Mitochondrial myopathies: multiple enzyme defects in the respiratory chain.
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Adolescent↗
Biomedical subjects
J C Fischer
Publications and source records attributed to J C Fischer.
Disorders of the mitochondrial respiratory chain: clinical manifestations and diagnostic approach.
The clinical identification of patients with defects in the mitochondrial respiratory chain is almost impossible. We describe screening tests that should be performed in order to select those patients in whom a skeletal muscle biopsy should be carried out for more specific biochemical assays. The importance of performing in vivo function tests is stressed. The biochemical diagnosis in disorders of the respiratory chain is presented and the application of immunological methods discussed.
Biopsy↗
Mitochondrial encephalomyopathy. Association with an NADH dehydrogenase deficiency.
A 17-year-old patient had a progressive hypokinetic-rigid syndrome and several other signs and symptoms that indicated central nervous system involvement. Biochemical studies revealed a reduced form of nicotinamide-adenine dinucleotide dehydrogenase deficiency in skeletal muscle. Clinical signs and symptoms, and their association with an established defect of energy metabolism, led us to classify this disorder as a mitochondrial encephalomyopathy of Leigh's type.
Adolescent↗
[Aphthae and oral aphthosis. Current concepts].
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Behcet Syndrome↗
Estimation of NADH oxidation in human skeletal muscle mitochondria.
Assay procedures are described for the detection of defects in the process of NADH oxidation by the respiratory chain in human skeletal muscle biopsy specimens. The procedures allow determination of rotenone-sensitive NADH: O2 oxidoreductase and NADH: ubiquinone-1 oxidoreductase activity not only in isolated mitochondria but also in post-nuclear supernatants. The use of ferricyanide as electron acceptor for estimation of NADH dehydrogenase activity is inadequate when only applied on a disrupted mitochondrial preparation.
Cytochrome c Group↗
Waveform analysis applied to laser Doppler flowmetry.
Laser Doppler flowmetry (LDF) has been found useful in monitoring free flaps. In the present study, waveform analysis has been applied to the LDF waveform. Waveform changes were investigated in the microcirculation during varying degrees of arterial or venous occlusion in the saphenous island and flap of the dog and the human digit. The quantitative analysis of laser Doppler flowmetry waveform allows for the diagnosis of arterial occlusion or venous occlusion and their differentiation.
Animals↗
Dynamic computer tomography determining the patency of buried free flaps.
Numerous methods exist for monitoring the patency of cutaneous free flaps. Monitoring the patency of microvascular anastomosis in buried free flaps are limited. The present case report is of a 39-year-old female with Rhomberg's disease who underwent an abdominus rectus muscle free flap to correct the contour deformity of the right face. Dynamic CT scan was performed on the sixth postoperative day. Plots of the rate of change of density of the free flap were compared to an adjacent muscle of the face. Dynamic CT scanning provides a high degree of resolution of the free flap, the ability to examine the entire free flap, and the ability to determine the patency of buried free flap.
Adult↗
A mitochondrial encephalomyopathy: the first case with an established defect at the level of coenzyme Q.
A patient is presented who had therapy-resistant epileptic seizures from the 7th day of life. Examination at the age of 17 months revealed a mentally retarded boy with epileptic seizures, generalised myoclonic contractions, and abnormal ocular movements. A cerebral CT scan showed central and cortical atrophy. Lactate levels in serum, cerebrospinal fluid and urine were elevated, the pyruvate level was raised in serum. A quadriceps muscle biopsy revealed aspecific morphologic signs of a myopathy. Biochemical analysis showed decreased substrate oxidation rates in the mitochondria associated with low rates of ATP production. Total and free carnitine levels were decreased. Investigation of the respiratory chain revealed a defect in the proximal part of respiratory chain involving the region of coenzyme Q. Based on clinical and chemical data it is likely that the patient is suffering from a multi-system disorder.
Acidosis↗
Disturbed oxidative metabolism in subacute necrotizing encephalomyelopathy (Leigh syndrome).
Several disorders of oxidative metabolism have been described in association with subacute necrotizing encephalomyelopathy (SNE) or Leigh syndrome. We present an eight-year-old girl with a mild spastic paraparesis and clinical deterioration on intercurrent infections. One sib died of SNE proven by autopsy. Biochemical examination of muscle tissue points to a disturbance in the process of oxidative phosphorylation due to a disturbed oxidation of NADH. The biochemical disorders associated with SNE are reviewed. The relation of SNE to the concepts of encephalomyopathy and mitochondriopathy is discussed.
Biopsy↗
Defect of NADH dehydrogenase in Leigh syndrome.
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Brain Diseases, Metabolic↗
Differential investigation of the capacity of succinate oxidation in human skeletal muscle.
Procedures are described for the estimation of the succinate:ubiquinone oxidoreductase and succinate:phenazine methosulfate oxidoreductase activities in post-nuclear supernatants of human skeletal muscle homogenates using 2,6-dichlorophenol indophenol as the terminal electron acceptor. The influence of ionic strength and of sucrose upon these assays and upon the succinate:cytochrome c oxidoreductase activity has been investigated. Sucrose markedly interferes with the activation of the succinate dehydrogenase complex. Succinate:cytochrome c oxidoreductase activity and succinate:phenazine methosulfate oxidoreductase activity are inhibited by increasing concentrations of ions and of sucrose. Our results lead us to propose the existence of a single acceptor site for phenazine methosulfate at the succinate dehydrogenase complex, not involved in the physiological electron flux across ubiquinone. Estimation of the enzymatic activities mentioned above allows differential investigation of the functional integrity of a large part of the respiratory chain in patients suspected of suffering from a neuromuscular disorder.
2,6-Dichloroindophenol↗
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↗
Laser Doppler flowmeter measurements of skin perfusion changes associated with arterial and venous compromise in the cutaneous island flap.
Laser Doppler flowmetry (LDF) is a noninvasive, continuous measure of tissue surface microcirculatory red blood cell (RBC) flux. LDF was calibrated against varying RBC volume fractions and flow rates using extracorporeal perfusion of saphenous island flaps of dogs. The RBC flux was found to be linear with LDF signal. The difference in vascular geometry of the skin appeared to play a minor role in generating the LDF signal compared to changes in the RBC flux. In vivo experiments of varying arterial perfusion pressure, flap venous pressure, and total blood flow of the cutaneous island flap had a linear relationship with LDF signal.
Animals↗
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↗
Subacute necrotizing encephalomyelopathy (Leigh syndrome) associated with disturbed oxidation of pyruvate, malate and 2-oxoglutarate in muscle and liver.
We studied a 17-year-old girl with subacute necrotizing encephalomyelopathy (Leigh syndrome). Lactate and pyruvate levels were increased in serum and cerebrospinal fluid. The oxidation rates of all substrates tested, i.e. pyruvate in liver, and pyruvate, malate and 2-oxoglutarate in muscle, were decreased, as was the production of adenosine triphosphate plus creatine phosphate. Cytochrome content was normal. The data imply a defect in oxidative phosphorylation, outside the cytochrome region.
Adolescent↗
The reconstruction of a helical structure from projections applied to a phage tail.
A procedure has been described for 3 D-image reconstruction for helical biological structures, if more than one projection will be required to determine the contributing helical density-waves. The method was tested with a helical protein aggregate derived from a bacteriophage. The results showed the feasibility of the proposed scheme and yielded a low resolution picture (about 2.5 nm) of the protein structure.
Bacillus subtilis↗
Low-dose electron image reconstruction of negatively stained contractile phage sheath from Bacillus subtilis (PBS-Z).
The structure of the contractile sheath of the defective phage from B. subtilis (PBS-Z) has been investigated by low-dose electron microscopy and image reconstruction. The extended and contracted sheath particles were imaged by means of two negative stains which consisted of uranyl- and phosphotungstate-containing solutions of a pH of 4.2 and 7.0 respectively. Images of identical parts of the same type of specimen were recorded at a total electron dose of 80 C/m2 (5 electrons/A2) and 4 x 10(3) C/m2 (250 electrons/A2). The low-dose reconstructions of the extended and contracted sheath structure in the two stains show good correspondence and made it possible to draw the following structural conclusions. The sheath protein in both types of structure has an elongated shape, and in both structures the long molecular axis lies in a plane perpendicular to the helical sheath axis. The orientation of the protein in the extended and contracted sheath is different; the long axes differ by about 35 degrees in orientation. The reconstructions did not permit conclusions about different conformational states of the protein in both structures. These data, together with the packing parameters of the protein subunits in the contractile sheath [1], form the complete structural analysis of this biological structure by electron microscopy. The radiation damage effects which have been monitored in analyzing image pairs to the full extent may be summarized as follows. (1) Diameters of the sheath structure increase, which indicate flattening. (2) There is no loss in resolution, and layerline altitudes of the Fourier-transformed images do not change. (3) Uranyl stain behaves differently compared to phosphotungstate. In both negative stains the structural noise level increases upon irradiation as follows from the increase in phase residuals of the digital layerline data. In uranyl-stained images also more aperiodic noise appears. (4) The Fourier amplitudes of the principal layerline maxima shift towards lower spatial frequencies; phases of corresponding maxima generally remain constant. This pattern is more pronounced in the extended sheath data; there is no rationale describing these positional shifts. Moreover, in the case of contracted sheath the amplitudes of Fourier components also change more in absolute value. Therefore the damage effects also seem to depend on the type of structure embedded in the stain. (5) In the reconstructed images these radiation effects create artificial stain-excluded volumes of a type and at a radius which depend on the stain and structure.
Bacillus subtilis↗
Cavernous hemangioma of the right atrium: presumptive diagnosis by coronary angiography.
The angiographic findings in a patient with an interesting vascular tumor of the right atrium are described. The tumor was supplied by vessels from both the right and left coronary arteries and consisted of dilated blood spaces in which contrast material persisted for a prolonged period of time.
Female↗