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Biomedical subjects

D Francois

Publications and source records attributed to D Francois.

8 recordsLinked to original sources
PubMed1992

Impairment of mitochondrial 5-aminolevulinic acid synthase activity in Gunn rat liver.

Gunn rats are characterized by hereditary hyperbilirubinemia and a decrease, when compared to Wistar rats, in hepatic heme pool size which could result from an alteration of mitochondrial functions. Unconjugated bilirubin present in Gunn rat liver did not modify either the ultrastructural morphology or oxidative metabolism of the mitochondria as compared to those in Wistar rat liver. However, 5-aminolevulinic acid synthase activity is reduced by nearly 40% in Gunn rat liver mitochondria, thus explaining the reduced size of the hepatic heme pool.

5-Aminolevulinate Synthetase↗
PubMed1991

Deletions of mitochondrial DNA in Kearns-Sayre syndrome and ocular myopathies: genetic, biochemical and morphological studies.

Genetic, biochemical and morphological investigations were conducted on skeletal muscle mitochondria from 6 cases of ocular myopathy: 4 cases with Kearns-Sayre syndrome (KSS) and 2 with chronic progressive external ophthalmoplegia. All of these 6 cases showed mitochondrial DNA (mtDNA) deletions in addition to normal sized DNA in the quadriceps muscle. The deletions ranging from 3 to 8 kbp were also mapped between nucleotides 5500 and 16000 by Southern blot. The deleted genes encoded for some subunits of complexes I, IV, V and 5-10 tRNAS. The boundaries of the deletions have been sequenced in three patients. Five patients had mitochondrial respiratory chain deficiency in complex I as shown by the low oxygen consumption in isolated mitochondria using three NAD(+)-linked substrates. Mitochondria with an abnormal ultrastructure were also observed in 2 cases. A good relationship between the cytochrome c oxidase deficiency and the amount of deleted mtDNA was shown in our present investigations.

Adult↗
PubMed1990

Evidence of mitochondrial impairment during cardiac allograft rejection.

NADH laser fluorimetry and mitochondrial oxigraphy were used to study myocardial oxidative energy metabolism during cardiac allograft rejection. Heterotopic cardiac transplantation was performed on Lewis rats; allografts (with Fischer rat donors) were compared with isografts (with Lewis rat donors). In vivo and in vitro assays were performed six days after transplantation. Myocardial NADH fluorescence was recorded in vivo from grafted hearts, at baseline; during brief, complete ischemia; and during reperfusion. Oxygen consumption of mitochondria isolated from both native and grafted hearts was determined. Neither baseline levels nor maximum ischemic levels of NADH fluorescence (F0 = k[NADH]) were found to be significantly different between allografts (0.45 +/- 0.05 to 0.87 +/- 0.10) and isografts (0.45 +/- 0.04 to 1.11 +/- 0.05). During recovery, the rate of fluorescence decrease was significantly lower in allografts than in isografts (0.024 +/- 0.001 vs. 0.038 +/- 0.002 delta F0.s-1, P less than 10(-3], indicating a lower rate of NADH reoxidation. In the presence of malate and glutamate substrates, mitochondrial O2 consumption was significantly lower in allografts than in isografts (30 +/- 9 vs. 100 +/- 15 nanoatoms O2. min-1.mg prot-1, P less than 10(-2]. These results indicate that mitochondrial oxidative metabolism was impaired during the rejection process. Such energy production disturbances may contribute to the dysfunction of rejecting hearts.

Animals↗
PubMed1989

Low basal thyrotropin with normal thyroid function in primary hyperparathyroidism.

TSH serum levels and thyroid function in 32 patients with primary hyperparathyroidism and hypercalcemia were compared to those of 30 age and sex-matched normal subjects. Serum T3 and T4 concentrations in hyperparathyroidism were not different from normal. However, basal serum TSH concentrations measured with an ultrasensitive immunoradiometric assay were significantly lower than normal (1.09 +/- 0.49 vs 2.06 +/- 0.85 mU/l, p less than 0.001). In hyperparathyroidism, TSH, but not T4 or T3, was negatively correlated with serum calcium, not with iPTH. The increase in TSH (delta TSH) 30 min after the iv injection of TRH was also significantly blunted in patients with primary hyperparathyroidism; delta TSH was highly correlated with basal TSH in hypercalcemic patients. The basal TSH concentration was higher and no longer different from normal (1.70 +/- 1.2 mU/l) 2 to 12 months after removal of the parathyroid adenoma, when serum calcium was normalized, whereas T3 and T4 did not change. A low basal TSH with normal T4 and low T3 was found in 13 patients with hypercalcemia of malignancy. In these patients, TSH increased after treatment of hypercalcemia with 3-amino-l,hydroxypropylidene-1, 1-bisphosphonate, whereas T4 did not change. The results suggest that the set point of pituitary thyroid feedback control could be decreased in chronic hypercalcemia and that hypercalcemia could render the thyroid more sensitive to TSH.

Adenoma↗