A new mechanism for induced vitamin D deficiency in calcium deprivation

Synthesis of vitamin D in the skin in response to ultraviolet light is the main determinant of vitamin D status in man and it is therefore surprising that rickets and osteomalacia, clinical signs of vitamin D deficiency, remain common in tropical and subtropical countries. Skin pigmentation can reduce vitamin D formation but this is a negligible limitation in people exposed to abundant ultraviolet light. Earlier studies in animals and man suggested that another environmental factor, the low calcium/high cereal diet typical of susceptible populations, might affect the efficiency of vitamin D utilization. We show here in rats that the rate of inactivation of vitamin D in the liver is increased by calcium deprivation. The effect is mediated by 1,25-dihydroxyvitamin D, produced in response to secondary hyperparathyroidism, which promotes hepatic conversion of vitamin D to polar inactivation products that are excreted in bile. This finding has widespread implications both for understanding the pathogenesis of endemic rickets and in that it provides a unifying mechanism for the development of vitamin D deficiency in many clinical disorders.     

Spatial relationship of the Fis binding sites for Hin recombinational enhancer activity

Site-specific recombination reactions involve the joining or rearrangement of discrete DNA segments in a highly precise manner. A site-specific DNA inversion regulates the expression of flagellin genes in Salmonella by switching the orientation of a promoter. Analysis of the reaction has shown that, in addition to DNA sequences at the two boundaries of the 1-kilobase invertible segment where strand exchange occurs, another cis acting sequence is required for efficient inversion. This 60-base-pair enhancer-like sequence can function at many different locations and in either orientation in a plasmid substrate. It includes two binding sites for a host protein called Factor II or Fis (refs 4 and 5). Here we have investigated the importance of the spatial relationship between the two Fis binding sites for enhancer activity and have found that the correct helical positioning of the binding sites on the DNA is critical. However, this result could not be accounted for by effects on Fis binding. We propose a model for enhancer function in which the enhancer region acts to align the recombination sites into a specific conformation required for productive synapsis.     

Epithelial cell processes in the development of the secondary palate in the mouse

Summary Ultrastructural studies of palatal shelves of Tuck A mice embryos aged 12.25–14.25 days show discontinuities of the epithelial basement membrane traversed by epithelial cell processes before the onset of midline degenerative changes.     

Measurement of urinary steroid production rates using stable-isotopes and GC-MS

Summary The urinary production rate of pregnenolone has been determined for a male subject using 7,7-d₂-pregnenolone as an isotopic tracer.To whom correspondence should be addressed.     

Inactivation of yeast glucose-6-P dehydrogenase by aspirin

Summary Glucose-6-P dehydrogenase is irreversibly inactivated by treatment with Na salts of aspirin. Kinetic data show that 1 molecule of aspirin reacts with each active unit when the enzyme is inactivated. The rate of inactivation is enhanced with increasing pH but is reduced in the presence of glucose-6-P or NADP⁺. Na salicylate fails to inactivate the enzyme.This work was supported by grant RR-8006 from the General Research Branch, Division of Research Resources, NIH (USA).     

Cloning and sequence analysis of the cDNA for the rat atrial natriuretic factor precursor

Atrial extracts contain factors which induce potent natriuresis changes in renal haemodynamics, and relax pre-contracted vascular smooth muscle. Low-molecular-weight peptides which mimic these actions have now been purified by several groups, including ours (see accompanying paper), and higher-molecular-weight proteins with similar but less potent biological activities have also been identified and are presumed to be precursors. If released into the circulation, these peptides, collectively called atrial natriuretic factor (ANF), may play a significant part in blood-pressure homeostasis, regulation of extracellular fluid volume and as antagonists to the hypertensive effects of the renin-angiotensin system and other hormonal and neurotransmitter systems. We describe here the isolation and characterization of rat atrial cDNA clones which encode ANF. Nucleotide sequence analysis shows that auriculin corresponds to the 25 amino acids located close to the C-terminus of a 152-amino acid ANF precursor. Analysis of the in vitro translation products of precursor ANF mRNA suggests that multiple forms of the precursor may exist.