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Biomedical subjects

R Bouillon

Publications and source records attributed to R Bouillon.

At least 325 records · Page 18Linked to original sources
PubMed1985

Crystallization and preliminary X-ray analysis of the vitamin D-binding protein from human serum.

The vitamin D-binding protein from human serum has been crystallized from polyethylene glycol as a complex with 25-hydroxyvitamin D3 and examined by X-ray diffraction photography. The space group of the crystals is C2 with a = 203.0 A, b = 75.8 A, c = 90.9 A and beta = 109.5 degrees. There are two molecules of 56,000 dalton in the asymmetric unit. The crystals diffract to about 3.0 A resolution but the patterns exhibit a substantial level of diffuse scatter.

Crystallization↗
PubMed1985

The effect of trauma on serum concentrations of vitamin D metabolites in patients with hip fracture.

In a previous study we observed lower serum concentrations of 25(OH)D, 24,25(OH)2D, and 1,25(OH)2D in patients with hip fracture than in aged control subjects. In order to evaluate the effect of trauma on vitamin D metabolite levels, we measured serum concentrations of vitamin D binding protein (DBP) in 118 patients with hip fracture and 71 aged control subjects. Serum DBP was lower in the patients than in the controls (mean +/- SD 315 +/- 60 vs 371 +/- 44 mg/l, P less than 0.001). Serum DBP correlated positively with serum total protein, albumin, alpha 2-globulin, and the vitamin D metabolite levels in the patients. When correcting for differences in serum DBP, serum 25(OH)D and 24,25(OH)2D still were significantly lower in patients than in controls, whereas serum 1,25(OH)2D was not. The free 1,25(OH)2D index (10(5) x molar ratio 1,25(OH)2D/DBP) was lower in patients than in controls, but the level of significance was marginal. This difference was not significant when patients and controls with impairment of renal function were excluded. It is concluded that the difference in serum 25(OH)D and 24,25(OH)2D between patients and controls is largely preexistent. However, the lower serum 1,25(OH)2D in the patients is mainly caused by the trauma. The free 1,25(OH)2D concentrations are almost similar in the two groups when renal function is normal.

25-Hydroxyvitamin D 2↗
PubMed1985

Monoclonal antibodies to human vitamin D-binding protein.

Monoclonal antibodies to vitamin D-binding protein isolated from human serum have been produced. The antibodies obtained have been shown to be specific for human vitamin D-binding protein by three independent assays. The antibodies recognize human vitamin D-binding protein specifically in an enzyme-linked immunosorbent assay. Human vitamin D-binding protein is detected specifically in both pure and crude samples by a radiometric immunosorbent assay (RISA) and by an immunoprecipitation assay. The anti-human vitamin D-binding protein antibodies cross-react with monkey and pig vitamin D-binding protein, but not with vitamin D-binding protein from rat, mouse, or chicken, as determined by the RISA and immunoprecipitation assays.

Animals↗
PubMed1985

Magnesium administration reverses the hypocalcaemia secondary to hypomagnesaemia despite low circulating levels of 25-hydroxyvitamin D and 1,25-dihydroxy vitamin D.

The effect of parenteral administration of magnesium was studied in five patients with hypomagnesaemic hypocalcaemia. The initial metabolic state was characterized by a normal level of serum immunoreactive parathyroid hormone (iPTH), and by low or undetectable serum 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D (1,25 (OH)2D). A parathyroid response was elicited by the acute intravenous injection of magnesium chloride. In contrast, 1,25(OH)2D did not change up to 24 h after the injection. Intramuscular magnesium sulphate restored serum magnesium and calcium to normal, whereas iPTH was transiently increased. 25OHD remained low and unchanged. 1,25(OH)2D rose very slowly, but the correction of hypocalcemia began before any change in 1,25(OH)2D levels could be demonstrated. Thus, the early correction of hypocalcemia mainly depended on the restoration of an adequate parathyroid function independently of the secretion of 1,25(OH)2D.

25-Hydroxyvitamin D 2↗
PubMed1985

Coexistence of hypocalciuric hypercalcaemia and interstitial lung disease in a family: a cross-sectional study.

In a prospective investigation, a large kindred (twenty-one subjects) with unexplained association of familial hypocalciuric hypercalcaemia and idiopathic interstitial lung disease was studied. Serum calcium was increased in fifteen patients (the youngest being 7 years old) and was associated with hypo- or normocalciuria. The abnormalities were not age-dependent. The serum concentrations of parathyroid hormone, 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3 and calcitonin were normal. In twelve patients the diffusing capacity (DLCO) and/or DLCO per unit lung volume was less than 75% predicted. This was often accompanied by a vital capacity of less than 80% predicted, and increased Tiffeneau index, and a reticulo-micronodular pattern with high diaphragm on chest X-ray. The decrease in DLCO was more pronounced in older non-smoking as well as smoking subjects (P less than 0.02) suggesting a progressing interstitial disease with age. The fibrosing alveolitis, which had been confirmed by open lung biopsy in three subjects, could not be attributed to sarcoidosis, collagen-vascular disease, or exogenous causes. The disturbances in the calcium homeostasis and in the diffusing capacity of the lung coexisted in seven of the twenty-one patients. Apparently, both abnormalities were inherited following an autosomal-dominant pattern but with a different penetration in each person, and seemed not be causally related to each other.

Adolescent↗
PubMed1985

Binding protein for vitamin D and its metabolites in rat mesenteric lymph.

A protein with high affinity for vitamin D3 and 25-hydroxyvitamin D3 in rat mesenteric lymph has been studied. Mesenteric lymph was collected after duodenal instillation of radiolabeled vitamin D3 and 25-hydroxyvitamin D3. As previously described, approximately 10% of vitamin D3 (S. Dueland, J.I. Pedersen, P. Helgerud, and C.A. Drevon, J. Biol. Chem. 257: 146-150, 1982) and 95% of 25-hydroxyvitamin D3 (S. Dueland, J.I. Pedersen, P. Helgerud, and C.A. Drevon, Am. J. Physiol. 245 (Endocrinol. Metab. 8): E463-E467, 1983) recovered in mesenteric lymph were associated with the alpha-globulin fractions. The radioactive vitamin D3 recovered in the lymph fraction with d greater than 1.006 (free of chylomicrons) coeluted with purified rat serum binding protein for vitamin D and its metabolites (DBP) from an antirat DBP column. The results obtained by immunoblotting after sodium dodecyl sulfate polyacrylamide gel electrophoresis showed that this protein in mesenteric lymph had molecular weight and immunological properties identical with purified serum DBP. Purified serum DBP labeled with 125I was injected intravenously and mesenteric lymph was collected. in lymph, suggesting that DBP may be transferred from blood to mesenteric lymph and that plasma and lymph DBP may have a similar origin.

Animals↗
PubMed1985

The nature of opioid involvement in the hemodynamic respiratory and humoral responses to exercise.

After 30 min rest in the lying position, 12 healthy male volunteers (average age 22 years) received, in a randomized double-blind cross-over protocol, either saline or naloxone (10 mg iv followed by a continuous infusion of 10 mg/hr). Thereafter they rested for a further 30 min in the recumbent position and for 15 min sitting on a bicycle ergometer; they then exercised to exhaustion. At rest plasma levels of adrenocorticotropin (ACTH), cortisol, and aldosterone increased during infusion of naloxone, while body temperature decreased. During exercise the difference in plasma ACTH between naloxone and saline periods was abolished, while the differences in plasma cortisol and aldosterone lost statistical significance. Intra-arterial pressure, heart rate, ventilation, O2 uptake, and CO2 output were continuously monitored throughout the experiment and were not affected by naloxone. This was also the case for several hormonal and biochemical measurements, including those of plasma renin, angiotensin II, norepinephrine, 13,14-dihydro-15-keto-prostaglandin F2 alpha, glucose and lactate, and serum insulin and growth hormone. Exercise performance was not changed by naloxone. In conclusion (1) during exhaustive graded exercise of short duration opioidergic inhibition of the pituitary-adrenocortical axis is probably not sustained, (2) apart from the latter mechanism, the present study does not support the hypothesis that endogenous opioids are involved in various hemodynamic, respiratory, and hormonal responses to this type of exercise.

Adult↗
PubMed1985

The inherited association of interstitial lung disease, hypocalciuric hypercalcemia, and defective granulocyte function.

The history and pulmonary histopathology of 3 siblings, presenting with the association of idiopathic interstitial lung disease, hypocalciuric hypercalcemia, and an intrinsic defect in granulocyte function are described. Prospective examination of 40 family members indicated that the 3 abnormalities are inherited according to an autosomal dominant pattern with, however, a variable penetration. Lung biopsies in the index cases revealed an interstitial infiltration of inflammatory cells and aggregates of conchoid bodies surrounded by multinucleated giant cells. Bronchoalveolar lavage was performed in 11 subjects and often showed an elevated cell recovery and abnormal cell distribution indicative of active alveolitis. In several subjects, multinucleated giant cells were found. The diffusing capacity (in percent predicted) showed a significant decrease with age, independent of smoking habits. The hypocalciuric hypercalcemia was unaffected by steroids or parathyroidectomy. It was not associated with abnormal levels of parathyroid hormone, calcitonin, 25-hydroxy-vitamin D3, 1,25-dihydroxy-vitamin D3, or angiotensin-converting enzyme.

Adult↗
PubMed1985

1,25-Dihydroxyvitamin D and vitamin D-binding protein are both decreased in streptozotocin-diabetic rats.

Calcium and vitamin D metabolism were studied in streptozotocin-treated rats up to 10 days after the induction of diabetes. Proteinuria, hypercalciuria, and hyperphosphaturia appeared as early as 3 days after diabetes induction and were reversed by insulin. The serum proteins and fasting calcium concentrations were decreased in untreated diabetic rats. The concentration of serum vitamin D binding protein (DBP) was higher in male than in female control rats (mean +/- SD; 555 +/- 73 vs. 348 +/- 28 mg/liter, P less than 0.001). When sequentially measured in male untreated diabetic rats, DBP concentration steadily decreased. Compared with control values, DBP was reduced 19%, 28%, and 32% on days 3, 6, and 10, respectively, after induction of diabetes in male rats. In female animals, DBP was reduced 22% on day 10 of diabetes. DBP concentration was corrected by insulin treatment of diabetic rats and remained normal in streptozotocin-treated animals that did not develop diabetes. The serum concentration of 25-hydroxyvitamin D3 was similar in both sexes and was not affected by diabetes. Like DBP, the concentration of total 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] was higher in male than in female control rats (120 +/- 24 vs. 96 +/- 17 ng/liter, P less than 0.001), but 10 days after induction of diabetes this concentration decreased by 37% and 29% in male and female rats, respectively. The free 1,25-(OH)2D3 concentration, estimated from the molar 1,25-(OH)2D3/DBP ratio, was similar in both sexes and was not decreased by diabetes. We conclude that experimental diabetes in the rat induces a decrease in DBP concentration and a concomitant decrease in total but not in free 1,25-(OH)2D3 concentrations. This may indicate that diabetes decreases circulating 1,25-(OH)2D3 concentrations through alterations in DBP levels.

Animals↗
PubMed1985

Presence of immunoreactive vitamin D-binding protein in rat yolk sac endodermal cells.

The visceral yolk sac is, in the rat, an organ which possesses true placental functions. We recently showed that yolk sac is involved in the control of metabolism and action of vitamin D in the fetoplacental unit, since its endodermal cells contain a 24-hydroxylase for vitamin D metabolites and the 1,25-dihydroxyvitamin D receptor. In the present work, by using indirect immunoperoxidase staining, we demonstrate that an immunoreactive vitamin D-binding protein (DBP) is present in this yolk sac throughout embryonic and fetal development. It is mainly located at the apex of the endodermal cells. Immunoprecipitation studies of radioactive proteins synthesized in vitro by yolk sac explants showed that yolk sac DBP, in contrast to alpha-fetoprotein, is not synthesized in situ by yolk sac. This result, combined with the location of DBP at the apex of the endodermal cells which face the uterus, strongly suggests that yolk sac DBP is of maternal origin. The concomitant presence in the endodermal cells of this DBP, of the 1,25-dihydroxyvitamin D receptor, and of the system hydroxylating vitamin D metabolites in position 24, certainly has considerable physiological significance.

Animals↗
PubMed1985

Differential responses of plasma aldosterone, cortisol and adrenocorticotropin to two dopamine receptor antagonists.

The response of plasma aldosterone, cortisol and adrenocorticotropin (ACTH) to the dopamine antagonists metoclopramide and domperidone, administered intravenously in a dose of 1 mg/kg, was investigated in healthy volunteers. Within 15 min after metoclopramide administration, plasma aldosterone (+ 99%), cortisol (+ 75%) and ACTH (+ 55%) increased (p less than 0.001), whereas the plasma levels of these hormones were not altered after domperidone. The differential responses of plasma aldosterone and cortisol to high doses of metoclopramide and domperidone are therefore, at least partially, mediated via the enhanced adrenal stimulation by ACTH after metoclopramide.

Adrenocorticotropic Hormone↗
PubMed1985

Resorptive versus absorptive hypercalciuria in sarcoidosis: correlations with 25-hydroxy vitamin D3 and 1,25-dihydroxy vitamin D3 and parameters of disease activity.

Sarcoidosis is frequently attended by hypercalciuria and sometimes by hypercalcaemia. The type of hypercalciuria and its relationships with disease extension and activity have rarely been investigated. In order to clarify these issues we undertook an investigation by a calcium absorption test in 39 patients with untreated thoracic sarcoidosis, and tried to establish correlations with vitamin D3 metabolism and some features of the disease. We found three types of responses. Group I (n = 12) with a normal test had normal 1,25-(OH)2D3 and rare extrathoracic localisations. Group II (n = 14) with absorptive hypercalciuria had higher serum calcium; 1,25-(OH)2D3 (p less than 0.001) and the free 1,25-(OH)2D3 index (p less than 0.05) were raised. Sarcoidosis was more often inflammatory, developing and disseminated. Group III (n = 13) had resorptive hypercalciuria, and hypercalcaemia was frequent. 1,25-(OH)2D3 (p less than 0.01) and the free 1,25-(OH)2D3 index (p less than 0.05) were raised but to the same degree as in Group II. Sarcoidosis was more disseminated and developing than in Groups I and II. In the 39 patients, iPTH and nephrogenous cAMP were low. Post-calcium load urinary calcium/creatinine (Ca/Cr) and 1,25-(OH)2D3 were correlated (p less than 0.05). Extrathoracic extension was associated with higher fasting urinary Ca/Cr (p less than 0.001), and development with higher post-load urinary Ca/Cr (p less than 0.001). Thus, absorptive hypercalciuria is related to the development of sarcoidosis and can be explained by high free 1,25-(OH)2D3, while resorptive hypercalciuria seems to be linked with disease extension. In such a case, the mechanism of osteolysis is not solely accounted for by high 1,25(OH)2 vitamin D3 serum levels, and we postulate that some other factor is at work, related to the extent of the granulomatous process.

Absorption↗
PubMed1984

Influence of vitamin D status on insulin secretion and glucose tolerance in the rabbit.

The influence of vitamin D status on insulin secretion and glucose tolerance was studied by a longitudinal design in the rabbit. Intravenous glucose tolerance tests were performed in Dutch rabbits (n = 12) before and after nutritional vitamin D deficiency, characterized by an absence of circulating 25-hydroxyvitamin D3, a 50% decrease in 1,25-dihydroxyvitamin D3, and a 16% decrease in serum calcium concentrations. Glucose-induced insulin secretion was reduced by 41% as early as 2 months after the start of the vitamin D-deficient diet and was associated with an impairment of glucose tolerance. An iv calcium infusion restored the serum calcium concentration of the vitamin D-deficient rabbits (n = 5), but did not improve glucose-mediated insulin secretion. When these animals received a single ip injection of 100 ng 1,25-dihydroxyvitamin D3 10 h before the glucose test, their insulin responses significantly increased. Supplementation with 25-hydroxyvitamin D3 for 2 weeks in another group of rabbits (n = 4) resulted in marked improvement in glucose-stimulated insulin release and glucose tolerance. These results show that vitamin D affects glucose-induced insulin secretion by a mechanism that involves more than its regulating action on serum calcium concentration.

Animals↗
PubMed1984

Serum vitamin D metabolites and their binding protein in patients with liver cirrhosis.

Serum parameters of calcium metabolism were measured in 32 consecutive patients with biopsy-proven cirrhosis due to either hepatitis (n = 13), alcohol abuse (n = 11), Wilson's disease (n = 3), or primary or secondary biliary cirrhosis (n = 5). All measurements were normal in the small group of patients with Wilson's disease. The serum concentrations of albumin, vitamin D-binding protein, total calcium, phosphorus, and 1,25-dihydroxyvitamin D3 (1,25-(OH2)D3) were decreased in the other patients with cirrhosis, but their mean serum concentrations of ionized calcium, 25-hydroxyvitamin D3 (25-OHD3) and free 1,25-(OH2)D3 index were normal. A slight but significant increase in the serum PTH measured using a carboxyl-terminal antiserum was found. A significant correlation was found between the serum concentration of either albumin or vitamin D-binding protein and the serum concentrations of total calcium, 25-OHD3, 1,25-(OH2)D3, and PTH but not with ionized calcium or free 1,25-(OH2)D3 index. The observed abnormalities of calcium metabolism in unselected patients with cirrhosis were mainly due to decreased protein synthesis. Only the patients with severe cirrhosis had decreased concentrations of 25-OHD3 but they were nevertheless able to maintain a normal ionized serum calcium and free 1,25-(OH2)D3 level, possibly by means of compensatory hyperparathyroidism.

Adolescent↗
PubMed1984

Altered parathyroid set point to calcium in familial hypocalciuric hypercalcaemia.

Changes in calcium concentration were induced by an infusion of disodium-EDTA or calcium in 2 members of a family suffering from hypocalciuric hypercalcaemia ( FHH ) associated with interstitial lung disease. These changes in calcium demonstrated an inverse linear relationship with the changes in serum parathyroid hormone (PTH). Infusion of EDTA in control subjects and in patients with an adenoma or hyperplasia of the parathyroid glands also showed inverse relationships between calcium and PTH. The correlation between serum calcium and serum PTH was significant over the range observed during the induced hypo- and/or hypercalcaemia in controls and in patients with FHH or adenoma. The regressions were, however, shifted relative to each other: in comparison with controls, the FHH was displaced upwards and to the right, although not as far as the adenomas. These findings suggest the existence of an elevated set point for extracellular calcium (or calciostat ) in FHH .

Adenoma↗