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Biomedical subjects

J R Aprille

Publications and source records attributed to J R Aprille.

At least 55 records · Page 3Linked to original sources
PubMed1983

Mitochondrial cytochrome deficiency presenting as a myopathy with hypotonia, external ophthalmoplegia, and lactic acidosis in an infant and as fatal hepatopathy in a second cousin.

Fatal infantile mitochondrial myopathy with lactic acidosis, morphologically abnormal mitochondria, deficient cytochromes aa3 and b, and a Fanconi-like aminoaciduria has been described. We report two infants, second cousins, with a similar fatal mitochondrial disorder, the cytochrome deficiency limited to skeletal muscle in one child and to liver in the other. The first child at 3 months of age had weight loss, hypotonia, external ophthalmoplegia, and a severe lactic acidosis with a high lactate/pyruvate ratio. Electron microscopy of muscle showed marked proliferation of enlarged mitochondria, many containing concentric rings of cristae. In skeletal muscle mitochondria, cytochromes aa3 and b were not detectable but cytochrome cc was found to be normal by spectroscopy. Cytochrome c oxidase activity was less than 1% of normal. Mitochondria from kidney, liver, heart, lung, and brain examined postmortem had normal cytochromes and preserved cytochrome c oxidase activity. The second cousin at 5 months of age had weight loss and hepatomegaly but no systemic lactic acidosis. Liver biopsy showed hepatocytes packed with enlarged mitochondria. The liver mitochondria showed deficient cytochromes aa3 and b postmortem, and cytochrome c oxidase activity was less than 10% of normal. Kidney mitochondria had normal cytochromes. Muscles was not studied. The mitochondrial abnormality in the two cousins presumably is related. Unexplained are the mode of genetic transmission or environmental exposure and the apparent involvement of a single different organ in each child.

Acidosis↗
PubMed1983

Chronic progressive external ophthalmoplegia (CPEO): clinical, morphologic, and biochemical studies.

We studied skeletal muscles from eight chronic progressive external ophthalmoplegia patients with ragged-red fibers (group A), five CPEO patients without ragged-red fibers (group B), and five controls. The EM morphometric fraction of structurally abnormal mitochondria was increased in group A, and there was a similarly increased fraction of normal-appearing mitochondria in group B. State 3 respiration and uncoupled respiration were severely decreased in both groups. The morphometric mitochondrial fraction and respiratory functions were inversely related in all three groups. The cytochrome content in group A was normal; cytochromes b and cc1 were decreased in group B. These studies point to a central role of mitochondrial dysfunction in all types of CPEO, but the basic abnormalities remain to be elucidated.

Adult↗
PubMed1982

Adenine nucleotide pool size, adenine nucleotide translocase activity, and respiratory activity in newborn rabbit liver mitochondria.

The adenine nucleotide content (ATP+ADP+AMP) of newborn rabbit liver mitochondria was 6.0 +/- 0.5 nmol/mg mitochondrial protein at birth, increased rapidly to 14.5 +/- 1.7 nmol/mg protein by 2 h postnatal, peaked at 6 h, then decreased gradually to 7.8 +/- 0.6 nmol/mg protein by 4 days postnatal. There was a strong positive correlation (r = 0.82) between the total adenine nucleotide pool size and adenine nucleotide translocase activity in these mitochondria. In contrast, glutamate + malate-supported State 3 respiratory rates remained constant from birth through the first week of life. State 4 rates also remained constant, as did the respiratory control index and uncoupled respiratory rates. The following conclusions are suggested: (1) The maximum rate of translocase activity is limited by the intramitochondrial adenine nucleotide pool size. (2) In newborn rabbit liver mitochondria, the State 3 respiratory rate is not limited by either the adenine pool size or the maximum capacity for translocase-mediated adenine exchange. (3) In contrast to rat, rabbit liver mitochondria are fully functional at birth with regard to respiratory rates and oxidative phosphorylation. (4) The rapid postnatal accumulation fo adenine nucleotides by liver mitochondria, now documented in two species, may be a general characteristic of normal metabolic adjustment in neonatal mammals.

Adenine Nucleotides↗
PubMed1981

Acute postnatal regulation of pyruvate carboxylase activity by compartmentation of mitochondrial adenine nucleotides.

The total adenine nucleotide content of the mitochondrial matrix increases 3--4-fold within a few hours of birth in rat liver. This provides a mechanism for the acute postnatal regulation of pyruvate carboxylase, which is located in the matrix compartment and which requires ATP as a substrate. The sudden increase in pyruvate carboxylase activity is proposed to account for a rapid 4--5-fold increase in the gluconeogenic rate of the newborn rat.

Adenine Nucleotides↗
PubMed1979

Adenylate cyclase after burn injury: resistance to desensitization by catecholamines.

In vivo injection of isoproterenol(IPR) (4 mg/kg) in normal rats caused fat cell adenylate cyclase to become desensitized to stimulation by IPR in vitro. In contrast, adenylate cyclase from tissues of burn-injured rats (20% body surface, full-thickness scald) remained fully responsive to stimulation by IPR for several days after injury even though catecholamine excretion was elevated more than twofold. Furthermore, fat cell adenylate cyclase from burn-injured animals was not desensitized after acute in vivo IPR injections, whereas adenylate cyclase from the shams did become desensitized after acute IPR injections. To determine whether the apparent resistance to desensitization in burn-injured rats might be an adaptation to the chronic elevation of catecholamines that follows burn injury, two other rat models in which catecholamines are chronically elevated were studied: one was produced by a twice daily schedule or IPR (1 mg/kg) injections for 3 weeks; the other by 3 weeks' cold exposure (0--4 degrees C). As had been observed in burn injury, adenylate cyclase remained fully responsive to IPR in both models, and adenylate cyclase from the cold-acclimated rats was resistant to desensitization by acute injections of IPR. It therefore seems likely that chronic elevations of catecholamines evoke regulatory mechanisms in target cells to circumvent the desensitizationwhich would otherwise occur consequent to acute exposures to catecholamines. In burn injury this may result in an inadvertent adaptation which contributes to hypermetabolism.

Adenylyl Cyclases↗
PubMed1977

Multiple forms of brain adenylate cyclase: stimulation by Mn2+.

Mn2+-stimulated adenylate cyclase (ATP pyrophosphate-lyase-(cyclizing), EC 4.6.1.1) activity in detergent solubilized preparations from mouse brain. While NaF-stimulated activity was decreased by both solubilization and storage at 0--4 degrees C, the ability of the enzyme to be stimulated by Mn2+ was maintained for up to one week. By including Mn2+ in the assay of adenylate cyclase in gel fractions after isoelectric focusing, two distinct peaks of enzyme activity (pI1 - 5.8, pI2 = 6.4) were detected, suggesting the existence of more than one type of catalytic subunit in mouse brain cell membranes.

Adenylyl Cyclases↗