[Morphological study of mitochondrial myopathies].
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Crystallization↗
Biomedical subjects
A M Stadhouders
Publications and source records attributed to A M Stadhouders.
Two types of mitochondrial crystals in diseased human skeletal muscle fibers.
Mitochondrial crystalline inclusions, frequently found in mitochondrial myopathies, were analyzed by crystallographic techniques and computer-aided image processing. It could be shown that these structures were real crystals. There are two distinct types of crystal, which can be distinguished by shape, size, and pattern. So-called type I crystals are usually present in the intracristal space, whereas the type II crystals are preferentially located in the intermembrane space between outer and inner mitochondrial membranes. The unit cell dimensions were found to be 38 x 34 x 8 nm for the type I crystals and 20 x 17 x 8 nm for the type II crystals. These results strongly suggest that the crystals are composed of macromolecules, presumably proteins. Arguments are presented that indicate that type I crystals occur only in type 1 muscle fibers and type II crystals in type 2 muscle fibers.
Adult↗
Mitochondrial myopathy with lactic acidaemia, Fanconi-De Toni-Debré syndrome and a disturbed succinate: cytochrome c oxidoreductase activity.
A patient with severe muscular hypotonia, failure to thrive, a metabolic acidosis and a renal tubular dysfunction is presented. The disease followed a fatal course. Blood lactate and pyruvate levels as well as lactate/pyruvate ratios were strongly elevated. There were a massive excretion of lactate in urine, a generalized hyperaminoaciduria, a proteinuria and a mellituria. The carnitine concentration was diminished in blood and muscle tissue. Biochemical investigations of skeletal muscle and liver tissue revealed a defect in the respiratory chain at the level of succinate: cytochrome c oxidoreductase. The defect could not be demonstrated in cultured fibroblasts.
Acidosis, Lactic↗
A mitochondrial encephalomyopathy with a partial cytochrome c oxidase deficiency of muscle.
A 16 year old girl showed delayed psychomotor development. In infancy, exercise intolerance, cerebellar signs, deteriorated with increasing intercurrent infections, and disturbances of breathing and cardiac rhythm became manifest. From the age of 7 years there was chronic progressive psychomotor deterioration, with hypotonia, a bilateral pyramidal and cerebellar syndrome, and mild epilepsy. CSF pyruvate and lactate levels were elevated, and lactate content was elevated in the urine. There was an abnormally high rise of lactate levels on moderate exercise and an abnormal response to pyruvate loading. Quadriceps muscle biopsies obtained at age 10 and 16 years showed ragged-red fibres, and a decreased cytochrome c oxidase activity and cytochrome aa3 content. Cytochrome c oxidase activity in fibroblasts was normal. Clinical signs and symptoms in association with a disturbance of mitochondrial energy metabolism led us to diagnosis of probable Leigh syndrome.
Adolescent↗
[Mitochondrial myopathies].
Mitochondrial myopathies are characterized by structural and functional abnormalities of the mitochondria. The diseases are best classified according to the underlying biochemical defect. In this article the variability of clinical expression and mitochondrial abnormalities is illustrated. An exact diagnosis is a prerequisite for a rational therapy and genetic counseling. In exceptional cases antenatal diagnosis should be possible.
Cytochrome-c Oxidase Deficiency↗
Axilla skin biopsy: a reliable test for the diagnosis of Lafora's disease.
Skin biopsies from the axilla were examined in 7 patients with clinical signs and symptoms of Lafora's disease, in 9 relatives (7 parents and 2 siblings), and in 17 patients with chronic or progressive degenerative neurological disorders and chronic epilepsy, who served as controls. In the biopsies of all patients with Lafora's disease, typical periodic acid-Schiff (PAS)-positive inclusions were present in the myoepithelial cells of the secretory acini of the apocrine glands and/or in the cells of the eccrine duct. No abnormalities were found in the biopsies from relatives and controls. We conclude that axilla skin biopsy is an easy and reliable test for diagnosing Lafora's disease, and is preferable to liver biopsy, but has no value for carrier detection.
Axilla↗
Hereditary mitochondrial hypertrophic cardiomyopathy with mitochondrial myopathy of skeletal muscle, congenital cataract and lactic acidosis.
A six day old boy died from an hereditary hypertrophic cardiomyopathy which was associated with mitochondrial myopathy of skeletal muscle, congenital cataract and lactic acidosis. In heart and skeletal muscle identical mitochondrial abnormalities were found: paucity and abnormal arrangement of cristae, formation and extrusion of vesicle-like structures and crystalline inclusions in the matrix compartment. Electron-cytochemistry revealed that only part of the mitochondria reacted positively for cytochrome oxidase activity. Morphometric analysis indicated that the cardiomegaly was due to cellular hypertrophy, which might be caused by an increase in the mitochondrial mass. The cardiac hypertrophy in this syndrome can be classified histopathologically as mitochondrial hypertrophic cardiomyopathy.
Acidosis, Lactic↗
Morphological observations in skeletal muscle from patients with a mitochondrial myopathy.
Mitochondrial metabolic dysfunction is considered to be the cause of certain congenital myopathies and a number of multisystem disorders in humans. The morphological hallmark of these diseases is the 'ragged red' fibre, which shows abnormally intensive oxidative enzyme reactions. Electron microscopy reveals that the numerically increased mitochondria in these fibres are often markedly enlarged and possess aberrant configurations of cristae. The mitochondrial matrix often contains lipid-like inclusions or shows vacuolation. The most characteristic mitochondrial abnormality is the occurrence of highly ordered inclusions in the intracristal or intermembrane space. These inclusions appear to be true crystals, composed of proteinaceous material. It is argued that the activity of accumulation of proteins in the mitochondria is related to the nuclear and nucleolar hypertrophy noticeable in the ragged red fibres. Since protein crystals in mitochondria in particular occur when an increased capillary density around the ragged red fibres is present, it is suggested that oxygen free radicals and lipid peroxidation processes are involved in the ragged red fibre pathology.
Crystallization↗
Secondary mitochondrial pathology.
A considerable number of myopathies seem to involve the mitochondria but the various causes may be situated outside the mitochondria. These can be categorized as (1) deficiency; (2) intoxication; (3) disturbed regulatory control; (4) hypoxia; (5) disturbed interaction with other cell organelles and (6) unidentified causes.
Carnitine↗
Neuromuscular investigations in retinitis pigmentosa.
Five patients with primary pigmentary dystrophy of the retina (retinitis pigmentosa) were tested on the integrity of their neuromuscular system. Clinical, electrophysiological and biochemical abnormalities were not found. A skeletal muscular biopsy was performed and histochemical, electron-microscopical and biochemical investigations were carried out. Only aspecific or minimal abnormalities were found. The mitochondrial functioning was especially explored and was found intact. Skeletal muscle examination is of no use in the study of retinitis pigmentosa.
Collagen↗
The attachment of filamentous segmented micro-organisms to the distal ileum wall of the mouse: a scanning and transmission electron microscopy study.
Scanning electron micrographs are presented of the ileal epithelium of mice aged 5, 15, 20 and 25 days. During this period the villous pattern develops to full maturity. By the twentieth day of life a segmented filamentous micro-organism colonizes the ileal epithelium and is firmly attached via a small segment. During the first days of colonization the segmented filamentous micro-organisms themselves are subcolonized by small rod-shaped bacteria, presumably lactobacilli. At the age of 25 days this subcolonization was no longer observed.
Animals↗
[Malignant hyperthermia: case-finding of subjects at risk].
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Adenosine Triphosphate↗
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↗
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↗
The use of backscattered electrons in analytical electron microscopy for the measurement of the mass of individual rat blood platelets.
The backscattered electron signal, generated in individual cells, has been used to measure the dry mass of these cells. Absolute mass values were obtained by comparing the backscattered electron signals of cells to the signals of polystyrene-latex spheres of known mass. The technique was carried out in an automated analytical scanning transmission electron microscope and applied to rat blood platelets. The resulting mass distributions agreed well with the distribution measured with a method that uses the transmitted electron signal by means of densitometric analysis of electrographs. Also the range of masses was in agreement with values deduced from data in the literature. The fully automated technique has the advantage that it is direct, fast, and that thicker specimens can be measured than is possible using the transmitted electron signal. The method is intended for use in combination with quantitative electron probe X-ray microanalysis and is then able to produce elemental mass fractions of biological specimens at the subcellular level.
Animals↗
An autosomal dominant type of congenital muscular dystrophy.
A family with an autosomal dominant type of congenital muscular dystrophy (CMD) will be reported. In general, an autosomal recessive mode of inheritance is accepted for CMD. In 1980, Kalyanaraman et al reported another family with an autosomal dominant CMD with possible involvement of the central nervous system (CNS). Our report concerns a father and daughter suffering from CMD without CNS involvement. The histological findings, especially some mitochondrial abnormalities in the muscle biopsy were remarkable.
Adult↗
Feasibility of a concanavalin A-peroxidase labeling method to detect cancerous and precancerous lesions of the uterine cervix.
For the detection of cancerous and precancerous lesions in cervical cytopathology, the feasibility of a concanavalin A-peroxidase labeling procedure was tested and compared with the Papanicolaou method. To this end, the percentage of labeled flattened epithelial cells with a morphologically normal appearance present in cervical cell suspensions was determined. It was found that the mean labeling percentage of the control group was 71% (SD, 11%). The means for mild, moderate, and severe dysplasia groups were, respectively, 54% (SD, 19%), 48% (SD, 13%), and 44% (SD, 16%). The mean for the carcinoma in situ group was 32% (SD,11%), and for the squamous cell carcinoma group 16% (SD, 5%). It appeared that the labeling percentage gradually decreases with increasing atypia of the epithelium as confirmed by histological observation. A complete dissimilarity was found between healthy individuals and cancer patients. In a follow-up study it was found that the mean labeling percentage did not alter in cases of an unchanged stage of disease. A reestablishment of the normal concanavalin A-peroxidase labeling percentage often appeared once the cancerous or precancerous lesion was treated. In conclusion, the concanavalin A-peroxidase labeling method can be considered as a supplementary technique to the Papanicolaou method for the early detection of cervical cancer. It reduces the effect of sampling and screening errors of the Papanicolaou method, and it allows a more objective cytological diagnosis. In addition, it may possess prognostic significance.
Carcinoma in Situ↗
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↗