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At least 613 records · Page 34Linked to original sources
PubMed1989

[Membrane changes in Duchenne/Becker muscular dystrophy: lectin binding and localization of dystrophin].

An RCA I-lectin binding glycoprotein of Mr = 370 kD is missing from or altered in the plasma membrane of Duchenne muscular dystrophy (DMD) skeletal muscle. In the present study the carbohydrate chain of this glycoprotein was localized to the external face of the plasma membrane in human skeletal muscle, and dystrophin, the protein product of the DMD gene, was localized to the inner (cytoplasmic) face. On double labelled Western blots the two proteins appeared as closely apposed but distinctly separate bands. Comparison of the plasma membrane binding of five lectins with overlapping sugar specificities in skeletal muscle from patients with DMD and the allelic milder disease form, Becker muscular dystrophy (BMD) showed that the RCA I-binding glycoprotein also strongly binds to phytohaemagglutinin, thereby largely characterising the carbohydrate binding site. This glycoprotein was absent or altered in DMD and markedly reduced in clinically manifest BMD but present in preclinical clinical BMD. There was no general depletion of plasma membrane glycoproteins in DMD because consistent plasma membrane binding could be demonstrated by peanut and maclura pomifera lectin. The possible implications of these findings for the pathogenesis of DMD/BMD are discussed.

Adolescent↗
PubMed1989

Dystrophin analysis in clonal myoblasts derived from a Duchenne muscular dystrophy carrier.

Clonal myogenic cell cultures were established from a potential heterozygote for a mutant Duchenne muscular dystrophy (DMD) gene who was also heterozygous for isozymes of the X-linked enzyme glucose-6-phosphate dehydrogenase. Previous tissue culture studies of this muscle donor demonstrated equal proliferative capacity of myoblasts that had lyonized either the paternal or maternal X-chromosome, indicating that mutation of the DMD gene does not affect growth of myoblasts. If this muscle donor were a gonadal mosaic, this conclusion would be incorrect. In the present study, only those myogenic colonies expressing the glucose-6-phosphate dehydrogenase-A isozyme were found to express dystrophin, indicating that this woman was indeed a heterozygote for DMD. By documenting dystrophin deficiency in a specific population of myogenic cells from this woman, we verify our previous conclusion regarding the normal proliferative capacity of DMD myoblasts. Somatic cell testing of dystrophin expression may offer an alternative to established genetic carrier tests for those women in whom deletions of the DMD are not detectable, whose pedigree structure does not permit linkage analysis, or in whom standard phenotypic analyses are ambiguous.

Blotting, Western↗
PubMed1987

Familial inheritance of a DXS164 deletion mutation from a heterozygous female.

Restriction-fragment-length-polymorphism analysis was used to examine a female who is segregating for Duchenne muscular dystrophy (DMD) and a deletion of the DXS164 region of the X chromosome. The segregating female has no prior family history of DMD, and she has two copies of the DXS164 region in her peripheral blood lymphocytes. The following two hypotheses are proposed to explain the coincidence of the DMD phenotype and deletion of the DXS164 region in her offspring: (1) she may be a gonadal mosaic for cells with two normal X chromosomes and cells with one normal X chromosome and an X chromosome with a deletion of the DXS164 region; and (2) she may carry a familial X;autosome translocation in which the DXS164 region is deleted from one X chromosome and translocated to an autosome. The segregation of DMD and the DXS164 deletion in this family illustrates the importance of extended pedigree analysis when DXS164 deletions are used to identify female carriers of the DMD gene.

Chromosome Deletion↗
PubMed1987

Expression of the Duchenne's muscular dystrophy gene in cultured muscle cells.

A partial cDNA clone for the Duchenne's muscular dystrophy (DMD) locus was used to investigate the expression of this locus in human muscle in vitro. Hybridization to a 14-kilobase RNA transcript was demonstrated in both fetal and mature human skeletal muscle and four lines of human muscle cells in culture. The DMD transcript was not detected in cultured cells outside the muscle lineage. In cultured muscle cells, gene expression was evident only in myotubes both before and after innervation with mouse spinal cord. Primary cultures of human myoblasts did not show the presence of the DMD transcript prior to fusion to form myotubes. An in vitro model is potentially an excellent system in which to investigate factors controlling expression of the DMD gene in normal muscle and how this expression is altered in cultured DMD muscle.

Animals↗
PubMed1986

[Cardiac manifestation of progressive muscular dystrophy of the Duchenne type].

Autopsy studies have shown that cardiomyopathy of Duchenne's muscular dystrophy (DMD) is characterized by fibrosis of the posterobasal and contiguous lateral wall of the left ventricle. This study was designed to determine whether stress testing would improve the sensitivity of echocardiography to detect secondary impairment of regional myocardial function. 12 patients aged 5 to 23 years with DMD were investigated. TM- and 2D-echocardiograms were performed before and during graded infusion of angiotensin (A) (0.5 to 5.0 mcg/min), and parameters of cardiac function analyzed. Satisfactory echocardiograms were obtained in all patients. Stress testing with A proved feasible in DMD and did not interfere with echocardiography. Before A all patients were in regular sinus rhythm and free of cardiac symptoms. Left ventricular function was normal in 9 patients and considered abnormal in 3 patients with hypokinesis and increased echo intensity of the posterobasal and lateral wall (2D short axis view) and/or a posterior wall to septal amplitude ratio of less than or equal to 1.1 (TM-echocardiogram). During A mean blood pressure rose and heart rate dropped significantly. 9 patients had marked supraventricular arrhythmias, 8 complained of dyspnea, cough or chest pain. Hypo- or akinesis of the posterobasal and sometimes the lateral wall was seen in 8, and a posterior wall to septal amplitude ratio of less than or equal to 1.1 in 9 patients. 3 patients, all with a muscle score of 60% or higher, remained free of symptoms and had no regional contraction abnormalities. Thus, clinical symptoms during A suggested latent congestive heart failure in many of the patients, and echocardiography identified provokable contraction abnormalities of such segments of the ventricular wall known to be most frequently involved in the dystrophic process in DMD. Stress testing revealed a correlation between clinical symptoms, abnormal echocardiographic findings and extent of the skeletal muscle disease in our study group. Physical limitation seems to protect the heart against demands that would otherwise cause earlier clinical manifestation of the cardiomyopathy in DMD.

Adolescent↗
PubMedDate not supplied

[The respiratory function in muscular dystrophies (author's transl)].

The principal cause of death in Duchenne muscular dystrophy (DMD) results from a respiratory involvement, classically defined as a restrictive syndrome. The respiratory function in muscular dystrophies (MD) was studied using spirometer respiratory function tests on 190 patients, classified into five distinct groups, according to accurate clinical and genetic findings. The three adult types of MD (Becker type, limb girdle type, facio-scapulo-humeral type) are characterized by pulmonary function approaching normal. DMD is always characterized by a restrictive syndrome. A high significant difference between adult and DMD types is confirmed by statistical analysis. In DMD, vital risks are variable according to variations of the level of absolute value of vital capacity. It is useful to distinguish three types in DMD: major involvement or type I, severe involvement or type II, moderate or mild involvement or type III.

Adolescent↗
PubMedDate not supplied

Formation of a beta-glucuronidase-resistant glucuronide conjugate of digitoxin by dog liver microsomes.

The aim of these studies was to characterize the glucuronide conjugates of digitoxin and digitoxigenin monodigitoxoside (DMD) produced by liver microsomes from the dog with respect to hydrolysis by beta-glucuronidase and to behavior on HPLC. These results have been compared with studies of conjugates produced by liver microsomes from the rat. Glucuronidation was similar with both substrates with dog microsomes, whereas rat microsomes formed the glucuronide with DMD but not with digitoxin. The DMD glucuronide from both species was completely hydrolyzed by beta-glucuronidase, but no hydrolysis of digitoxin glucuronide was detected. The digitoxin glucuronide was hydrolyzed by a buffer at pH 1.5 but not at pH 10. After acid hydrolysis, the major products appear to be digitoxigenin and DMD glucuronide. These results suggest that glucuronidation of certain drugs by the dog is quite different from that of other species and that the dog may be the only species that possesses a glucuronosyltransferase capable of forming a glucuronide conjugate with digitoxin. The dog also has a glucuronosyltransferase, similar to that in the rat, which is responsible for glucuronidation of DMD. Whether this represents a single glucuronosyltransferase or two different enzymes remains to be elucidated.

Animals↗
PubMed1994

[Ultrastructural observations on 24 cases of pseudo-hypertrophic muscular dystrophy].

Muscular biopsy specimens of 24 cases of pseudo-hypertrophic (Duchenne's) muscular dystrophy (DMD) were studied with light and electron microscopy. Ultrastructural changes include: I. Disappearance of sarcolemma in focal areas of muscle fibers with degeneration or focal necrosis, which may be the preliminary muscle fiber changes in DMD. 2. Repair of sarcolemma and regenerative sarcomere were observed in some injured muscle fibers, but the ability to repair and regeneration being so weak that injured muscle fibers can not be completely restored. 3. In the early stage of DMD when muscle fibers have not yet to become obviously atrophied, fat cell infiltration between swollen or intact muscle fibers can be observed but cannot be explained. In addition, 3 carriers (mothers of 3 DMD patients) and one asymptomatic brother of a DMD patient were examined, some serological and ultrastructural changes were found.

Child↗
PubMed1993

The incidence of Duchenne muscular dystrophy in eastern Austria. The controversy regarding CK screening.

The incidence of Duchenne muscular dystrophy (DMD) in Eastern Austria was investigated. From 1968-1983 302,643 boys were born, 68 of whom were subsequently identified as having Duchenne muscular dystrophy. The overall incidence with respect to live male births is 1:4451 (22.5 x 10(-5)). The mean age of the children at the occurrence of the first symptoms was 3.1 (SD 1.1), at first presentation to a physician 4.8 (SD 2.0), and at diagnosis 5.5 (SD 1.7) years. DMD occurred in 56 families. These families had 73 boys with DMD, 5 of whom were born before or after the observation period. Thirteen families had two affected boys and two families even had three. In 4 families a second boy suffering from DMD was born although the diagnosis of DMD had already been established in another close male relative. If a newborn male screening system had been in function, 13 cases could possibly have been avoided. However, since in 3 cases the affected siblings were not both born within the observation period, they were excluded, leaving 10 cases. Hence, a prevention rate of 14.7% might have been achieved through creatine kinase (CK) screening and genetic counselling.

Austria↗
PubMed1993

[Indicators for an impending need of artificial respiration in patients with muscular dystrophy].

In 1990 we examined 25 patients with Duchenne Muscular Dystrophy (DMD) or Spinal Muscular Atrophy type II (SMA-II). The purpose was to elucidate their general physical capability and find indicators for future need of artificial ventilation. We used interviews and measurements. The interviews were based on classifications described as 1) EAMDA, 2) VIGNOS, 3) BROOKE for use with DMD patients. Our own classification (called EK) is described and used. Moreover, we measured five parameters for the mechanical lung function, the strength of eight great muscle groups, and anthropometrical data. In January 1992, between two and 18 months after our examination, seven of the patients (all DMD) required artificial ventilation. Among the patients who needed artificial ventilation, we found the DMDs to have the lowest physical capability, as measured by the interview (EK and EAMDA) and the smallest values for forced vital capacity (FVC) and peak expiratory flow rate (PEF). All 11 patients with SMA-II could administer their lives without ventilator. Comparing their values with the DMD group, we would expect that several would need artificial ventilation. The reason why the SMA-II patients can manage without artificial ventilation is not clarified. Combining our classification (EK) and the value for FVC, we can predict the need for artificial ventilation among the participating DMD patients.

Adolescent↗
PubMed1993

[Rapid screening of the Duchenne muscular dystrophy gene deletion by two multiplex PCR].

Duchenne muscular dystrophy (DMD) is one of the most common lethal X-linked disorders. Partial intragenic deletions account for up to 60% of DMD deletions, and approximately one-third of all cases arise via new mutations. In this paper, two sets of primers were used for two multiplex PCR screenings of DMD gene deletions. The first set consists of 5 pairs of primers which amplify 5 exons with higher deletion frequencies, and the second set includes other 4 pairs of primers. Fifty-one DMD samples were screened by the first set, and then those not found to have deletions were screened by the second set. In total, 25 deletions were identified in the Fifty-one DMD samples: That is, about 49% of all cases studied were found to have deletions.

Base Sequence↗
PubMed1993

[Molecular genetics of Duchenne/Becker muscular dystrophy].

The X-linked gene responsible for Duchenne muscular dystrophy (DMD)/Becker muscular dystrophy (BMD) encodes dystrophin, a high-molecular-weight cytoskeletal protein. The identification of the dystrophin gene through positional cloning, and the subsequent description of its protein product have opened several new fields of research and genetic diagnosis. Studies in our laboratory revealed that 26 out of 47 (55%) cases of DMD and nine out of 12 (75%) cases of BMD exhibited genomic deletion. The DMD phenotype is associated with mutations that shift the reading frame of the message, whereas the BMD phenotype is associated with mutations that maintain the reading frame. Immunofluorescence microscopy has established dystrophin's distribution on the plasma membrane of muscles. DMD patients demonstrate a lack of dystrophin on their muscle cell membrane, whereas BMD patients produce a limited amount of protein or abnormally sized protein. Extensive studies on dystrophin and the gene may lead to an understanding of the cause for this and may allow development of a rational treatment for DMD to be developed.

Animals↗
PubMed1996

Molecular diagnosis of Duchenne muscular dystrophy in Singapore.

Duchenne muscular dystrophy (DMD) is a common lethal sex-linked recessive disorder. Seventy percent of the cases are inherited and 30% are due to mutations. The mainstay of prevention is detection of female carriers and antenatal diagnosis of affected foetuses. Before the era of molecular diagnosis, DMD has been clinically defined. Serum creatine kinase (CK) has also been used to screen women at risk for carrier status. With the isolation and sequencing of the DMD gene at Xp21 and the identification of the DMD gene-product dystrophin, DNA technology can be applied for the diagnosis of the affected, for the detection of carriers and in antenatal diagnosis. The multiplex polymerase chain reaction (PCR) technique offers a rapid and simple screening method for deletions of the gene. We were able to detect partial deletions which account for 58.3% of gene defects in our patients. This direct demonstration of the gene defect that causes DMD gives a 100% assurance of accuracy and specificity of the diagnosis. Linkage analysis is especially useful for prenatal diagnosis and carrier detection in the remaining 41.7% of families without detectable deletions or duplications. This approach however is indirect and is dependent on information on genotypes from affected males and key family members. With the availability of increasingly more restriction fragment length polymorphisms (RFLPs), it has become practical to use the haplotype method for accurate carrier detection and prenatal diagnosis.

DNA↗
PubMed1997

Uniparental disomy of the entire X chromosome in a female with Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a severe, progressive, X-linked muscle-wasting disorder with an incidence of approximately 1/3,500 male births. Females are also affected, in rare instances. The manifestation of mild to severe symptoms in female carriers of dystrophin mutations is often the result of the preferential inactivation of the X chromosome carrying the normal dystrophin gene. The severity of the symptoms is dependent on the proportion of cells that have inactivated the normal X chromosome. A skewed pattern of X inactivation is also responsible for the clinical manifestation of DMD in females carrying X;autosome translocations, which disrupt the dystrophin gene. DMD may also be observed in females with Turner syndrome (45,X), if the remaining X chromosome carries a DMD mutation. We report here the case of a karyotypically normal female affected with DMD as a result of homozygosity for a deletion of exon 50 of the dystrophin gene. PCR analysis of microsatellite markers spanning the length of the X chromosome demonstrated that homozygosity for the dystrophin gene mutation was caused by maternal isodisomy for the entire X chromosome. This finding demonstrates that uniparental isodisomy of the X chromosome is an additional mechanism for the expression of X-linked recessive disorders. The proband's clinical presentation is consistent with the absence of imprinted genes (i.e., genes that are selectively expressed based on the parent of origin) on the X chromosome.

Blotting, Southern↗
PubMed1997

Cardiac troponin T composition in normal and regenerating human skeletal muscle.

Cardiac troponin T (cTnT), measurement of which has been recommended for diagnosing myocardial infarction, was initially believed to be specific for the heart. However, recent publications have reported cTnT in sera of patients without cardiac disease; therefore, we investigated whether cTnT could be found in human skeletal muscle tissues. Using immunohistochemistry, Western blot, and quantitative cTnT ELISA, we assayed human heart (n = 3), normal human skeletal muscle (n = 6), and diseased skeletal muscle samples from patients with polymyositis (PM, n = 13) and Duchenne muscular dystrophy (DMD, n = 6). All heart specimens contained cTnT, but the expression of cTnT in normal skeletal muscle samples varied widely, ranging from no expression (quadriceps femoris) to expression by up to 20% of the muscle fibers (diaphragm). Immunohistochemistry detected cTnT in skeletal muscle of 8 of the PM patients and all of the DMD patients. Mean myofibrillar cTnT concentrations (mg/g myofibrillar protein) were: cardiac = 10.0, normal skeletal = 0.8, PM skeletal = 0.7, and DMD skeletal = 4.37, confirming the results of immunohistochemistry. Western blot analysis also confirmed the expression of cTnT in muscle from DMD patients. These findings provide evidence that cTnT is not 100% cardiac-specific but also is expressed in regenerating (PM and DMD) as well as in normal (nonregenerating) skeletal muscle.

Antibody Specificity↗
PubMed1997

[The effects of spinal fusion on respiratory function and quality of life in Duchenne muscular dystrophy].

We studied the functional outcome of spinal fusion for the surgical treatment of scoliosis in 8 patients with Duchenne muscular dystrophy (DMD). The mean age of DMD patients at the time of the surgery and the mean follow-up duration was 13.8 (12.3 to 15.4) and 3.9 (1.5 to 6.8) years, respectively. The average spinal angle (Cobb angle) was corrected from 58.8 to 28.6 degrees with the mean corrective rate of 51.3% by the surgical intervention. The correction rate was higher and the corrected Cobb angle remained unchanged during follow-up period in mildly scoliotic patients. Forced vital capacity (FVC) increased post-operatively in 3 patients with moderate scoliosis (Cobb angle: 50 to 80 degrees), indicating that the correction of spinal alignment is effective for the treatment of decreased thoracic volume in DMD. On the other hand, two cases with low % FVC (16.9% and 30.4%, respectively) had poor prognosis in respiratory status. Namely, one died of pneumonia at 17 months after the surgery and the other required mechanical ventilation via nasal mask at 3 years post surgery. Sitting balance improved in all patients, which resulted in more functional use of their upper extremities. During the follow-up period, all patients except one patient who died of pneumonia could maintain sitting balance without support. Moreover these included 2 patients over 20 year old. No complications related to spinal deformities have been found in these patients. Previous study in our hospital showed that 7 of 48 (14.6%) of DMD patients spent all their lives without apparent scoliosis (Cobb angle less than 30 degrees). These suggest that spinal fusion could be recommended for patients with Cobb angle more than 30 degrees and with % FVC more than 35%. Although the impact of spinal fusion upon the life expectancy remains unclear, favorable effect on respiratory function and quality of life can be expected for carefully selected patients with DMD.

Adolescent↗
PubMed1976

Diethylstilbestrol effects on serum enzymes and isozymes in muscular dystrophy.

Diethyistibestrol was administered orally to 11 boys with Duchene muscular dystrophy (DMD). Creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) activities, characteristically high in DMD, and presumably of muscle origin, were reduced significantly (P LESS THAN .05). On ther other hand, the activity of alkaline phosphatase, an enzyme not of muscle origin, increased. These enzyme changes were reversible when diethyistibestrol was discontinued. Despite appreciable alterations in totoal serum enzyme activity, no important change was found in the isozyme patterns. Piperazine estrone sulfate was administered to another patient with DMD. The effects of this physiologic hormone were, in part, similar to those of diethyistibestrol. Experimentally, diethylstilbestrol reduced the efflux of CPK and LDH from mouse skeletal muscle. This may be the manner by which diethylstilbesterol reduced the serum enzyme levels in DMD, but this has not been proved directly. These studies are the first step in an effort to identify various agents that in combinations may normalize serum enzyme levels.

Adolescent↗
PubMed1997

Increase in fetal breech presentation in female carriers of Duchenne muscular dystrophy.

Female carriers of Duchenne muscular dystrophy (DMD) may demonstrate elevated serum creatine kinase (CK) and reduction of muscle dystrophin in all muscle types. We hypothesized that decreased dystrophin in uterine or pelvic girdle musculature might affect the obstetrical performance of females heterozygous for a dystrophin mutation. We reviewed the outcome of 34 deliveries resulting in 35 children from 13 women who were mothers of males attending a muscular dystrophy clinic. Obstetrical performance was examined retrospectively by chart review and patient contact. Of 35 children, 6 (17%) were delivered in the breech position, which is a fivefold increase above the national standards for term pregnancies. Of the six infants with breech presentation, two were males affected with DMD, one was a female heterozygote, one was a male who died perinatally, and the carrier status of the other two females is unknown. Most DMD affected males (12/14) were delivered in the vertex position. Thus, it is likely that maternal, rather than fetal, muscle weakness was the significant factor in determination of fetal position at term. We speculate that subtle changes in uterine or pelvic girdle muscle tone may contribute to a higher rate of fetal breech position in carriers of the DMD gene.

Breech Presentation↗