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Biomedical subjects

A M Stadhouders

Publications and source records attributed to A M Stadhouders.

At least 19 recordsLinked to original sources
PubMed1995

Immunophenotyping of congenital myopathies: disorganization of sarcomeric, cytoskeletal and extracellular matrix proteins.

We have studied the expression and distribution patterns of the intermediate filament proteins desmin and vimentin, the sarcomere components titin, nebulin and myosin, the basement membrane constituents collagen type IV and laminin, and the reticular layer component collagen type VI in skeletal muscle of patients with "classic" congenital myopathies (CM), using indirect immunofluorescence assays. In all biopsy specimens obtained from patients with central core disease (CCD), nemaline myopathy (NM), X-linked myotubular myopathy (XLMTM) and centronuclear myopathy (CNM), disease-specific desmin disturbances were observed. Vimentin was present in immature fibres in severe neonatal NM, and as sarcoplasmic aggregates in one case of CNM, while the amounts of vimentin and embryonic myosin, observed in XLMTM, decreased with age of the patients. Abnormal expression of myosin isoforms was found in several CM biopsies, although the organization of myosin and other sarcomere components was rarely disturbed. Basement membrane and reticular layer proteins were often prominently increased in severe cases of CM. We conclude that (i) desmin is a marker for individual types of CM and might be used for diagnostic purposes; (ii) the expression patterns of the differentiation markers desmin, vimentin and embryonic myosin in XLMTM, point either to a postnatal muscle fibre maturation or to a variable time-point of maturational arrest in individual patients; (iii) the correlation between the distribution patterns of extracellular matrix proteins and clinical presentation points to a role of these proteins in pathophysiology of CM.

Adolescent↗
PubMed1995

Abnormal expression of intermediate filament proteins in X-linked myotubular myopathy is not reproduced in vitro.

Expression patterns of the intermediate filament proteins (IFPs) desmin and vimentin, in biopsy material taken from a 1 day old boy with fatal neonatal X-linked myotubular myopathy (XLMTM) were compared with the expression of these proteins in cultured myotubes, from the same patient. Immunohistochemical studies revealed the persistence of high levels of desmin in virtually all, and vimentin in most, of the myofibres within the patient's biopsy. Analysis of intermediate filament expression in differentiating, cultured muscle cells did not reveal overt differences between XLMTM cultures and cultures of control muscle. Titin distribution patterns indicated a normal process of myofibrillogenesis in XLMTM myotubes. We conclude that the failure to properly regulate IFP-expression is not intrinsic to XLMTM muscle fibres. The possibility that this failure is due to a defective external, possibly neural factor, is discussed.

Cells, Cultured↗
PubMed1995

Rimmed basophilic vacuoles and filamentous inclusions in neuromuscular disorders.

To study the incidence of rimmed basophilic vacuoles (RBV) and 15-21 nm filamentous inclusions in neuromuscular disorders, other than inclusion body myositis (IBM) and to determine the diagnostic value of RBV quantitation in the differential diagnosis of IBM, we reviewed 1600 muscle biopsies for RBV and 750 biopsies for filamentous inclusions. The number of RBV-positive fibers per 10 mm2--the RBV-fiber density--was determined. The incidence of RBV in non-IBM biopsies was 8.8 per 1000. Major diagnostic categories were neurogenic disorders (n = 7) and limb girdle muscular dystrophies (LGMD) (n = 3). In IBM (n = 7) the RBV-fiber density ranged from 10.4 to 63.1 and was significantly higher than in neurogenic disorders (0.9-4.4) and LGMD (1.1-2.7). The highest value was found in rigid spine syndrome (205.8). Filamentous inclusions were seen in 2.7 per 1000 non-IBM biopsies, including familial oculopharyngeal muscular dystrophy with distal myopathy (OPMD-DM), rigid spine syndrome, acid maltase deficiency and amyloid neuropathy. RBV and filamentous inclusions coexisted in rigid spine syndrome and in familial OPMD-DM. RBV, as well as filamentous inclusions, has a very low incidence in non-IBM neuromuscular disorders; the RBV-fiber density may help to discriminate neurogenic disorders and LGMD from IBM.

Adolescent↗
PubMed1992

Differentiation of human skeletal muscle cells in culture: maturation as indicated by titin and desmin striation.

This report describes a phenotyping study of differentiating human skeletal muscle cells in tissue culture. Satellite cells (adult myoblasts), isolated from biopsy material, showed a proliferative behaviour in high-nutrition medium, but fused to form myotubes when grown in low-nutrition medium. The expression and structural organization of the intermediate filament proteins desmin and vimentin as well as the sarcomeric constituents alpha-actin, alpha-actinin, nebulin, myosin and especially titin during myofibrillogenesis in vitro, were studied by means of indirect immunofluorescence assays. The proliferating myoblasts contained both desmin and vimentin, alpha-actinin and the filamentous form of actin. Shortly after the change of medium, expression of titin, sarcomeric myosin and skeletal muscle alpha-actin was found in mononuclear cells in a diffuse, filamentous (titin, myosin, alpha-actin) or punctate (titin, myosin) pattern. Four to 10 days after the medium change, mature myotubes showed desmin, titin, alpha-actinin, nebulin, sarcomeric myosin and actin cross-striations, while vimentin was no longer detected. We conclude that human skeletal muscle cell cultures are an appropriate model system to study the molecular basis of myofibrillogenesis. Especially the presence of desmin in a striated fashion points to a high degree of maturation of the muscle cell cultures.

Actinin↗
PubMed1992

Changes in volume densities and distribution of mitochondria in rat skeletal muscle after chronic hypoxia.

In order to test the hypothesis that subsarcolemmal aggregation of skeletal muscle mitochondria, as noted in some patients with mitochondrial myopathies, is caused by an impaired oxygen supply to mitochondria, we exposed two groups of rats to 8% O2 during 44 or 45 days. One group performed mild exercise, as did a normoxic control group. After hypoxia we investigated fibre type composition, fibre diameter and capillarity of soleus and extensor digitorum longus (e.d.l.) muscles. Mitochondrial volume densities were determined by morphometric analysis. In both e.d.l. and soleus muscle fibre type composition was unchanged and fibre diameter was reduced after hypoxia. Capillary network was unchanged, hence capillary density was increased in both muscles after hypoxia (P less than 0.05 in untrained soleus). Total mitochondrial volume density was increased in soleus muscle, which was due to an increase in the volume density of intermyofibrillar mitochondria (P less than 0.05 in the trained group), whereas the volume density of subsarcolemmal mitochondria decreased. In e.d.l. muscle the volume density of both intermyofibrillar and subsarcolemmal mitochondria decreased. We conclude that subsarcolemmal aggregation of mitochondria did not occur after chronic hypoxia. In soleus and e.d.l. muscle, different changes in the volume densities of mitochondria occurred. This may be related to the relative amounts of type I and type II fibres within these muscles.

Animals↗
PubMed1991

Successful treatment of pure myopathy, associated with complex I deficiency, with riboflavin and carnitine.

We describe a 6-year-old boy who presented with progressive muscle weakness. Additional investigations revealed the existence of a myopathy and a pure motor neuropathy. Biochemical studies in muscle tissue showed a defect of NADH dehydrogenase (complex I). The patient dramatically improved on treatment with riboflavin and L-carnitine. Seven months after the start of the treatment, complex I activity was determined again and appeared to be normalized. Normalization of the enzymatic defect at this level has not been reported before. We provide a survey of nine patients with pure myopathy, associated with complex I deficiency and onset of symptoms in childhood.

Biopsy↗
PubMed1991

Increased volume density of peripheral mitochondria in skeletal muscle of children with exercise intolerance.

Muscle biopsies from 17 children with exercise intolerance and other miscellaneous symptoms and signs showed changes in mitochondrial content. The patients could not be classified according to known criteria. The histopathological changes were quantified by morphometric analysis and the clinical data were statistically analysed to detect intercorrelations. After a mean follow up period of 6.8 years (range 0.5-13.6), patients were re-examined and the course of the disease was determined. No clinical entity could be established. None of the patients showed aggravation of the exercise intolerance, but 71% noted no improvement. An increased volume density of peripheral mitochondria was shown in 59%. Based on clinical history, histopathological changes and course we suggest that some of these patients suffer from a yet unknown disturbance in energy metabolism. Recognition of these patients is important for appropriate counselling.

Adolescent↗
PubMed1991

Vimentin and desmin expression in degenerating and regenerating dystrophic murine muscles.

The distribution of the intermediate filament proteins (IFP) desmin and vimentin was studied in gastrocnemius, plantaris and soleus muscles of the dystrophic mouse strain ReJ 129 during postnatal development. Special attention was paid to the overall morphological changes in the distribution of these cytoskeletal constituents in degenerating and regenerating muscle fibres. In contrast to their normal counterparts, the dystrophic mice (ReJ 129 dy/dy) appeared to develop four types of distinct muscle fibres with immunohistochemically detectable aberrant IFP patterns. The distribution of desmin IFP differed in the dystrophic muscle fibres as compared to the normal fibres in that juxtanuclear aggregates of IFP were frequently seen. In contrast to the recent literature we conclude that these cells are regenerated myofibres exhibiting defective nuclear migration.

Age Factors↗
PubMed1991

In vitro contraction test for malignant hyperthermia in patients with unexplained recurrent rhabdomyolysis.

A few cases of non-anaesthetic-induced rhabdomyolysis in humans, predisposed to malignant hyperthermia (MH), have been described in literature. We studied a group of 6 consecutive patients with unexplained and recurrent attacks of rhabdomyolysis with the test used to determine susceptibility to MH, the in vitro contraction test (IVCT). The results of the IVCT showed 5 of these 6 patients to be MH susceptible. In cultured muscle cells from one of these patients a disturbed calcium homeostasis could be demonstrated. The relation between MH and recurrent rhabdomyolysis is discussed.

Adult↗
PubMed1991

Postnatal centralization of muscle fibre nuclei in centronuclear myopathy.

Postnatal centralization of muscle fibre nuclei, which were previously located subsarcolemmally, is described in a case of centronuclear myopathy (CNM) in a male patient with generalized muscle weakness since birth. A muscle biopsy was taken at the age of 11 months; no particular abnormalities were observed at this stage apart from an unusual variation in fibre size. A distinctly below average muscle fibre diameter, increased endomysial connective tissue, and features typical for CNM were found in a biopsy taken 9 yr later. Immunohistochemical studies using antibodies to desmin, vimentin, laminin and type IV collagen revealed altered staining patterns compared with normal fibres. The abnormalities in the patterns of cytoskeletal proteins point to a defective regulation of the composition and organization of the cytoskeletal network during development, paralleled by abnormalities in the extracellular matrix.

Cell Nucleus↗
PubMed1990

Differences in the intestinal microflora of normal and dystrophic BIO 8262 Nij Syrian hamsters.

The microflora of the gastro-intestinal tract of dystrophic BIO 8262 Nij Syrian hamsters and Kun:Sh Syrian hamsters as controls was investigated by means of culturing techniques and scanning electron microscopy. The oesophagus, forestomach, stomach, small intestine, coecum and faeces were assessed for the presence of Enterobacteriaceae, Staphylococci, Lactobacilli, Streptococci, Clostridia, Bacteroides and yeasts. The normal hamsters showed low levels of yeasts in the oesophagus, forestomach and stomach; yeasts were not present in the other compartments. Relatively low levels of Staphylococci and Enterobacteriaceae were found in all gut segments; also Bacteroides was found in low levels in the upper part of the gut. The other groups of bacteria showed relatively high levels in all segments. In dystrophic BIO 8262 Nij hamsters no Enterobacteriaceae and yeasts have been detected in the gut. Scanning electron microscopy showed no difference in adhesion between both hamsters strains.

Animals↗
PubMed1989

Fatal neonatal cardiomyopathy associated with cataract and mitochondrial myopathy.

Three patients suffering from the neonatal form of a syndrome characterized by congenital cataract, hypertrophic cardiomyopathy, and mitochondrial myopathy are described. The patients died at 7, 10 and 18 days, respectively from cardiorespiratory failure. Mitochondrial abnormalities were observed in the heart and skeletal muscle. Despite the presence of a severe lactic acidaemia pointing to a disturbed pyruvate oxidation rate in vivo, a normal pyruvate oxidation rate was demonstrated in skeletal muscle homogenates. The activities of several enzymes of the mitochondrial respiratory chain appeared to be normal, indicating an intact respiratory chain. A myoglobinopenia could be excluded. The activities of some mitochondrial enzymes and the concentration of myoglobin increase with age.

Autopsy↗
PubMed1989

[Mitochondrial defects].

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.

Adenosine Triphosphate↗
PubMed1989

Intestinal "normalization" of germ-free rabbits with rabbit caecal microflora: effect of dosing regimens.

Hysterectomy-derived germ-free (GF) rabbits were given strictly anaerobic microflora obtained from the caecum of an antibiotic-decontaminated conventional rabbit. One group was given the caecal flora diluted in doe's milk. The second group received caecal flora without doe's milk and administration of the flora was repeated when the animals were given pelleted diet. Body weight and intestinal parameters determined in the two groups of rabbits were compared with values in rabbits conventionally raised with the doe. In GF rabbits given caecal flora, the values for most intestinal parameters were similar to values recorded in conventional animals. However colonization resistance to Escherichia coli was limited in GF rabbits given caecal flora diluted in doe's milk and severely impaired in GF rabbits given caecal flora without doe's milk, although relative caecal weight was normal. It is concluded that enteric microfloras should be preferably incorporated in doe's milk when dosed to GF rabbits to obtain acceptable gastrointestinal "normalization".

Animals↗
PubMed1988

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↗