Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “DMD”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,045 records · Page 58Linked to original sources
PubMed1990

Effects of intramembrane particle aggregation on erythrocyte membrane fluidity: an electron spin resonance study in normal and in dystrophic subjects.

Mobilization and aggregation of intramembrane particles (IMPs) are physiological events observed in various cells. In erythrocyte membranes, aggregation of IMPs can be induced by the exposure of partially desprectrinized erythrocyte membranes to acidic pH. We investigated the association between IMPs aggregation, protein mobility, and membrane fluidity in erythrocyte membranes of healthy controls and Duchenne muscular dystrophy (DMD) patients by using electron spin resonance and specific spin labels for membrane proteins and lipids. In erythrocyte membranes of control subjects, the partial spectrin removal induced a decreased segmental motion of protein spin label indicating an increase of protein-protein interactions. Stearic acid spin labels 5- and 16-(N-oxyl-4,4'-dimethyloxazolidine) showed that the treatment induces an increase of membrane fluidity. In DMD patients, both treated and untreated erythrocyte membranes showed changes of membrane fluidity when compared to those of the controls. Our results suggest that defects in the interactions between skeletal proteins and/or between membrane and skeleton components may contribute to the alterations of erythrocyte membranes in DMD.

Electron Spin Resonance Spectroscopy↗
PubMed1987

Nebulin and titin expression in Duchenne muscular dystrophy appears normal.

Monoclonal antibodies which recognize different epitopes on either titin or nebulin show normal staining patterns on frozen sections of three muscle biopsies of Duchenne muscular dystrophy (DMD). Gel electrophoresis and immunoblotting performed on two of these muscle biopsies show the normal pattern of titin and nebulin polypeptides. Since the donor of one of these biopsies has a large deletion of the 5'-region of the DMD gene, our results argue against the recent proposal that nebulin is the gene mutated in DMD.

Antibodies, Monoclonal↗
PubMed1993

Detection of Duchenne muscular dystrophy gene products in amniotic fluid and chorionic villus sampling cells.

We have examined the expression of several Duchenne muscular dystrophy (DMD) gene products in amniotic fluid (AF) and chorionic villus sampling (CVS) cells. Variable amounts of dystrophin could be detected in most CVS and AF samples by immunoprecipitation followed by Western blot analysis. PCR analysis demonstrated the presence of the muscle type dystrophin mRNA in all AF cell cultures. The brain type dystrophin mRNA was also detected in some of these cultures. These DMD gene transcripts are of fetal origin and are produced by most or all clonable AF cells. The results may facilitate the development of a method for prenatal diagnosis of DMD, based on the expression of the gene in AF and CVS cells.

Amniotic Fluid↗
PubMed1992

A 10-year follow-up study by orthogonal Frank lead ECG on patients with progressive muscular dystrophy of the Duchenne type.

A 10-year follow-up study by orthogonal Frank lead electrocardiography was performed on 25 patients with progressive muscular dystrophy of the Duchenne type (DMD). With advancing age, no apparent changes were observed in the duration and amplitude of the P wave or in the PR interval, whereas the duration of the QRS complex tended to increase. The amplitudes of the R wave in lead X (Rx) and lead Y (Ry) tended to decrease from 1.75 +/- 0.90 and 1.96 +/- 0.59 mV to 0.80 +/- 0.63 and 1.39 +/- 0.62 mV (p < 0.01), whereas the amplitude of the S wave in lead X tended to increase from 0.24 +/- 0.23 mV to 0.53 +/- 0.36 mV in 10 years after initiation of the study (p < 0.01). It is noteworthy that the Ry amplitude began to decrease markedly from the seventh year after the initiation of this study, whereas the Rx amplitude showed a gradual and unceasing decline through the 10-year period. Observation of the sequential changes of the QRS loops in three planes clearly demonstrated that the electrical force tended to decrease in the leftward and inferior directions and increase in the rightward direction. It is of interest that the frequency of occurrence of the deep Q wave was found to be quite high even in the early stages of DMD and that it did not display a direct relation to the sequential evolution of this disease. It can be concluded that observation of the sequential changes in the QRS complex allows estimation of the extent and direction of myocardial involvement in DMD.

Adolescent↗
PubMed1981

Manifesting carrier of x-linked Duchenne muscular dystrophy.

The authors have investigated the uncommon occurrence of a boy affected with Duchenne muscular dystrophy (DMD) whose mother showed myopathic features in the clinical history, EMG, biochemical tests and muscle biopsy. This study suggests that the patient's mother is a manifesting carrier of X-linked DMD with clinical, neurophysiological, biochemical and histological findings of X-linked DMD with an almost complete inactivation of the paternal X-chromosome (lyonization).

Adolescent↗
PubMed1983

Response to ionising radiation in Duchenne muscular dystrophy.

Using lymphoblastoid cell cultures the response to gamma (gamma)-radiation, was examined in 6 Duchenne muscular dystrophy (DMD) patients; 2 clinically normal males as negative controls, and 2 patients with ataxia telangiectasia (AT) showing sensitivity to ionising radiation as positive controls. In a series of experiments, cell recovery and growth at day 2 post radiation, was determined after 5 separate gamma-irradiation dose levels: 50, 100, 150, 200 and 300 rads. The DMD cell strains showed a radiation dose response that was significantly greater than in cells from 2 normal males, while both DMD and normal cells were significantly less responsive than were AT-sensitive cell strains.

Adolescent↗
PubMed1983

Thermodynamic behaviour of membrane enzymes in Duchenne muscular dystrophy.

Erythrocyte ghost preparations have been prepared from blood of Duchenne patients (DMD), female carriers of the disease and controls. Arrhenius plots of Na+, K+-ATPase activity of these membrane preparations show a biphasic response for controls. For 75% of DMD and carriers the response is monophasic. This is not an inherent property of the membrane since it can vary over time in the one individual and it can be induced in normal membranes by preincubation with DMD plasma. Arrhenius plots of AChE activity showed no such difference between the three sources of blood.

Acetylcholinesterase↗
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

Serum carbonic anhydrase III in progressive muscular dystrophy.

Serum carbonic anhydrase III (CA-III) levels were determined by means of an enzyme immunoassay method and compared with serum creatine kinase (CK) and muscle-specific enolase (MSE) levels in 143 patients with four types of progressive muscular dystrophy (PMD), namely, Duchenne muscular dystrophy (DMD), limb-girdle dystrophy, facioscapulohumeral dystrophy and congenital dystrophy. Serum CA-III levels were raised in the majority of patients, especially in those with DMD. In DMD patients, the gradual decline in the CA-III level was observed with age. High correlations were found between CA-III, CK and MSE levels. The frequency of cases with elevated CA-III levels was the same as or greater than that of elevated CK or MSE levels in four types of PMD. These results suggest that serum CA-III may be a useful marker of muscle disease.

Adolescent↗
PubMed1988

Evaluation of immunoregulatory cells in Duchenne muscular dystrophy and spinal muscular atrophy among African and Indian patients.

Suppressor cells were assayed by numerical and functional tests in Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA) among African and Indian children in order to contribute to an understanding of the pathogenesis of these neurological disorders. Peripheral blood mononuclears (PBM) were classified as total T cells and T cell subsets by the OKT series of monoclonal antibodies and as B cells by the presence of surface immunoglobulin. The suppressive effects of PBM pretreated with concanavalin A (Con A) on normal homologous phytohaemagglutinin (PHA) transformation of mononuclear cells was determined. PBM stimulation by PHA was also assessed. Patients with DMD had a significant increase (P = 0.0353) in the number of T suppressor/cytotoxic cells (1218 +/- 142 cells/mm3, mean +/- SE) as compared to controls (815 +/- 95 cells/mm3) and a significant reduction (P = 0.0282) in OKT4+ cells expressed as a percentage of OKT3+, 50% +/- 3 compared to 61% +/- 3. No differences were detected in any of the numerical assays employed in SMA as compared to controls, or within SMA patients according to severity of disease. Suppressor function and PHA transformation were normal in both groups of patients. No significant correlations were detected between numerical and functional assays of suppression. The implication of the results obtained for the role of immunoregulatory cells in the pathogenesis of DMD in these children is discussed.

Adolescent↗
PubMed1989

Expression of class I and class II MHC antigens in neuromuscular diseases.

The distribution of HLA class I and class II antigens has been investigated in cryostat sections of a series of 200 skeletal muscle biopsy specimens from patients with various neuromuscular disorders. Normal muscle fibres expressed no detectable class I antigens, whereas muscle fibres of patients with inflammatory myopathies and Duchenne (DMD) and Becker (BMD) muscular dystrophy showed consistently strong expression. In other neuromuscular diseases expression of class I antigens was more variable. No expression of class I antigens was observed on muscle fibres in samples from fetuses "at risk" for DMD and BMD or from female carriers of these disorders. The immunocytochemical assessment of HLA class I antigen expression was confirmed by a quantitative radioimmunoassay which demonstrated a 3-fold increase in the level of expression in muscle samples from patients with DMD and juvenile dermatomyositis. Class II antigen expression was never observed on muscle fibres in biopsies from normal individuals or any of the neuromuscular disorders. However, these antigens were expressed by endothelial cells present in these samples. Muscle specimens from fetuses and early in postnatal life showed very limited expression of class II antigens. They were expressed at a reduced level by about 3 months of age, but strong expression of class II antigens was not observed until about 1 year of age. The mechanism of induction of class I antigen expression in diseased muscle is not known. The appearance of class I antigens on diseased muscle may make the affected tissue a target for cytotoxic T cells and may thus have a role in muscle fibre damage in inflammatory myopathies and the X-linked muscular dystrophies.

Adolescent↗
PubMed1989

Dystrophin in skeletal muscle. II. Immunoreactivity in patients with Xp21 muscular dystrophy.

In the preceding paper a sensitive Western blotting analysis system based on the use of a monoclonal antibody to dystrophin was described. Here we report the immunoreactivity on blots and on unfixed frozen sections of muscle from patients with Duchenne (DMD) and Becker (BMD) muscular dystrophy. Muscle from 3 BMD patients showed variation both in the band pattern observed on blots and in the immunocytochemical labelling of dystrophin on frozen sections. In contrast to previous reports, we were able to detect some minor dystrophin bands on blots from 6 of 9 DMD biopsy samples. Tissue sections from 8 of the 9 contained isolated fibres with dystrophin-positive labelling. We conclude that the majority of DMD patients have muscle fibres which can synthesize dystrophin in a limited manner.

Adolescent↗
PubMed1990

Changes in surface morphology and basal lamina of cultured muscle cells from Duchenne muscular dystrophy patients.

Cultured muscle cells from Duchenne muscular dystrophy (DMD) patients show altered growth from the mononucleated stage: abnormal morphology, decreased adhesiveness, reduced number of population doublings and delayed fusion. On the basis of these findings, a study was undertaken to observe cell shape and surface morphology by scanning electron microscopy and to define the immunocytochemical localization of 4 basal lamina components (type IV collagen, laminin, fibronectin, heparan sulfate proteoglycan (HSPG]. Eight DMD muscle cultures with fusion indices higher than 65% were compared to muscle cultures from 10 age-matched controls. The following results were noted for the dystrophic muscle cells: (1) the cell surface was smooth with a few slender cell processes and anchorage extensions; (2) distribution of type IV collagen and laminin was heterogenous, with large patches (type IV collagen) or a reticulum (laminin); (3) in contrast, fibronectin and HSPG levels were clearly decreased. These molecules did not form a network but rather were arranged in thick filaments and patches. Cell surface morphology may be related to the decreases in fibronectin and HSPG, which could reflect a more general decrease in basal lamina. Such findings could explain the low adhesiveness of the cells from dystrophic cultures and the delayed fusion of myoblasts. Although these abnormalities were maximally expressed after myoblast fusion, they were already present in mononucleated cells and their connection with the primary defect in DMD, i.e., lack of dystrophin, must now be clarified.

Basement Membrane↗
PubMed1991

Limb-girdle syndrome: a genetic study of 22 large Brazilian families. Comparison with X-linked Duchenne and Becker dystrophies.

The differential clinical diagnosis between the X-linked muscular dystrophies (DMD and BMD) and autosomal recessive limb-girdle muscular dystrophy (LGMD), which is extremely important for genetic counseling, may be very difficult. The aim of the present report is to describe clinical and laboratory findings in patients from large families, with AR inheritance, in an attempt to characterize better cases which have been diagnosed as LGMD compared with the X-linked forms. The main features analysed are: age of onset and of confinement to a wheelchair, reproductive performance, serum enzymes (CK and PK) and dystrophin assessment (through immunohistochemistry and Western blot). Twenty-two families, with 62 affected patients diagnosed as limb-girdle muscular dystrophy, were included in this report. In 19 families, the patients had a milder clinical course, while in the remaining 3, the progression of the disease was continuous and clinically similar to X-linked DMD ("DMD-like"). A high consanguinity rate was observed among the parents of the affected patients (77%). No major clinical difference was observed between the X-linked and the AR forms. However, muscle dystrophin was found qualitatively and quantitatively normal in the autosomal forms but absent or abnormal in the X-linked ones. The reproductive performance was significantly higher for male than female patients. In addition, a surprising finding was the significantly greater fitness estimated for male LGMD cases as compared with Becker patients of comparable age studied in our center. The implications of such findings are discussed.

Adolescent↗
PubMed1993

Abnormal localization of laminin subunits in muscular dystrophies.

To address potential involvement of muscle basal lamina and membrane cytoskeleton proteins in the etiology of non-dystrophinopathy muscular dystrophies, we examined the immunostaining intensity and distribution of laminin subunits (A, B1, B2 and M), type IV collagen, dystrophin and spectrin in skeletal muscle biopsies from 64 myopathic patients (17 Fukuyama congenital muscular dystrophy: FCMD, 13 congenital muscular dystrophy unrelated to FCMD: other CMD, 16 Duchenne muscular dystrophy: DMD, and 18 other neuromuscular diseases. In FCMD muscle, we found a significant reduction of laminin M (merosin; a striated muscle specific basal lamina-associated protein) with approximately 26% of levels seen in controls by quantitative immunofluorescence. Other CMD and DMD muscles showed less dramatic reductions (78%, 80%, respectively). The localization of laminin M was also abnormal in FCMD muscle. Laminin B1 and B2 showed abnormalities similar to those observed with laminin M, but were less marked. Laminin A was only detected in rare regenerating fibers in control biopsies, whereas it was seen around most muscle fibers in FCMD patients, and in dystrophin deficient muscle fibers from DMD patients and its carrier. Staining intensity of type IV collagen in FCMD muscle was not significantly different from the other diseases. These findings may implicate a primary or central role for the basal lamina in FCMD muscle.

Adolescent↗
PubMed1993

Cellular energetics of dystrophic muscle.

Cytosolic pH and phosphorus metabolite ratios in skeletal muscle were measured by 31P magnetic resonance spectroscopy in patients with Duchenne muscular dystrophy (DMD) and Becker's muscular dystrophy (BMD) and in Duchenne/Becker carriers. In resting dystrophin-deficient muscle, there was a decrease in phosphocreatine (PCr) and increase in orthophosphate (Pi) relative to ATP, and an increase in calculated free [ADP]. Phosphomonester and phosphodiester were also increased relative to ATP. These changes were largest in DMD, smaller in BMD and small or absent in carriers. Cytosolic pH was increased substantially in DMD, moderately in BMD and slightly but significantly in gastrocnemius of carriers. Raised intracellular pH thus appears to be the most characteristic abnormality in dystrophin-deficient muscle. Responses to erobic exercise were studied in the forearm muscle flexor digitorum superficialis of carriers. PCr depletion during exercise was greater than normal but the fall in pH was disproportionately small, resulting in increased [ADP]. This is likely to result either from reduced anaerobic glycogenolysis to lactic acid or from increased proton efflux (as is seen in mitochondrial myopathy). Detailed analysis suggests: (1) at the start of exercise, calculated lactic acid production was increased, as was the rate of PCr depletion, suggesting that there was no absolute defect of glycogenolysis. (2) At the start of recovery, calculated proton efflux was not increased, although as the pH at the end of exercise was higher than in controls and proton efflux is normally pH-dependent, an up-regulation of proton efflux cannot be excluded. (3) Recovery of PCr, Pi and ADP after exercise were not impaired, suggesting that mitochondrial function is normal.

Adenosine Diphosphate↗
PubMed1996

An in vivo and in vitro H-magnetic resonance spectroscopy study of mdx mouse brain: abnormal development or neural necrosis?

Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder primarily affecting young boys, often causing mental retardation in addition to the well-known progressive muscular weakness. Normal dystrophin expression is lacking in skeletal muscle and the central nervous system (CNS) of both DMD children and the mdx mouse model. The underlying biochemical lesion causing mental impairment in DMD is unknown. 1H-magnetic resonance spectroscopy (1H-MRS) detects choline-containing compounds, creatine and N-acetyl aspartate (NAA) in vivo. NAA is commonly used as a chemical marker for neurons, and a decline in NAA is thought to correlate with neuronal loss. Control mice were compared to mdx using a combination of in vivo and in vitro 1H-MRS methods to determine whether neural necrosis or developmental abnormalities occur in dystrophic brain. NAA levels were normal in mdx brain compared to controls suggesting minor, if any, neuronal necrosis in dystrophic brain. In contrast, choline compounds and myo-inositol levels were increased, indicative of gliosis or developmental abnormalities in dystrophic brain.

Animals↗
PubMed1991

Negative halothane-caffeine contracture test in mdx (dystrophin-deficient) mice.

The genetics of malignant hyperthermia (MH) are ill-understood; however, the association of Duchenne muscular dystrophy (DMD) with MH is well known. A deficiency of dystrophin is common to both the DMD and mdx mouse, an animal model for DMD. Using muscle contracture tests for MH, we have shown that in the mdx mouse there is no MH susceptibility, suggesting the lack of a direct role of the dystrophin in the development of MH syndrome.

Abdomen↗