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Biomedical subjects

J Chanard

Publications and source records attributed to J Chanard.

At least 109 records · Page 6Linked to original sources

Purine biosynthesis de novo by lymphocytes in gout.

1. A method of measurement in vitro of purine biosynthesis de novo in human circulating blood lymphocytes is proposed. The rate of early reactions of purine biosynthesis de novo was determined by the incorporation of [14C]formate into N-formyl glycinamide ribonucleotide when the subsequent reactions of the metabolic pathway were completely inhibited by the antibiotic azaserine. 2. Synthesis of 14C-labelled N-formyl glycinamide ribonucleotide by lymphocytes was measured in healthy control subjects and patients with primary gout or hyperuricaemia secondary to renal failure, with or without allopurinol therapy. 3. The average synthesis was higher in gouty patients without therapy than in control subjects, but the values obtained overlap the normal range. In secondary hyperuricaemia the synthesis was at same value as in control subjects. 4. These results are in agreement with the inconstant acceleration of purine biosynthesis de novo in gouty patients as seen by others with measurement of [14C]glycine incorporation into urinary uric acid.

Adult↗

[De novo purine biosynthesis. In vitro measurement in hyperuricemia (author's transl)].

De novo purine biosynthesis has been investigated in circulating blood lymphocytes in vitro. N-formyl-glycinamide ribonucleotide (FGAR) has been mesured using 14C-formate incorporation in the presence of azaserine, a metabolic inhibitor blocking the metabolical pathway at the level of FGAR synthesis. Such a synthesis was measured in 20 healthy controls, 24 patients with primary gout (11 on allopurinol therapy) and 26 patients with chronic renal failure and secondary hyperuricemia (8 on allopurinol therapy). Among gouty patients without allopurinol therapy, FGAR synthesis was normal in 5 and increased in the others. FGAR synthesis was decreased in patients with renal failure whatever the therapy. However, FGAR synthesis remained increased in patients with a primary gout complicated with renal insufficiency. The test we propose for de novo purine biosynthesis measurement is simple and of value to analyse the patho-physiology of hyperuricemia and its therapy. The test allows an acurate discrimination between primary and secondary hyperuricemia in the presence of renal insufficiency.

Adult↗

Effect of parathyroid hormone and volume expansion on jejunal calcium, sodium, and water transport in the rat.

The effects of PTH on jejunal calcium, sodium, and water transport were studied in the rat in situ. In TPTx rats, as well as in normal rats, bovine PTH induced a decrease in net calcium, sodium, and water absorption. Additionally, lumen-to-plasma calcium flux was found decreased in both groups. Stimulation of endogenous PTH secretion by calcium-poor hyperoncotic albumin resulted in a similar decrease in net calcium, sodium, and water absorption. It is suggested that PTH has a direct inhibitory effect on jejunal calcium, sodium, and water absorption.

Albumins↗

Noninvasive experimental determination of the individual kidney filtration fraction by means of a dual-tracer technique.

A noninvasive method for measurement of the individual kidney filtration fraction (FF) is presented, based on an analysis of the early rise of the kidneys' time-activity curves obtained after simultaneous injection of tubular [131I] ortho-iodohippurate and glomerular (Tc-99m DTPA) tracers. The analysis is based on the assumption that an insignificant amount of tracer leaves the kidney during the first few moments following injection. Therefore the kidney activity during this period is directly proportional to the integral of the blood (heart) activity. The dual-tracer technique allows the direct calculation of the ratio of glomerular to tubular clearances, i.e., the FF. In vivo studies were performed on 12 dogs, including normals as well as others with acute ureteral ligation or Benemid-induced tubular blockade. The calculated FF correlated well with the FF obtained from single-shot clearances performed simultaneously. We conclude that the FF can be calculated directly for each kidney, noninvasively, from the early part of the tubular and glomerular time-activity curves by noninvasive external detection.

Animals↗

Effects of saline loading on jejunal absorption of calcium, sodium, and water, and on parathyroid hormone secretion in the rat.

To investigate whether intestinal calcium absorption parallels that of sodium following extra-cellular fluid volume expansion, the effects of saline loading on intestinal transport of calcium, sodium and water were studied in rats by perfusing jejunal loops in situ. After calcium-free saline infusion net calcium absorption was reversed similar to that of sodium and water and net secretion occurred. Concurrently, blood-to-lumen (b-l) calcium flux, measured using 45Ca, increased significantly (P less than 0.001). Following expansion with calcium-containing Ringer a similar reversal of net calcium, sodium and water flux was also observed. Again the b-l calicum flux increased but to a significantly lesser extent (P less than 0.05). Plasma ionized calcium remained unchanged after calcium-rich Ringer loading, but decreased significantly (P less than 0.001) when calcium was omitted from the solution. Plasma immunoreactive parathyroid hormone unchanged after expansion with the calcium containing solution but increased following calcum-free infusion. It is concluded that after extracellular fluid volume expansion: 1. net jejunal calcium absorption is decreased; 2. the decrease parallels that of sodium and water; 3. b-l calcium transport is enhanced to a greater degree of calcium-free Rnger infusion than by a calcium-rich solution. This difference could be the result of increased parathyroid hormone secretion.

Animals↗

[Demonstration of a microtubule protein (tubulin) in swine parathyroid cytosol].

A cytosolic colchicine-binding protein has been studied in Porcine parathyroid glands. The molecular weight of this protein is 110,000 dalton with a 6 S sedimentation constant. Its colchicine affinity is 1.3 X 10(6) l/mole at 37 degrees C. Polymerization-depolymerization kinetics and vinblastin sulfate-induced precipitation are the same as that of a tubulin.

Animals↗

1 alpha hydroxycholecalciferol and 25 hydroxycholecalciferol in renal bone disease.

Four microgrammes of 1-alpha-hydroxycholecalciferol (1-alpha-OH D3) or 200 mug of 25-hydroxycholecalciferol (25-OH D3) were given orally every other day respectively to 10 uraemic patients (8 on chronic haemodialysis) for 1-12 weeks and to 3 patients on chronic haemodialysis for 4-8 weeks. A transilial bone biopsy and serial evaluation of serum immunoreactive PTH (iPTH) calcium phosphate and alkaline phosphatase were performed before and at the end of therapy. Both 1-alpha-OH D3 and 25-OH D3 (the latter at a 50 times higher dose) were able to depress hyperparathyroidism in two-thirds of the cases and to consistently improve the mineralisation defect. In no case did iPTH or the bone histomorphometric parameters return to normal, so that long term evaluation of these two drugs is warranted.

Absorption↗

Kinetics of HBs antigen in man.

The metabolism of HBs Antigen had been studied in three human volunteers. One had chronic hepatitis and two were "silent carriers". The HBs Antigen had been isolated and purified from the plasma of each of the three subjects and, after iodination, reinjected to the same donor. The parameters of plasma kinetics of 131I HBsAg have been analyzed according to a two compartmental model on the basis of the radioactivity of TCA precipitate (TP) and immunoprecipitate (IP). The fast initial volume of distribution was approximately equal in the three subjects (46.6 ml/kg). The metabolic clearance rate (MCR) of IP was the very same in two subjects but is four times higher in one of the silent carrier. The total renewal time (TRT) was about 3.3 days. Assuming that the HBs Antigen extraction was of the order of 65% the plasma HBs Antigen concentration per liter of plasma would be 12 and 53 mg/liter fot two silent carriers and 61 mg/liter for the patient with chronic hepatitis. The radioactive efflux from the model (calculated as IP.MCR multiplied by HBs Antigen concentration) was identical for the two silent carriers adn 50% higher in the patient with chronic hepatitis. This increase possibly reflects an increased synthesis of HBs Antigen in the patient with chronic hepatitis. The cumulative urinary radioactivity when added to the whole body counting demonstrated that radioactivity was excreted solely in the urine. The ratio of organ counting to precordium counting did not vary significantly with time in all subjects.

Adult↗