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Biomedical subjects

D Francois

Publications and source records attributed to D Francois.

17 recordsLinked to original sources
PubMed1995

Clinical, biochemical, and molecular analysis of a maternally inherited case of Leigh syndrome (MILS) associated with the mtDNA T8993G point mutation.

We report a new case of Leigh disease (subacute necrotizing encephalomyelopathy) in a girl with mitochondrial DNA (mtDNA) mutation in the ATPase6 gene at nucleotide position 8993. Sequence analysis of mtDNA revealed a T-to-G transversion at nucleotide position 8993 in the ATPase6 gene. Southern blot restriction analysis of patient muscle mtDNA showed only a mutant pattern for the mutation 8993. Molecular analysis of seven subjects from the family showed that except for the father they all carried the 8993 mtDNA mutation in all studied tissues, with high percentages in the two symptomatic children and even in one asymptomatic boy.

Brain↗
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↗
PubMedDate not supplied

Residual area at risk after anterior myocardial infarction: are ST segment changes during coronary angioplasty a reliable indicator? A comparison with technetium 99m-labeled sestamibi single-photon emission computed tomography.

BACKGROUND: The aim of this study was to assess whether, after anterior myocardial infarction, ST segment changes during percutaneous transluminal coronary angioplasty (PTCA) of the left anterior descending coronary artery correlated with the amount of ischemic myocardium in the area at risk, measured with 99mTc-labeled sestamibi single-photon emission computed tomography (SPECT) during balloon inflation. METHODS AND RESULTS: Quantitative continuous monitoring of the ST segment was performed during PTCA of the left anterior descending coronary artery in 11 patients, and corresponding SPECT imaging was compared with a rest acquisition performed before PTCA. SPECT was quantified by a bull's-eye analysis according to main criteria: (1) the planimetered defect size during PTCA as an indicator of the size of the area at risk, (2) the change in the pathologic/normal area count ratio in the area at risk as an index of the severity of ischemia, and (3) the difference between the size of the defect during PTCA and at baseline. ST segment changes were correlated to the variation in pathologic/normal area count ratio (19% +/- 14%; r = 0.61; p < 0.05) but not to the sizes of the scintigraphic defects. CONCLUSION: ST segment changes induced by occlusion of the infarct-related coronary artery during PTCA are related mostly to the severity of ischemia rather than to the size of the area at risk.

Adult↗