Noncollinear magnetic hyperfine fields in the Ag spacers of Fe/Ag multilayers.

Nearly perpendicular magnetic hyperfine fields have been observed for the first time in the Ag "spacers" of Fe/Ag multilayers using low temperature nuclear orientation of (110)Ag(m) at 6 mK. At the same time, vibrating sample magnetometry measurements at temperatures down to 4 K have shown the magnetic anisotropy of the Fe to be in plane. The direction of the Ag hyperfine field is thus noncollinear (nearly orthogonal) to the Fe anisotropy. These results are compared with full potential linearized augmented plane wave calculations using the wien97 code.

More familial leukaemia in ALL patients with both unexplained high transcortin levels and an HLA antigen Cw3.

In a group of 74 adult ALL patients 25 had a transcortin level greater than or equal to 3 SD above the normal mean, 15 expressed an HLA-Cw3 antigen and 11 combined both characteristics. In this subgroup of 11 ALL patients, five had familial leukaemia, i.e. at least one relative with acute leukaemia or lymphoma. On the other hand, only three examples of familial leukaemia were found in a series of 59 ALL patients with one or none of these two characteristics (relative risk: 15.6; P less than 0.001).

Evidence for an interaction of insulin and sex steroids in the regulation of vitamin D metabolism in the rat.

Vitamin D metabolites and vitamin D-binding protein (DBP) were measured in non-diabetic rats and in rats made diabetic with streptozotocin. The animals were studied in the intact state, after gonadectomy and during pregnancy. In male non-diabetic rats the serum concentrations of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) and DBP decreased after orchidectomy and were restored by treatment with testosterone. In female non-diabetic rats, these parameters increased after ovariectomy. Increased 1,25-(OH)2D3 and decreased DBP concentrations were found during pregnancy in non-diabetic rats. After the induction of diabetes in intact rats of both sexes, the concentration of DBP decreased, but a significant decrease in the concentration of 1,25-(OH)2D3 was found in male animals only. After ovariectomy, however, 1,25-(OH)2D3 decreased also in female diabetic rats. Both orchidectomy and insulin deficiency depressed serum concentrations of 1,25-(OH)2D3 (-22 and -45% respectively) and DBP (-14 and -29% respectively), but the effects of insulin deficiency were greater than those of androgen withdrawal. Moreover, the testosterone concentration was twofold lower in intact male diabetic rats than in non-diabetic animals. Insulin, but not testosterone treatment, however, restored DBP and 1,25-(OH)2D3 concentrations in diabetic rats, and insulin was effective in intact as well as in gonadectomized animals. This study shows that insulin deficiency decreases the concentrations of DBP and 1,25-(OH)2D3 in the rat, and that these decreases are facilitated by androgens, but counteracted by oestrogens.

HLA antigen CW3 combined with unexplained high transcortin levels is found in patients with acute lymphoblastic leukemia but not in their parents, sibs and offspring.

ALL patients with an unexplained high transcortin level (greater than or equal to 3 SD above the normal mean) have a higher incidence of HLA antigen Cw3 than patients with a lower transcortin level. Although both factors are inheritable, their combination occurs only rarely in the family members of these patients.

Phylogenetic study of transcortin using monoclonal antibodies.

We produced monoclonal antibodies that recognise three distinct epitopes of human transcortin. These epitopes are present on transcortin of humans with normal and altered transcortin levels, as well as on a variant with lower affinity for cortisol. One epitope is present on transcortin of Old World Monkeys and apes, the others are only present on transcortin of apes. The epitopes are not present on transcortin of other species. These results indicate that human transcortin contains a highly evolved and a more conserved part.

Vitamin D metabolites and their binding protein in adult diabetic patients.

Vitamin D metabolites and vitamin D-binding protein were measured in the serum of nonketotic Bantu and Caucasian insulin-requiring diabetic subjects from Zaire and Belgium, respectively. In Caucasian diabetics, whether untreated (N = 18) or insulin treated (N = 26), no abnormalities were found. The Bantu diabetics (N = 20) were more insulin-deficient and had a poorer glucose control than the Caucasians. They presented, compared with Bantu controls, a significant decrease in the serum concentrations of 25-hydroxyvitamin D3 (26 +/- 10 vs. 35 +/- 14 micrograms/L, P less than .01), 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] (38 +/- 15 vs. 58 +/- 17 ng/L, P less than .001), and vitamin D-binding protein (303 +/- 55 vs. 356 +/- 41 mg/L, P less than .001). The decreased concentrations of vitamin D metabolites in the adult Bantu diabetic patients may be partly explained by a concomitant decrease in the concentration of vitamin D-binding protein, possibly due to insulin deficiency. The ratio between the molar concentrations of 1,25-(OH)2D3 and vitamin D-binding protein, used as an index of the free hormonal level, was also decreased, in association with a decreased serum calcium level. In conclusion, no abnormalities in vitamin D metabolism were found in Caucasian insulin-dependent diabetics, whereas low serum 1,25(OH)2D3 concentrations and hypocalcemia were found in poorly controlled Bantu diabetic subjects.

Steroid-carrier proteins in patients with multiple myeloma.

Patients with multiple myeloma have transcortin levels lower than normal. This is due in essence to a subgroup of patients producing IGG heavy chains with lambda light chains. Patients producing IGG with predominantly kappa light chains have almost normal transcortin levels. On the other hand, the binding activity of the steroid binding beta globulin (SB beta G) of the kappa type of multiple myeloma is significantly higher than the steroid binding of the lambda type of multiple myeloma. The serum levels of vitamin D binding protein (DBP) fall in the normal range.

Transcortin and vitamin D-binding protein levels in mouse serum.

The influence of age, sex and strain on the serum concentration of transcortin (corticosteroid-binding globulin) and vitamin D-binding protein (DBP) in mice was investigated. The effect of age was studied in two strains, C57BL/6JPfd and BALB/cmHeAPfd. The concentration of transcortin and DBP increased with age. In young animals the concentration of each protein showed a significant strain difference, which disappeared in older mice for DBP, but not for transcortin. In 7-day-old animals, no sex difference was observed for either protein, but in older animals a clear sex difference was found for transcortin. Adult males tended to have somewhat higher levels of DBP than adult females, but this difference was significant only on day 70. The variation in transcortin and DBP levels was further investigated in a large number of mouse strains. The DBP concentration did not markedly vary among strains (5.98-9.65 mumol/l in males and 5.08-8.85 mumol/l in females). Transcortin, however, showed marked strain variations, ranging from 0.72 to 2.06 mumol/l in males and from 1.02 to 4.55 mumol/l in females and there was a significant correlation (r = 0.66, n = 26, P less than 0.001) between the mean transcortin levels in males and females of different strains. Interstrain variation was much higher than intrastrain variation or variation among related strains, suggesting that the transcortin concentration is largely controlled by genetically determined factors. There was a significant correlation (r = 0.82, n = 9, P less than 0.01) between the mean corticosterone and transcortin concentrations (measured at 21.00 h).(ABSTRACT TRUNCATED AT 250 WORDS)

Decreased free 1,25-dihydroxycholecalciferol index in patients with the nephrotic syndrome.

The serum concentrations of calcium, phosphorus, parathyroid hormone, vitamin D3 metabolites and their transport protein (DBP) were measured in 18 patients with the nephrotic syndrome (mean daily proteinuria 8.8 g). The glomerular filtration rate was normal in 13 patients while the remaining 5 had a mild degree of renal failure. The serum concentrations of total protein, albumin and DBP were significantly decreased in patients with the nephrotic syndrome. The serum calcium concentration was decreased but the calculated ionized calcium concentration remained normal. The serum concentrations of 25-hydroxycholecalciferol (5.3 +/- 3.1 micrograms/l) and 1,25-dihydroxycholecalciferol [1,25-(OH)2D3 (20 +/- 12 ng/l)] were significantly lower in patients with the nephrotic syndrome and normal glomerular filtration rates than in normal controls (14.4 +/- 4 micrograms/l and 42 +/- 13 ng/l, respectively). The free 1,25-(OH)2D3 index was also significantly below normal (0.9 +/- 0.4 vs. 1.8 +/- 0.4). Total and free 1,25-(OH)2D3 were still further reduced in patients with mild renal failure. The nephrotic syndrome thus results in mild vitamin D depletion with decreased free 1,25-(OH)2D3 concentrations but generally without secondary hyperparathyroidism.

Pancreatic secretion in man with subclinical vitamin D deficiency.

The effects of subclinical vitamin D deficiency and vitamin D supplementation on oral glucose tolerance and secretion of pancreatic hormones were studied in 10 diphenylhydantoin-treated epileptic patients and 15 geriatric patients. Their mean serum concentrations of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 decreased markedly, but returned to normal within 2 weeks of oral supplementation with 25-hydroxyvitamin D3. The serum concentration of ionized calcium was within the normal range before treatment, and remained unchanged. Serum parathyroid hormone was increased during vitamin D deficiency, but decreased significantly (p less than 0.05) afterwards. In vitamin D-deficient epileptic and geriatric patients, the 2- and 3-h insulin levels after glucose ingestion were increased when compared with control values, and glucagon secretion was not suppressed by glucose. Oral glucose tolerance of both groups of patients did not change after 25-hydroxyvitamin D3 supplementation. Insulin secretion remained unchanged in geriatric patients, but was reduced to normal values in epileptic patients. Glucagon suppressibility by glucose was partly restored after vitamin D supplementation in epileptic patients but not in geriatric patients. In contrast to that observed in severely vitamin D-deficient rats or rabbits, correction of subclinical vitamin D deficiency failed to enhance insulin secretion or to improve glucose tolerance in man.

Hyperthyroidism influences the distribution and apolipoprotein A composition of the high density lipoproteins in man.

Hyperthyroidism has a different influence on the major high density lipoprotein (HDL) components cholesterol, apoprotein (apo) A-I, and apo A-II. To characterize in greater detail the alterations induced by hyperthyroidism within the HDL subclasses, we investigated HDL distribution and composition in 11 hyperthyroid women before and during treatment. The plasma concentrations of total cholesterol, HDL cholesterol, phospholipids, apo A-I, and apo B were decreased when the patients were hyperthyroid compared with the values during treatment. Apo A-II and apo C-III levels were only slightly lower in the hyperthyroid state. Triglyceride and apo E concentrations did not change significantly during therapy. Analysis of lipoprotein subclasses separated by isopycnic ultracentrifugation revealed 1) marked decreases in low density lipoprotein (LDL) cholesterol, phospholipids, and apo B; 2) less pronounced reductions in the very low density lipoprotein (VLDL) lipid and apo B concentrations; and 3) a consistent decrease in the HDL2b (density, 1.063-1.100 g/ml) fraction in the hyperthyroid patients. The reduction in HDL2b mass was associated with lower concentrations of HDL2b cholesterol, phospholipids, and apo A-I. The HDL2b apo A-II levels remained constant during treatment. Hyperthyroidism, therefore, modified the apo A composition of the HDL2b particles and resulted in a decreased molar apo A-I to apo A-II ratio within HDL2b. Further analysis of HDL particles differing in their apo A composition; i.e. HDL particles containing apo A-I only [(A-I)HDL] or containing both apo A-I and A-II [(A-I + A-II)HDL], by immunological procedures suggested that hyperthyroidism influenced the apo A content of HDL2b mainly by changing the proportions of (A-I)HDL and (A-I + A-II)HDL and the amount of apo A-I associated with (A-I)HDL. Treatment reversed the preferential decrease in (A-I)HDL within the HDL2b subclass. The particle sizes within HDL subfractions, measured by polyacrylamide gradient gel electrophoresis, were similar in the untreated and treated patients. Consequently, the decreased mass of apo A-I and lipids within HDL2b in the hyperthyroid patients could be attributed to a reduced number of identically sized particles within this fraction. These data demonstrate that the thyroid hormones are important regulators of HDL metabolism through their influence on the concentration and distribution of apo A-I.