Phosphate homeostasis is controlled in part by absorption from the intestine, and reabsorption in the kidney. While the effect of Vitamin D metabolites on enterocytes is well documented, in the current study we assess selected responses in primary cultures of kidney cells. Time course studies revealed a rapid stimulation of phosphate uptake in cells treated with 1,25(OH)(2)D(3), relative to controls. Dose-response studies indicated a biphasic curve with optimal stimulation at 300 pM 1,25(OH)(2)D(3) and inhibition at 600 pM seco-steroid. Antibody 099--against the 1,25D(3)-MARRS receptor - abolished stimulation by the steroid hormone. Moreover, phosphate uptake was mediated by the protein kinase C pathway. The metabolite 24,25(OH)(2)D(3), which was found to inhibit the rapid stimulation of phosphate uptake in intestinal cells, had a parallel effect in cultured kidney cells. Finally, the 24,25(OH)(2)D(3) binding protein, catalase, was assessed for longer term down regulation. In both intestinal epithelial cells and kidney cells incubated with 24,25(OH)(2)D(3) for 5-24h, both the specific activity of the enzyme and protein levels were decreased relative to controls, while 1,25(OH)(2)D(3) increased both parameters over the same time periods. We conclude that the Vitamin D metabolites have similar effects in both kidney and intestine, and that 24,25(OH)(2)D(3) may have effects at the level of gene expression.

There is increasing evidence that the vitamin D metabolite, 24,25-dihydroxyvitamn D-3 (24,25(OH)(2)D-3) has endocrine actions. In the crrent work, we report that an endogenous binding protein for 24,25(OH)(2)D-3 is catalase, based on sequence analysis of the isolated protein. An antibody (Ab 365) generated against equivalent protein recognized bovine catalase and a 64 kDa band in subcellular fractions of chick intestine. A commercially available anti-catalase antibody reduced specific [H-3]24,25(OH)(2)D-3 binding in subcellular fractions of chick intestine by greater than 65%, relative to the same fractions treated with art unrelated antibody (Ab 099). The same commercially available anti-catalase was able to block the inhibitory actions of 24,25(OH)(2)D-3 Oil P-32 uptake in isolated intestinal epithelial cell suspensions. We subsequently characterized binding of steroid to commercially available catalase, and found that between 0 and 5 nM of enzyme added to subcellular fraction P-2 (20,000g, 10-min post-nuclear pellet) resulted in a linear increase in the amount of [H-3]24,25(OH)(2)D-3 specifically bound. Additional studies indicated that 25(OH)D-3 was an effective competitor for binding, whereas 1,25(OH)(2)D-3 only poorly displaced [H-3]24,25(OH)(2)D-3. Saturation analyses with added catalase yielded a physiologically relevant affinity constant (K-D=5.6 +/- 2.7 nM) and a B-max = 209 +/- 34 fmols/mg protein, comparable to previous studies using purified basal lateral membranes or vesicular fractions. Moreover, in a study on subcellular fractions isolated from chickens of varying ages, we found that in females, both specific [H-3]24,25(OH)(2)D-3 binding and catalase activity increased from 7-to58-week-old birds,whereas in males, elevated levelsof both parameters were expressed in preparations of 7- and 58-week-old birds. The data suggest that signal transduction may occur through modulation of hydrogen peroxide production.

Complementary therapies attract considerable media attention and previous surveys of members of an asthma patient organisation suggested that their use by those with asthma was commonplace. This report concerns a study of a stratified cross section of the asthma population designed to give a more representative insight into current usage of complementary therapies. A sift questionnaire was used to identify those with asthma and 785 of those so identified undertook a semi-structured face-to-face interview. Only 6% of the study population were current users of complementary therapies with use being more common amongst those who expressed most concern regarding their current medication. Low use of complementary therapies may well reflect satisfaction with current management and suggests that previous surveys may have been unrepresentative of a more balanced population of those with asthma.

We report a rare example of inversion (14)(q11q32) in childhood T-ALL and its further involvement in a subsequent translocation. We discuss the possible clinical significance of inv(14) in childhood T-ALL.

Using a standardised block technique, the microscopic lactate dehydrogenase-nitro blue tetrazolium (LDH-nitro BT) and conventional haematoxylin and eosin staining methods were used to investigate the presence of myocardial infarction in a series of fifty forensic autopsies. The microscopic LDH-nitro BT method was found to be reliable; however, it did not reveal the presence of myocardial infarction in any of the cases where this had not been suspected.