Translocation of c-myc into the immunoglobulin heavy-chain locus in human acute B-cell leukemia. A molecular analysis.

We report the molecular analysis of primary cells from four cases of human B-cell malignancies each with an 8;14 chromosomal translocation involving the c-myc proto-oncogene and the immunoglobulin (Ig) gene cluster. In two cases of B-cell acute lymphocytic leukemia (B-ALL) the c-myc is truncated, rearranged into the Ig C alpha 1 locus and over-expressed in two abnormal mRNAs of approximately 2.0 and 2.

Raised levels of calcium-binding protein in plasma following insulin-induced hypoglycaemia in the pig.

Insulin-induced hypoglycaemia in the pig elicited sharp increases in the plasma concentrations of vitamin D-dependent calcium-binding protein (CaBP) and cortisol and a decrease in plasma inorganic phosphate. Glucose infusion following insulin administration abolished the increases in plasma CaBP and cortisol in response to insulin and reduced the hypophosphataemia. The percentage increases in plasma CaBP and cortisol in response to insulin-induced hypoglycaemia were reduced when the pigs were fed a low-calcium diet, but the hypophosphataemic response was similar.

Parathyroid glands, calcium, and vitamin D in experimental fluorosis in pigs.

The purpose of this study was to determine whether total serum calcium, parathyroid gland structure, and/or levels of parathyroid hormone, 1,25 and 24,25 DHCC, are altered in pigs with dental and skeletal fluorosis. Eight experimental animals receiving 2 mg F-/kg b.w.

The effects of betamethasone on plasma and intestinal calcium binding protein and on 25-hydroxyvitamin D3 metabolism in the pig.

Betamethasone (50 micrograms/kg body weight/day) given to young pigs reduced calcium absorption, growth and plasma vitamin D dependent calcium binding protein (CaBP) concentration. No changes occurred in plasma 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and intestinal CaBP concentrations. 1,25(OH)2D3 (0.

Effects of acute and chronic treatment with glucocorticoids on the intestinal absorption of calcium and phosphate and on plasma 1,25-dihydroxyvitamin D levels in pigs.

We have used young pigs, each prepared surgically with a Thiry-Vella loop of proximal small intestine, to study the time course of changes in the intestinal absorption of calcium, phosphate, sodium, glucose and water and on the plasma levels of 1,25-dihydroxyvitamin D after treatment of the animals with glucocorticoids. Perfusion of the intestinal loop for 6 h with a solution containing hydrocortisone or beta-methasone was without effect on the absorption of calcium or phosphate. The oral administration of betamethasone stimulated the absorption of calcium and phosphate by 15-20% for 2-3 days before the trend was reversed and absorption was progressively reduced.

Effect of 1,25-dihydroxyvitamin D deficiency on the metabolic clearance rate of 1,25-dihydroxyvitamin D3: studies using pigs with vitamin D-dependent rickets type 1.

We have used pigs with inherited vitamin D-dependent rickets type 1 to study the effect of 1,25-dihydroxyvitamin D deficiency on the metabolic clearance rate of 3H-1,25-dihydroxyvitamin D3 infused to steady-state levels in plasma. Plasma levels of 1,25-dihydroxyvitamin D were 24 +/- 1 (SEM) pmol/l in the hypocalcaemic, homozygous piglets and 196 +/- 27 pmol/l in their normocalcaemic, heterozygous siblings. The metabolic clearance rate of 1,25-dihydroxyvitamin D3 was the same in both normal heterozygous (0.

Vitamin D-dependent rickets type I in pigs.

We have bred a strain of pigs with an inherited condition of hypocalcaemic rickets, transmitted by an autosomal-recessive mechanism. Homozygous (affected) piglets grew at half the rate of their heterozygous (clinically normal) littermates, and developed profound hypocalcaemia with severe secondary hyperparathyroidism and hypophosphataemia by 8 weeks of age. In the hypocalcaemic piglets, plasma 1,25-dihydroxyvitamin D levels were low or undetectable, and 24,25-dihydroxyvitamin D3 levels were also reduced despite 25-hydroxyvitamin D3 levels being 2-fold higher.

Effect of dietary calcium and phosphorus depletion on vitamin D metabolism and calcium binding protein in the growing pig.

Twenty-four young pigs were divided into three groups and each fed a replete, low calcium (Ca) or low phosphorus (P) diet. It was found that the deficient diets induced rises in renal 25 hydroxy-vitamin D 1,hydroxylase (1-hydroxylase) activity, circulating 1,25 dihydroxy-vitamin D3 (1,25 (OH)2-D3) and Ca binding protein (CaBP) and intestinal 1,25(OH)2D3 and CaBP. All these rises were statistically significant in the low Ca group but only the rises in the 1-hydroxylase activity and intestinal 1,25(OH)2D3 were significant in the low P group.

Haemoglobin switching in human embryos: asynchrony of zeta----alpha and epsilon----gamma-globin switches in primitive and definite erythropoietic lineage.

Haemoglobin switching in humans provides a unique model for investigating the mechanisms underlying expression of a developmentally regulated gene family. Numerous studies have focused on the switch from fetal to adult (that is, gamma----beta) globin, but little is known about the embryonic----fetal (that is, zeta----alpha and epsilon----gamma) switches, as well as the transition from 'primitive' yolk sac to 'definitive' liver erythropoiesis. Here we have studied the embryonic----fetal haemoglobin switches in yolk sac, liver and circulating blood erythroblasts from 25 embryos and 6 fetuses.

Translocation and rearrangement of c-myc into immunoglobulin alpha heavy chain locus in primary cells from acute lymphocytic leukemia.

We report the molecular analysis of an 8;14 reciprocal chromosome translocation in a case of acute lymphocytic leukemia (L3 type). DNA from primary leukemic cells was analyzed on the basis of restriction endonuclease mapping by hybridization with various human c-myc and Ig heavy chain probes. The breakpoint of the translocation is within an approximately equal to 200-base-pair region in the first intron of the c-myc gene.

Association of heterocellular HPFH, beta(+)-thalassaemia, and delta beta(0)-thalassaemia: haematological and molecular aspects.

An Italian family in which heterocellular hereditary persistence of fetal haemoglobin (HPFH) interacts with both beta(+)- and delta beta-thalassaemia is described. The index case was an 8 year old girl who was presumed to inherit both heterocellular HPFH and beta (+)-thalassaemia from her mother and delta beta-thalassaemia from her father. She was healthy and never needed blood transfusions.

Magnesium absorption from the digestive tract of sheep.

Factors affecting absorption of Mg from the ovine rumen have been studied using either a pouch constructed from part of the dorsal rumen or by an isolated washed rumen technique in vivo. Net absorption of Mg against the prevailing electrochemical gradient was observed. An increase in the K/Na ratio within the rumen led to an increase in the potential difference across the rumen wall, blood positive, and to a decrease in the net efflux of Mg from the rumen.

Delta beta-thalassaemia in southern Italy: evidence for a single mutational event.

Haematological and molecular studies on 32 heterozygotes for G gamma A gamma delta beta(0)-thalassaemia from 15 unrelated families from southern Italy are reported. The haematological features of G gamma A gamma delta beta(0)-thalassaemia carriers are compared with those of beta-thalassaemia and Hb Lepore heterozygotes. Striking similarity exists between the phenotypic expression of beta-thalassaemia and Lepore mutations.

Hemopoietic development in human embryos.

We report studies on hemopoietic progenitors and precursors in human embryos and fetuses at 4 to 5 through to 9 to 10 weeks from conception, as well as the corresponding in vivo Hb synthesis pattern. Particular attention is paid to the morphology of 5- to 8-week liver cells, as evaluated by both conventional and electron microscopy. On the basis of these observations, a unifying monoclonal model is proposed for human embryonic hemopoiesis.

Molecular heterogeneity of beta thalassaemia in the Italian population.

Fifty-one subjects originating from Southern Italy and affected by Cooley's anaemia have been studied in order to define the degree of heterogeneity of beta thalassaemia mutations in this high incidence area. Restriction endonuclease mapping has been carried out on genomic DNA by the Southern blot technique both to exclude the existence of gross deletions or rearrangements and to establish the relative frequency of four polymorphic restriction sites (i.e.

Heterocellular hereditary persistence of fetal hemoglobin (HPFH). Molecular mechanisms of abnormal gamma-gene expression in association with beta thalassemia and linkage relationship with the beta-globin gene cluster.

We report a study of four families of Italian origin in which heterocellular HPFH is inherited linked to beta thalassemia over two or three generations. The HPFH + beta thalassemia carriers showed thalassemic blood pictures and elevated HbF and F-cell number without increase in the HbF/F-cell content. Association of this gene complex with a second beta thalassemia trait gives rise to a mild clinical picture characterized by 9-12 g/dl of mainly HbF in peripheral blood and no transfusion requirement.

The effects of betamethasone, low calcium and low phosphorus diets on growth in chicks.

The effects of oral betamethasone (25 micrograms/kg/d), low calcium (1 g/kg), and low phosphorus (2,5 g/kg) diets on weight gain were investigated in 513 growing chicks. The chicks were divided according to initial weight into a lower weight group (less than 100 g each) and a higher group (more than 100 g each). The increases in weight were recorded after periods of 7, 14 and 21 days.

Molecular mechanisms of human hemoglobin switching: selective undermethylation and expression of globin genes in embryonic, fetal, and adult erythroblasts.

The globin chain synthetic pattern and the extent of DNA methylation within embryonic, fetal, and adult beta-like globin gene domains were evaluated in greater than or equal to 90% purified human erythroblasts from yolk sacs and fetal livers in the 6- to 12-wk gestational period as well as from adult marrows. The 6-wk erythroblasts produce essentially embryonic epsilon chains, whereas the 12-wk erythroblasts synthesize largely fetal gamma globin and the adult marrow erythroblasts synthesize almost exclusively adult beta chains. In all phases of ontogenic development, a strong correlation exists between DNA hypomethylation in the close flanking sequences of globin genes and their expression.

The transfer of calcium during perfusion of the placenta and intact and thyroparathyroidectomized sheep.

Placental perfusions were carried out in six ewes during the last two weeks of gestation. Perfusions were carried out using autologous fetal blood and the flow rates adjusted to give a perfusion pressure of 50--70 mmHg. Perfusion plasma calcium concentrations rose steadily throughout the perfusions achieving a mean increase of 1.

The delta beta crossover region in Lepore boston hemoglobinopathy is restricted to a 59 base pairs region around the 5' splice junction of the large globin gene intervening sequence.

Genomic DNA from a hemoglobin (Hb) Lepore Boston (delta 87 Gln beta 116 His) homozygote of Southern Italian origin has been studied in order to map the fusion point between the delta and beta genes. An Ava II restriction endonuclease recognition sequence, located 12 base pairs (bp) downstream from the 5' end of the beta gene large intervening sequence, has been taken as marker of the beta-like portion of the fusion gene. This site was present even in the delta beta gene, allowing the localization of the crossover area to a 59-bp region extending from the first nucleotide of the Leu codon in position 88 to the 11th nucleotide of the large intervening sequence.

The effect of betamethasone on duodenal calcium absorption and 1,25-dihydroxy vitamin D3 production in the chick.

Duodenal absorption of calcium, renal 25-hydroxycholecalciferol-1-hydroxylase activity, percentage bone ash, growth rate and plasma levels of Ca and P were all measured in chicks which had been treated with the synthetic glucocorticoid, betamethasone, at the therapeutic dose level of 25 microgram/kg daily. It was found that treatment for 2-3 weeks resulted in a significant reduction in Ca absorption rate, renal 1-hydroxylase activity and growth rate but an increase in bone ash and plasma Ca. If betamethasone was administered for 10 days and then stopped 4-13 days before these parameters were measured, a compensatory increase was found in 1-hydroxylase activity while the Ca absorption rate attained control values in all but the 4 day group in which it was still significantly depressed.

Calcium homeostasis in the fetal pig.

Acute studies have been carried out with pregnant sows and their fetuses during the last 2 weeks of gestation. In blood samples obtained simultaneously it was shown that the concentrations of ionized calcium, calcitonin and parathyroid hormone (PTH) in fetal plasma were all greater than the corresponding values in maternal plasma. In contrast, the fetal concentrations of 24,25-dihydroxy vitamin D3 were lower than maternal and those of 1,25-dihydroxy vitamin D3 were not significantly different.