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Biomedical subjects

R C Sengers

Publications and source records attributed to R C Sengers.

At least 109 records · Page 6Linked to original sources
PubMed1985

Investigation of mitochondrial metabolism in small human skeletal muscle biopsy specimens. Improvement of preparation procedure.

A method is presented which allows the investigation of almost the complete mitochondrial content of small human skeletal muscle biopsy specimens. Thorough mechanical disruption with a chopper apparatus results in the release of about 50% of the mitochondrial content. Subsequent treatment of the 600 x g sediment with trypsin releases another 30% of the total mitochondrial population. The biochemical characteristics of the two mitochondrial fractions obtained in these two successive steps have been compared. No obvious differences could be established. The procedure is well suited for biochemical investigation of muscle biopsy specimens from patients suspected of suffering from a mitochondrial myopathy.

Adenosine Diphosphate↗
PubMed1985

Computerized calculation of in vitro generation of ATP and creatine phosphate induced by respiration in human muscle mitochondria.

A computer program is presented which calculates the action of adenylate kinase and creatine kinase during the process of adenosine-5'-triphosphate generation by the mitochondria in human skeletal muscle 600 X g supernatants. The results show that the mass action ratios of the two kinase reactions are not influenced by incubation time or decreased rate of oxidative phosphorylation as a result of mitochondrial dysfunction. The program is useful for establishing optimum initial adenosine-5'-diphosphate and creatine concentrations in the assay medium.

Adenosine Triphosphate↗
PubMed1985

Hypertrophic cardiomyopathy associated with a mitochondrial myopathy of voluntary muscles and congenital cataract.

Structurally abnormal mitochondria were found in skeletal muscle cells from a woman with hypertrophic cardiomyopathy and myopathy of voluntary muscles associated with congenital cataracts. Moderate exercise resulted in lactic acidosis. Oxidation of pyruvate and other substrates and the production of adenosine triphosphate were normal in vitro. A younger brother of the patient had had congenital cataract and had died from hypertrophic obstructive cardiomyopathy.

Adolescent↗
PubMed1984

Elevated urine, blood and cerebrospinal fluid levels of uracil and thymine in a child with dihydrothymine dehydrogenase deficiency.

In the urine of a child with unexplained convulsions large amounts of uracil and thymine were detected by gas chromatography. Identification was performed by coupled gas chromatography-mass spectrometry. Quantitation of the urinary excretion by means of a sensitive high-performance liquid chromatographic (HPLC) method revealed a 1000-fold elevation compared to normal. Serum and cerebrospinal fluid levels of the two pyrimidine bases were about a hundred times higher than normal. In fibroblasts the activity of dihydrothymine dehydrogenase was determined by measuring the conversion of radioactive labelled thymine to dihydrothymine with HPLC of the reaction mixture. In the patient's cells a complete deficiency of dihydrothymine dehydrogenase activity was found. Our patient is the first case described with such a proven enzyme deficiency.

Child↗
PubMed1984

Deficiency of cytochromes b and aa3 in muscle from a floppy infant with cytochrome oxidase deficiency.

A girl was presented suffering from generalised weakness and cardiorespiratory insufficiency. She succumbed at the age of 5 months. Lactate levels were elevated in serum, cerebrospinal fluid and urine. Histopathological examination revealed a mitochondrial myopathy. In muscle tissue the cytochrome oxydase activity was strongly reduced. The content of cytochromes b and aa3 was very low. At autopsy a cardiomyopathy was found.

Acidosis↗
PubMed1984

In vivo induced malignant hyperthermia in pigs. II. Metabolism of skeletal muscle mitochondria.

The biochemical characteristics of skeletal muscle mitochondria of malignant hyperthermia (MH) susceptible Dutch Landrace pigs have been investigated before and during an MH attack, induced in vivo by halothane plus succinylcholine. The muscle homogenates have a decreased capacity to synthesize ATP and creatine phosphate during the MH period. Muscle mitochondria prepared from susceptible pigs in an MH period consume less oxygen than do mitochondria isolated before the attack, or mitochondria from control pigs during the challenge. The oxidative phosphorylation is not uncoupled during the critical period. The production of CO2 indicates that the in vitro measured capacity of the MH muscle mitochondria correctly reflects the in vivo condition during the MH attack. The restricted synthesis may be caused by a factor, finding expression in the mitochondria themselves, and obtained or activated during the MH attack.

Adenosine Triphosphate↗
PubMed1984

In vivo induced malignant hyperthermia in pigs. III. Localization of calcium in skeletal muscle mitochondria by means of electronmicroscopy and microprobe analysis.

Biceps femoris muscle biopsies of malignant hyperthermia susceptible (MH+) and non-susceptible (MH-) Dutch Landrace pigs were studied ultrastructurally, and exchangeable calcium was demonstrated, using the antimonate precipitation technique in combination with electron probe x-ray microanalysis. Biopsies were taken before and during the administration of halothane-plus-succinylcholine and after dantrolene sodium treatment of the animals. MH+ muscle, taken before the MH triggering, showed a high proportion (about 35%) of cells with supercontraction. Both MH+ and MH- muscle had broad but nearly identical ranges of cell diameter. Core-like structures were occasionally present in muscle from MH+ pigs. Muscle mitochondria from the MH+ pigs accumulated large amounts of calcium in their matrix compartment during the halothane-plus-succinylcholine induced MH crisis. This calcium loading in the course of time caused swelling and structural damage to the mitochondria. Skeletal muscle mitochondria from MH- pigs did not show such a reaction pattern on challenge with halothane and succinylcholine. It is concluded that in MH+ pigs the challenge brings about an increase in myoplasmic free calcium, which is predominantly due to calcium influx from the extracellular fluid. This rise in cytosolic calcium causes the mitochondria to accumulate the cation in an energy-dependent way. These findings are discussed in relation to the diverging halothane and caffeine contraction responses of aerobic type I and anaerobic type II muscle fibres.

Animals↗
PubMed1984

[Mitochondrial myopathy associated with cytochrome oxidase deficiency].

Six patients are described in whom a deficiency of cytochrome oxidase in muscle tissue was found. Four patients suffered from the syndrome of 'floppy babies' with profound hypotonia, muscle weakness and failure to thrive. They died within the first 6 months of life. Two patients suffered from Leigh's and Alpers' syndrome, respectively. In all patients lactate level was elevated in one or more body fluids, whereas in 4 patients a generalized amino-aciduria was found. With electronmicroscopy structurally abnormal mitochondria were seen in the muscle of 5 out of the 6 patients.

Cytochrome-c Oxidase Deficiency↗
PubMed1983

Demyelination and disturbed metabolism of pyruvate: a case report.

A patient with demyelination is described. Lactate levels were elevated in serum, urine, and cerebrospinal fluid. A decreased pyruvate oxidation rate due to a pyruvate dehydrogenase complex deficiency was demonstrated in muscle and cultured fibroblasts. In muscle mitochondria no structural abnormalities were seen. The clinical course was progressive and the patient died at the age of 6 months.

Carbohydrate Metabolism, Inborn Errors↗
PubMed1983

A mitochondrial myopathy with a defective respiratory chain and carnitine deficiency.

A boy presented suffering from generalised weakness, exercise intolerance and lactic acidosis. The weakness became evident at 2 years. A cerebral CT-scan showed cerebellar atrophy and central and peripheral atrophy of both hemispheres. With trichrome staining about 20% of the muscle fibres showed large areas containing red-staining granular material. Electron microscopic examination showed that this material consisted of areas of mitochondrial proliferation, most of the mitochondria having abnormal ultrastructural characteristics. Pyruvate dehydrogenase complex and citric acid cycle activities were determined by measuring 14CO2 production from various labelled substrates. Diminished oxidation rates were found with the patient's muscle homogenate for all substrates tested, indicating a defect in the respiratory chain. The cytochromes were present in normal quantities. Succinate cytochrome c reductase activity was very decreased. Carnitine concentration was decreased in serum and in muscle as well.

Brain↗
PubMed1983

[A patient with persistent hyperlysinemia].

A 3 year old mentally retarded boy with convulsions and a disturbed motor, speech and social development is presented. A persistent hyperlysinaemia, lysinuria and saccharopinuria was found. Treatment with a diet restricted in lysine seems favourable.

Amino Acid Metabolism, Inborn Errors↗
PubMed1982

[Isovaleric acidemia: identical biochemical picture in 3 patients with variable clinical manifestations].

Three patients are described with different forms of isovaleric acidemia: a girl with the neonatal form and two brothers with an intermittent form. In all three patients the biochemical aspects are identical: Considerable amounts of metabolites of isovaleric acid, especially isovalerylglycine, are secreted with the urine. In the patients' cultured fibroblasts leucine oxydation is greatly depressed. The clinical presentation of the younger brother prompted to a direct search for a metabolic defect. After diagnosing an isovaleric acidemia in the younger brother, investigations on the presence of the same defect were performed in the elder brother too, though he did not show clinical symptoms. As a result, also isovaleric acidemia was found. It is concluded that sibs of patients with a proven inborn error of metabolism have to be studied too for the presence of the same defect. In all patients, especially in the girl with the neonatal form of isovaleric acidemia diet therapy had a beneficial effect on the further course of the disease.

Amino Acid Metabolism, Inborn Errors↗
PubMed1981

Progressive infantile poliodystrophy. Association with disturbed pyruvate oxidation in muscle and liver.

Progressive infantile poliodystrophy (Alpers' disease) is associated with abnormalities in pyruvate metabolism or in cell mitochondria. A 3-year-old-boy had a severe and rapidly progressive neurologic disorder characterized by psycho-motor retardation, tetraparesis, ataxia, and myoclonic jerks, the illness being exacerbated during periods of infection. Lactate concentration in CSF was elevated. Histopathologic studies revealed lipid storage in liver and muscle. Autopsy showed a progressive infantile poliodystrophy. Mitochondrial abnormalities were found in heart muscle. Biochemical studies of muscle and liver tissue suggested a disturbance in nicotinamide adenine dinucleotide (reduced form) oxidation.

Child, Preschool↗
PubMed1981

Estimation of energy metabolism in human skeletal muscle homogenate as a diagnostic aid.

A method is presented for the in vitro testing of the energy metabolism of human skeletal muscle. The levels of creatine phosphate, ATP, ADP and AMP, which are defined by the activity of many enzyme system, are measured after incubation of the muscle homogenate with various substrates in the presence or absence of specific inhibitors. Detection of abnormal metabolite concentrations is important for diagnosis of patients with myopathic syndromes.

Adenine Nucleotides↗