Biomedical subjects

V Dubowitz

Publications and source records attributed to V Dubowitz.

At least 199 records · Page 11Linked to original sources

PubMed1986

Linkage studies in Duchenne and Becker muscular dystrophies.

We have studied the inheritance of four cloned DNA sequences which recognise restriction fragment length polymorphisms on the short arm of the X chromosome in families with Becker and Duchenne muscular dystrophy. We have confirmed linkage of two probe loci to the disease loci and have combined our results with those previously published to give a maximum lod score of 11.642 at a recombination fraction of 0.15 for DXS41 (probe 99.6), and a maximum lod of 15.84 at a recombination fraction of 0.15 for DXS84 (probe 754). Linkage of these diseases to the loci defined by the pERT87 probes and probe pXJ1.1 has also been studied, giving maximum lod scores of 8.634 and 5.118 at recombination fractions of 0.02 and 0.00 respectively. The information obtained using these polymorphic DNA markers, combined with pedigree and CK data, can be used to give more accurate genetic counselling to women at risk in Becker and Duchenne families.

DNA↗

PubMed1986

Responses of muscles of patients with Duchenne muscular dystrophy to chronic electrical stimulation.

The effect of chronic low frequency stimulation on the tibialis anterior muscle of children with Duchenne muscular dystrophy was investigated. Baseline data from 16 boys established low values of maximum voluntary contraction which did not improve with age. Studies of the contractile properties revealed significant slowing (p less than 0.001) of mean relaxation time compared to that of normal children's muscles. There was no loss of force during fatigue testing, as in normal children, but in contrast to normal children, there was no potentiation at lower frequencies of stimulation. Intermittent chronic low frequency stimulation of muscles in six young ambulant children with Duchenne muscular dystrophy resulted in a significant increase (p less than 0.05) in mean maximum voluntary contraction compared with the mean forces exerted by the unstimulated control muscles of the contralateral leg.

Adolescent↗

PubMed1985

Predictive value of cranial ultrasound in the newborn baby: a reappraisal.

During a 36-month period 435 babies of 34 weeks' gestation or less were regularly scanned with ultrasound. A large periventricular/intraventricular haemorrhage developed in 40 babies, and extensive cystic leucomalacia developed in 10. The neurodevelopmental outcome and the frequency of handicap in these 2 groups were compared. 9 of the 18 survivors with a large haemorrhage were found to be completely normal and only 2 showed a major handicap. However, severe cerebral palsy with mental retardation developed in all the survivors with extensive cystic leucomalacia, and 4 of the 7 babies were also cortically blind. These findings suggest that the size of the haemorrhage is not a good predictor of outcome, but that severe cystic leucomalacia is associated with a very poor prognosis.

Brain↗

PubMed1985

Increased expression of HLA ABC class I antigens by muscle fibres in Duchenne muscular dystrophy, inflammatory myopathy, and other neuromuscular disorders.

The distribution of HLA ABC class I antigens in human skeletal muscle obtained by needle biopsy was investigated by means of a monoclonal antibody (W6/32) and an immunoperoxidase technique. Five samples from normal individuals and twenty-nine from patients with various neuromuscular disorders were examined. Normal muscle fibres and those from patients with congenital muscular dystrophy expressed little or no class I antigens, whereas muscle fibres of patients with myositis and various X-linked muscular dystrophies showed consistently strong expression. In other neuromuscular diseases expression was more variable. The presence of class I antigens on diseased muscle fibres may render them susceptible to cytotoxic T cells; these antigens may thus have an important role in the destruction of muscle fibres.

Adolescent↗

PubMed1985

Diagnostic advantage of needle muscle biopsy and ultrasound imaging in the detection of focal pathology in a girl with limb girdle dystrophy.

Ultrasound imaging of the thigh in a 6-year-old girl with limb girdle muscular dystrophy showed striking focal involvement of the vastus intermedius and vastus lateralis muscles, with sparing and hypertrophy of the rectus femoris muscle. This was confirmed on needle muscle biopsy, using the Bergstrom needle, which showed normal histology in the rectus femoris and severe dystrophic change in the vastus intermedius. In neuromuscular disease, it is important to be aware of the possibility of focal muscle involvement, which can be screened for by ultrasound imaging and more effectively investigated by needle than by open muscle biopsy.

Biopsy, Needle↗

PubMed1985

Lectin binding in human skeletal muscle: a comparison of 15 different lectins.

Fifteen lectin-horseradish peroxidase conjugates have been used in a comprehensive histochemical study of human skeletal muscle. The staining patterns of many lectins were found to be coincident with the known distributions of types I, III, IV and V collagen, fibronectin and laminin. One lectin, Bandeiraea simplicifolia (BSA I), selectively stained capillaries in a blood group-specific manner, the significance of which is unknown. The results show that although lectins are useful cytochemical probes for identifying tissue glycoconjugates, lectin binding is not solely determined by monosaccharide specificity as lectins which interact with the same sugars may have completely different staining patterns. Factors such as accessibility, glycan conformation and oligosaccharide sequence also affect lectin binding in tissues. For these reasons, we conclude that a comprehensive histochemical investigation of tissue glycoconjugates should employ a large number of lectins, preferably with overlapping sugar specificities.

Histocytochemistry↗

PubMed1985

Lectin blotting of human muscle. Identification of a high molecular weight glycoprotein which is absent or altered in Duchenne muscular dystrophy.

Using a combination of sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting, a high molecular weight Ricinus communis I (RCA I)-binding glycoprotein (approx. Mr 370000) has been identified in human muscle that is consistently altered or absent in muscle from patients with Duchenne muscular dystrophy (DMD). In addition, a Mr 54000 RCA I-binding glycoprotein was identified in 4 out and 8 DMD muscle samples that was not present in normal muscle. The possibility that the Mr 370000 glycoprotein could be a muscle membrane glycoprotein which is altered or absent in DMD is discussed.

Adolescent↗

PubMed1985

Lobulated fibers in neuromuscular diseases.

Lobulated fibers have been observed in biopsies of 13 patients with various neuromuscular disorders including limb-girdle muscular dystrophy (3), distal myopathy (2), scapuloperoneal muscular dystrophy (2), congenital myopathy, Kugelberg-Welander syndrome, hypothyroidism, steroid myopathy, osteomalacia and systemic lupus erythematosus (on steroids). In all cases there were fibers characterised by small subsarcolemmal triangular aggregates or more diffuse collections extending into the interior of the muscle fiber. These were strongly reactive with oxidative enzymes, acid phosphatase, periodic acid-Schiff (PAS), Verhoeff-van Gieson (VVG) and also stained red with the Gomori trichrome technique. In 5 cases core-like fibers were also seen. Morphometric analysis of the NADH-tetrazolium reductase (NADH-TR) preparations in 11 cases showed atrophy of the lobulated fibers. Ultrastructural studies of lobulated fibers disclosed large peripheral mitochondrial aggregates and focal areas with Z-line streaming and disrupted myofibrils. We consider this structural change of the muscle fiber as a reflection of muscle cell disruption and suggest that they may progress from lobulated fibers to more atrophic core-like fibers.

Adenosine Triphosphatases↗

PubMed1985

Hearing threshold in preterm and term infants by auditory brainstem response.

Hearing thresholds were established in preterm and term newborn infants by auditory brainstem responses in the first week of life. The presence of wave V was the criterion for threshold sensitivity in infants considered neurologically optimal on the basis of stringent clinical criteria and sequential ultrasound examination. The hearing threshold was found to be at 40 dB in preterm infants between 28 and 34 weeks gestational age, at 30 dB in infants between 35 and 38 weeks, and below 20 dB in term infants. This study confirms that the thresholds of newborn infants diminish with increasing age, and there is no apparent difference whether maturation occurs inside or outside the uterus. The data should provide a baseline for objective and quantitative assessment of hearing loss early in the neonatal period.

Audiometry, Evoked Response↗

PubMed1985

Congenital centronuclear (myotubular) myopathy. A clinical, pathological and genetic study in eight children.

Eight unrelated children with centronuclear (myotubular) myopathy are described, ranging in age at the time of diagnosis from 5 days to 12 years. Six had an intrauterine onset and 5 were severely asphyxiated at birth. All had facial involvement and 6 had ophthalmoplegia. Detailed study of the parents in 7 of the families suggested an autosomal recessive inheritance or sporadic occurrence in 2 and X-linked inheritance in 5. Classification in this very variable disorder should be based on severity and mode of presentation together with the genetic pattern, allowing three subgroups to be defined: a severe neonatal X-linked recessive type, a less severe infantile or juvenile autosomal recessive type and a milder autosomal dominant type. For genetic counselling, available relatives should be examined for mild degrees of clinical involvement and morphological abnormalities on needle muscle biopsy.

Cell Nucleus↗

PubMed1985

Prolongation of walking in Duchenne muscular dystrophy with lightweight orthoses: review of 57 cases.

Fifty-seven boys with Duchenne muscular dystrophy aged between 6 years 3 months and 13 years 6 months, who were at the point of losing the ability to walk or had recently done so, were fitted with lightweight knee-ankle-foot orthoses to re-establish walking. 47 walked well and independently in their orthoses, achieving good stability and confidence. 20 are still ambulant; the other 27 stopped walking at intervals ranging from eight to 48 months. Prolongation of walking prevented the development of scoliosis, joint contractures and deformities and also benefited the boys psychologically.

Adolescent↗

PubMed1985

Chromosome 15 in Prader-Willi syndrome.

Nineteen children with the clinical features of Prader-Willi syndrome were karyotyped, using both routine Giemsa banding and high-resolution techniques. Chromosome abnormalities involving chromosome 15 were found in 10, entirely normal chromosomes in five and for the remaining four the findings were either equivocal or difficult to interpret. There was no clinical distinction between cases with and without the chromosome anomaly. Examination of three parents and a group of controls showed that the proximal end of the long arm of chromosome 15 may have a considerable degree of normal variation, which can make interpretation difficult.

Child↗

PubMed1985

Cell surface abnormality in clones of skin fibroblasts from a carrier of Duchenne muscular dystrophy.

We have previously reported that skin fibroblasts from patients with Duchenne muscular dystrophy (DMD) have a lower intercellular adhesiveness than control cells, and that cells from carriers of DMD have normal adhesiveness instead of the expected intermediate value. We have now cloned skin fibroblasts from a carrier of DMD (subject AS) who is also heterozygous for G6PD B/G6PD Mediterranean and determined the intercellular adhesiveness and G6PD phenotypes of the clones. G6PD activity was determined using the 2d-G6P/G6P ratio method. Normal cells had a percentage utilisation of 7.31% and uncloned cells from AS a value of 25.16%. Of 16 clones, 15 had normal values (mean 8.72%) while one clone was G6PD Med with a value of 57.5%. Mean intercellular adhesiveness of normal and uncloned cells from AS were 2.95 and 2.90 respectively. Of 11 clones tested, nine had normal values of adhesiveness (mean 3.1) and all these clones were G6PD B. The single G6PD Med clone had a value of 0.88, compared with 1.39 for DMD cells. We have no explanation at present for the single clone that was G6PD B but DMD-like on aggregation.

Adhesiveness↗

PubMed1985

Effects of chronic low frequency electrical stimulation on normal human tibialis anterior muscle.

The loss of force that occurred during intermittent electrically evoked tetanic contractions was determined for the tibialis anterior muscle of normal subjects. Adult muscles showed a characteristic reduction of tension over the first two to three minutes until a steady plateau was reached. Muscles of young children showed no comparable decrease of the initial tension in response to this method of fatigue testing. After fatigue the muscles of both groups of subjects produced a higher proportion of tension at lower rates of stimulation. Following prolonged chronic low frequency stimulation at 8-10 Hz, adult muscles showed a significant increase (p less than 0.01) in fatigue resistance compared to unstimulated control: the muscles of the normal child showed no measured change. It is concluded that it is possible to alter the properties of adult human muscle by superimposed low frequency electrical stimulation.

Adolescent↗

PubMed1985

A novel procedure for pattern analysis of features present on freeze-fractured plasma membranes.

We have used statistical methods for the analysis of two-dimensional point patterns to derive quantitative descriptions of the distributions of caveolae on freeze-fractured muscle fibre membranes. One method was based on a quadrat analysis while the second was a new procedure that we have called the interpoint distance analysis. We show that the latter analysis can unambiguously distinguish random, clustered and dispersed patterns and that a single parameter can be derived that can be used to compare different distributions. It is readily applicable to patterns containing several hundred points. Practical details of the method are given and a simple algorithm that can be implemented on a microcomputer is provided. The interpoint distance analysis should prove generally useful in situations where the two-dimensional distribution of objects has to be quantified.

Cell Membrane↗

PubMed1985

Duchenne muscular dystrophy: studies of cell motility in vitro.

Duchenne muscular dystrophy (DMD) is a severe degenerative disorder of skeletal muscle. It has been suggested that an abnormality of the plasma membrane may be responsible for the pathogenesis of DMD, and a number of cell surface changes have been described in DMD muscle fibres and other cell types. Alterations in cell-to-cell and cell-to-substratum adhesiveness have been reported for DMD cells and we have determined whether these alterations in cell adhesiveness affect migration of cells from DMD muscle explants. DMD cells move more rapidly and spend less time at rest than do normal or DMD carrier cells, although the differences were statistically significant only for the latter cells. An inverse relationship between cell speed and contact with surrounding cells was not observed. All cells tended to persist in their direction of movement, and there were no differences between the types of cells studied. Our results support the view that there may be a cell surface defect in DMD.

Cell Adhesion↗

PubMed1984

Altered binding of Ricinus communis I lectin by muscle membranes in Duchenne muscular dystrophy.

Recently, it has become clear that a structural or functional abnormality of the plasma membrane may be involved in the pathogenesis of Duchenne muscular dystrophy (DMD). We have used a D-galactose specific lectin, that binds strongly to the muscle cell surface, to search for differences in sarcolemmal staining in biopsies from 5 normal and 7 DMD individuals. Electron optical studies revealed a dramatic and consistent decrease in lectin binding by the muscle plasma membrane in DMD. Although unable at this stage to identify the specific molecular abnormality responsible for this decreased staining, the results provide good evidence that a basic structural change within the plasma membrane may be intimately associated with DMD.

Adolescent↗

PubMed1984

Binding of Ricinus communis I lectin to the muscle cell plasma membrane in diseased muscle.

Using an electron histochemical technique, we have observed the binding of a D-galactose-specific lectin to the muscle cell plasma membrane in muscle biopsies taken from patients with various neuromuscular disorders. In spinal muscular atrophy, the only neurogenic disease studied, the plasma membrane stained as in normal muscle. However, in the myopathies Becker and limb-girdle muscular dystrophy and in the polymyositis there was a reduction in both the occurrence and the intensity of staining of the plasma membrane. Reduced lectin binding by the plasma membrane probably reflects secondary changes in the composition of glycoproteins and/or glycolipids in the membrane and seems to be common to all these myopathies to varying degrees.

Adolescent↗