline plasma somatostatin and its peak response to arginine infusion were elevated in family I and they had a milder TSH deficiency than family II. Plasma insulin showed a poor response to arginine infusion. This hereditary combination of pituitary deficiencies suggests a deficiency of a common positive transcription factor.
Adult↗
Vitamin D metabolism in breast-fed infants and their mothers.
The aim of this longitudinal study was to examine vitamin D metabolism in exclusively breast-fed infants. The four common vitamin D metabolites--25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D [1,25(OH)2D], 24,25-dihydroxyvitamin D [24,25(OH)2D], and 25,26-dihydroxyvitamin D [25,26(OH)2D]--as well as vitamin D binding protein (DBP) were determined simultaneously in mothers and their children from delivery to several months of age. Maternal blood samples, drawn approximately 6 wk before the expected date of delivery, were also analyzed. At delivery, total vitamin D metabolites in maternal and fetal plasma were closely correlated, maternal levels being higher. Unbound (free) vitamin D metabolite concentrations were higher in fetal than in maternal plasma, with the exception of free 1,25(OH)2D levels, which were equal. This suggests a rapid placental transfer of 1,25(OH)2D. 24,25(OH)2D and 25,26(OH)2D levels both in mothers and children were closely correlated with the precursor sterol 25OHD. For 1,25(OH)2D, no correlation could be demonstrated with any of the other vitamin D metabolites. DBP concentrations in maternal plasma at the time of delivery were about twice the mean adult reference value. In cord blood, DBP levels were in the lower part of the adult reference range. Maternal total 1,25(OH)2D levels, which were twice the reference mean during pregnancy, fell sharply after delivery but free 1,25(OH)2D levels much less. Analogous to the biochemical changes in the mother, the infants' DBP levels fell after birth, as a result of the sudden disappearance of the estrogen stimulus. At the same time, the mineral supply via the placenta was cut off.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
The new aromatase inhibitor CGS-16949A suppresses aldosterone and cortisol production by human adrenal cells in vitro.
CGS-16949A is a new orally active nonsteroidal aromatase inhibitor which is more than 100-fold more potent than aminoglutethimide. This compound is an imidazole derivative, and therefore, its possible effect on cytochrome P-450-dependent enzyme activities in the adrenal gland was evaluated. In vitro investigations with dispersed normal and hyperplastic human adrenocortical cells showed that CGS-16949A at 10(-7)-10(-6) M is a potent 11 beta-hydroxylase inhibitor, which inhibits ACTH-stimulated cortisol release to a similar extent as an equimolar concentration of metyrapone (IC50 for both compounds, 10(-7)-5 X 10(-7) M). Etomidate was a more potent 11 beta-hydroxylase inhibitor (IC50, approximately 10(-8) M), while 10(-7)-10(-6) M ketoconazole caused (via 17 alpha-hydroxylase inhibition) a similar inhibition of cortisol release as 10(-7) M CGS-16949A (IC50, 10(-7)-5 X 10(-7) M). The 11 beta-hydroxylase inhibition by CGS-16949A was accompanied by a dose-dependent increase in the release of precursor steroids by the adrenocortical cells in vitro, including deoxycortisol, 17-hydroxyprogesterone, and androstenedione. Aldosterone release was suppressed 50% by 10(-9) M CGS-16949A, while the IC50 for cortisol in the same cells was 10(-7) M. Aldosterone release by the dispersed adenoma cells obtained from a patient with primary aldosteronism was also significantly suppressed by CGS-16949A. We concluded that 1) the new nonsteroidal aromatase inhibitor CGS 16949A is an inhibitor of 11 beta-hydroxylase which is equipotent to metyrapone. At present it is unclear whether the compound at the dose that causes complete aromatase inhibition in vivo also affects stress-induced cortisol release in man. 2) CGS-16949A exerts a very potent inhibitory effect on normal aldosterone release (IC50, 10(-9) M) and on tumorous aldosterone secretion. CGS-16949A might, therefore, be a drug that can be used in the treatment of primary hyperaldosteronism.
Adrenal Cortex↗
Aggravation of hypoglycemia in insulinoma patients by the long-acting somatostatin analogue octreotide (Sandostatin).
Recently somatostatin analogues were successfully used to control insulin-induced hypoglycemia in patients with insulinoma. We observed a transient decrease in glucose levels and symptomatic hypoglycemia after administration of the long-acting somatostatin-analogue octreotide (Sandostatin) in two insulinoma patients. We studied the acute effects of octreotide (administered before breakfast) on blood glucose and gluco-regulatory hormones in these patients. In one patient, we studied the effects of glucagon replacement and changing the time of breakfast (relative to octreotide administration) on octreotide-associated changes in blood glucose and glucoregulatory hormones. Compared with control levels, octreotide therapy reduced insulin levels. During hypoglycemia glucagon and growth hormone levels were suppressed, but cortisol levels appropriately increased. The increase in catecholamine levels was normal in one patient, but markedly attenuated in the other. A transient decrease in serum glucose after octreotide was absent after glucagon replacement, but present when breakfast was taken before administration of octreotide. We conclude that in patients with insulinoma, octreotide therapy may be associated with clinically important hypoglycemia, during which counterregulatory hormone secretion may be attenuated.
Adenoma, Islet Cell↗
Malignant insulinoma: is combined treatment with verapamil and the long-acting somatostatin analogue octreotide (SMS 201-995) more effective than single therapy with either drug?
The efficacy of treatment with either verapamil (V), the long-acting somatostatin analogue octreotide (OCT) alone, and the combined treatment (V + OCT) were studied in a patient with a symptomatic metastasized malignant insulinoma. Treatment with V alone resulted in a slight increase in blood glucose levels. Treatment with OCT alone resulted in a clear increase in blood glucose levels. Treatment with V + OCT was slightly more effective than single therapy with either drug but could not prevent hypoglycaemic episodes completely. It is also shown that the effect of treatment with V and OCT alone on glucoregulatory hormones is completely different. While treatment with V did not inhibit insulin secretion, treatment with OCT clearly did. Treatment with OCT might also modify counterregulatory hormone secretion during hypoglycaemia.
Adenoma, Islet Cell↗
Raised plasma intact parathyroid hormone concentrations in young people with mildly raised blood pressure.
To study the role of parathyroid gland activity in early primary hypertension plasma concentrations of intact parathyroid hormone were measured in 90 untreated young subjects, aged 16-29, with stable midly raised blood pressure and in 40 normotensive control subjects selected from the same population in Zoetermeer, The Netherlands. Intact parathyroid hormone concentration was significantly higher in the hypertensive than the normotensive group (2.34 (SE 0.11) pmol/l v 1.47 (0.13) pmol/l, respectively; difference 0.87 pmol/l; 95% confidence interval 0.55 to 1.21; p less than 0.0001). Serum total calcium concentration was 2.36 (0.01) mmol/l in the hypertensive group and 2.42 (0.01) mmol/l in the normotensive group (difference 0.06 mmol/l; 95% confidence interval 0.02 to 0.09; p = 0.02). Urinary calcium excretion over 24 hours did not differ significantly between the two groups (4.17 (0.28) mmol/24 h in the hypertensive group and 3.89 (0.39) mmol/24 h in the normotensive group; difference 0.28 mmol/24 h; 95% confidence interval -0.66 to 1.22). In the hypertensive group both systolic and diastolic blood pressures increased slightly though significantly with intact parathyroid hormone concentrations. No obvious associations between serum calcium concentration and blood pressure were observed. These findings support the view that enhanced activity of the parathyroid gland may play a part in the early stage of primary hypertension.
Adolescent↗
The effect of vitamin D supplementation on vitamin D status and parathyroid function in elderly subjects.
Vitamin D deficiency is common in the elderly and may lead to secondary hyperparathyroidism, cortical bone loss, and hip fractures. The effect of vitamin D supplementation for 1 yr was studied in 72 people living in a nursing home and 70 people living in an aged people's home. The subjects were randomized into 3 groups: control, and 400 or 800 IU vitamin D3/day. The initial vitamin D status of each subject was classified as deficient or borderline [serum 25-hydroxyvitamin D (25OHD) less than 30 nmol/L] in 79% and adequate (serum 25OHD greater than or equal to 30 nmol/L) in 21%. Serum 25OHD concentrations increased about 3-fold in both groups receiving vitamin D supplementation. Serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] concentrations increased slightly but significantly, and the increase was inversely related to the initial serum 25OHD concentration. Serum intact PTH-(1-84) concentrations decreased about 15% during supplementation in both nursing home and aged people's home residents, whereas serum osteocalcin significantly decreased in the nursing home residents only. We conclude that a vitamin D3 supplement of 400 IU/day adequately improves vitamin D status in elderly people and increases 1,25-(OH)2D concentrations in those with vitamin D deficiency. Supplementation decreases parathyroid function and may depress bone turnover to some degree.
Aged↗
Abnormal responsiveness of nephrogenous cyclic AMP excretion following intravenously administered calcium in normocalcaemic squamous cell cancer patients.
The renal response to calcium infusion was compared in ten normocalcaemic patients with squamous cell cancer and in ten normocalcaemic patients with adenocarcinoma. Both groups were comparable with regard to tumour load, renal function, magnesium and 25-hydroxyvitamin D levels. After injection of 3 mg elementary Ca/kg BW nephrogenous cAMP excretion fell significantly in the group of adenocarcinoma patients (1.74 +/- 1.14 nmol/dl GF vs. 2.81 +/- 1.39 nmol/dl GF; P less than 0.01) and TmPO4/GFR rose significantly at 60 and 120 min. No fall in NcAMP excretion was observed in the group of squamous cell cancer patients (2.18 +/- 0.84 vs. 2.24 +/- 0.84 nmol/dl GF; NS) and TmPO4/GFR remained unchanged. Three of ten patients with squamous cell cancer showed a paradoxical rise in NcAMP excretion following calcium administration. The other seven patients with squamous cell cancer showed a decline in NcAMP excretion (delta NcAMP) which was significantly less than in the ten patients with adenocarcinoma (0.52 +/- 0.16 vs. 1.23 +/- 0.74 nmol/dl GF; P less than 0.05). Increased phosphaturia was observed in three of ten patients with squamous cell cancer after calcium was administered. This also occurred in the presence as well as in the absence of a paradoxical activation of the adenylate cyclase system. It is concluded that the abnormal NcAMP response to calcium-infusion in normocalcaemic squamous cell cancer patients might be due to the presence of a non-suppressible PTH-like substance in these patients.
Adenocarcinoma↗
Increased plasma calcitonin levels in young spontaneously hypertensive rats: role in disturbed phosphate homeostasis.
In young spontaneously hypertensive rats (SHR) and in normotensive Wistar-Kyoto controls (WKY) several parameters of phosphate and calcium homeostasis were determined. At 6 and 8 weeks, blood analysis revealed a significant hypophosphatemia (p less than 0.001) in SHR and twice as high plasma calcitonin levels in SHR than in WKY controls. At 8 weeks, 1,25-dihydroxycholecalciferol concentration was 20% higher in SHR (p less than 0.02) while 25-hydroxycholecalciferol was unaltered (p greater than 0.51). In addition total immunoreactive PTH, iPTH, was slightly increased (p less than 0.07) but intact PTH (1-84) (p greater than 0.90) was not significantly different from age matched WKY controls. Also at 8 weeks, a slightly reduced serum ionized Ca2+ concentration (p less than 0.001) with no change in total serum calcium was found in SHR (p greater than 0.39). Balance studies at 6 and 8 weeks of age revealed no significantly different balances for phosphate (F = 2.5, p greater than 0.10) and for calcium (F = 2.6, p greater than 0.09), although a tendency for slightly more positive balances existed in SHR when compared to WKY. However, SHR excreted significantly less phosphate in the urine than WKY control (F = 0.2, p less than 0.0009). Bone analysis was performed on femora of SHR and WKY of 6 weeks of age. Femora were significantly shorter in SHR (20.54 +/- 0.35 vs. 21.50 +/- 0.05 mm in WKY), whereas bone dry weight (127 +/- 6 vs. 107 +/- 2 mg).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗