Myogenic defect in human muscular dystrophy

Thompson, Edward J.; Yasin, Rose; Beers, Gisela Van; Nurse, K.C.E.; Alani, S. M.

doi:10.1038/268241a0

Cited by 51 publications

(7 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When muscle is dissociated and the cells plated in culture, both myoblasts and fibroblasts are obtained and the rate of proliferation of the fibroblasts frequently exceeds that of the myoblasts. DMD muscle cultures have been compared with normal muscle cultures and a number of differences reported, including increased collagen synthesis (2), decreased specific activity of creatine kinase (3), increased ratio of nonmuscle to muscle creatine kinase isozymes (3-5), altered lipid biosynthesis (6), and clustered myotube morphology (5,7,8). However, it is unclear whether these differences are intrinsic to the DMD myoblasts and related to the disease or a reflection of the proportion of fibroblasts present in the mixed cultures analyzed.…”

mentioning

confidence: 99%

Defective myoblasts identified in Duchenne muscular dystrophy.

Blau¹,

Webster²,

Pavlath³

1983

Proc. Natl. Acad. Sci. U.S.A.

293

199

View full text Add to dashboard Cite

A defect in the proliferative capacity of satellite cells, mononucleated precursors of mature muscle fibers, was found in clonal analyses of cells cultured from Duchenne muscular dystrophy (DMD) patients. The total yield of myoblasts per gram of muscle biopsy was decreased to 5% of normal. Of the DMD myoblast clones obtained, a large proportion -contained a morphological class of flat distended cells that had an increased generation time and ceased to proliferate beyond 100-1,000 cells but could be induced to fuse and form myotubes. The altered muscle phenotype was detected in all cultures from DMD patients but was rarely found among myoblasts of controls. By age 14 yr, it comprised as many as 90% of DMD myoblasts. The remaining DMD myoblast clones, which initially grew well, had severely impaired proliferative capacity upon passage and further cultivation. Eventually all myoblasts from DMD muscle tissue exhibited defective growth potential. In contrast, the fibroblast yield and proliferative capacity from DMD samples did not differ from normal. Based on these findings, we propose a hypothesis for the etiology of DMD: Dividing myoblasts are required for muscle growth and maintenance, and the limited capacity of DMD myoblasts to grow is directly related to the progressive muscle degeneration characteristic of the disease.Duchenne muscular dystrophy (DMD) is a chronic, lethal Xlinked disease that affects 1 in 4,800 males (1). Although DMD is well defined clinically, the cellular and biochemical basis for the disease is unknown. A major problem in the biological study of muscular dystrophy has been the heterogeneous nature of muscle tissue. Muscle is composed of a mixture of cell types present in variable ratios, especially in disease states. When muscle is dissociated and the cells plated in culture, both myoblasts and fibroblasts are obtained and the rate of proliferation of the fibroblasts frequently exceeds that of the myoblasts. DMD muscle cultures have been compared with normal muscle cultures and a number of differences reported, including increased collagen synthesis (2), decreased specific activity of creatine kinase (3), increased ratio of nonmuscle to muscle creatine kinase isozymes (3-5), altered lipid biosynthesis (6), and clustered myotube morphology (5,7,8). However, it is unclear whether these differences are intrinsic to the DMD myoblasts and related to the disease or a reflection of the proportion of fibroblasts present in the mixed cultures analyzed.We have developed methods for obtaining pure populations of human myoblasts that can be studied under standardized conditions (9). Our methods use postnatal muscle as a source.Consequently, the myoblasts obtained in culture are muscle satellite cells, the mononucleated myoblasts of mature muscle fibers, positioned between the basement membrane and the sarcolemma (10). It is these satellite cells that are capable of proliferating in vitro (11, 12) and are probably responsible for postnatal muscle regeneration and fiber growth in vivo. We have...

show abstract

mentioning

confidence: 99%

Defective myoblasts identified in Duchenne muscular dystrophy.

Blau¹,

Webster²,

Pavlath³

1983

Proc. Natl. Acad. Sci. U.S.A.

293

199

View full text Add to dashboard Cite

show abstract

“…37-39 Other research observed unusual clusters of "sticky cells" formed by dissociated muscle of patients with Duchenne and Becker muscular dystrophies, a sign which reflects abnormal collagen production. 40 Mutations in genes coding for collagen type VI are also responsible for congenital muscular dystrophies including Bethlem myopathy and Ullrich congenital muscular dystrophy. 41 Many serum proteins have been identified as biomarkers which reflect the pathogenesis of DMD; the concentration of 23 identified mouse serum proteins exhibited an increase while four other proteins were found to exist at concentrations significantly lower in mdx mice as compared to healthy control mice in one study.…”

Section: Discussionmentioning

confidence: 99%

Diagnosis of Duchenne Muscular Dystrophy using Raman Hyperspectroscopy

Ralbovsky

Dey

Galfanoa

et al. 2020

Preprint

View full text Add to dashboard Cite

Duchenne muscular dystrophy (DMD) is the most common and severe form of muscular dystrophy and affects boys in infancy or early childhood. DMD is known to trigger progressive muscle weakness due to skeletal muscle degeneration and ultimately causes death. There are limited treatment regimens available that can either slow or stop the progression of DMD. An accurate and specific method for diagnosing DMD in its earliest stages is needed to prevent progressive muscle degeneration and death. Current methods for diagnosing DMD are often laborious, expensive, invasive, and typically diagnose the disease later on it is progression. In an effort to improve the accuracy and ease of diagnosis, this study focused on developing a novel method for diagnosing DMD which combines Raman hyperspectroscopic analysis of blood serum with advanced statistical analysis. Partial Least Squares Discriminant Analysis (PLS-DA), was applied to the spectral dataset acquired from control and mdx blood serum of 3-and 12-month old mice to build a diagnostic algorithm. Internal cross-validation showed 95.2% sensitivity and 94.6% specificity for identifying diseased spectra. These results were verified using external validation, which achieved 100% successful classification efficiency at the level of individual donor. This proof-of-concept study presents Raman hyperspectroscopic analysis of blood serum as a fast, nonexpensive, minimally invasive and early detection method for the diagnosis of Duchenne muscular dystrophy.

show abstract

“…Our previous studies suggested that the basic disorder in DMD is misdirected regeneration with a tendency to synthesize more collagen than contractile protein due t o a defect in translation [ 6 ] . However, recent studies show alterations of internal cell membranes in DMD that might result in defective protein synthesis by changing the relative amounts of membrane-bound versus free iibosomes as a result of higher membrane viscosity [14,151. Electron microscopic examination of DMD cells in culture has shown several ultrastructural abnormalities that suggest an increase in synthesis of protein for export (collagen) and/or for incorporation into the cell membrane.…”

Section: Discussionmentioning

confidence: 99%

Discriminant analysis of ribosomal protein synthesis findings in carrier detection of duchenne muscular dystrophy

1980

View full text Add to dashboard Cite

Previous studies have shown that in vitro muscle ribosomal protein synthesis (RPS) by monomeric ribosomes (MR) and total polyribosomes (TPR) and collagen synthesis (CS) are significantly increased (P less than 0.01) in 47 known carriers of Duchenne muscular dystrophy as compared to 60 age-matched controls. However, there was considerable overlap of the distribution of controls and carriers, particularly for monomeric ribosomal protein synthesis and collagen synthesis. To improve detection of carriers we used discriminant analysis utilizing logs of each measurement as superior to a univariate or bivariate scheme. This study considered four groups: proven carriers (30) (group 1), presumptive carriers (female relatives of Duchenne patients with high serum creatine kinase (CK) levels) (32) (group 2), controls greater than or equal to 20 years old (42) (group 3) and controls less than 20 years (36) (group 4). Comparison of groups, Misclassification (%), (see chart). These results suggest that discriminant analysis reduces the misclassification rates as compared with univariate or bivariate analysis and confirm the superiority of RPS measurements as a carrier test for Duchenne muscular dystrophy.

show abstract

Myogenic defect in human muscular dystrophy

Cited by 51 publications

References 13 publications

Defective myoblasts identified in Duchenne muscular dystrophy.

Defective myoblasts identified in Duchenne muscular dystrophy.

Diagnosis of Duchenne Muscular Dystrophy using Raman Hyperspectroscopy

Discriminant analysis of ribosomal protein synthesis findings in carrier detection of duchenne muscular dystrophy

Contact Info

Product

Resources

About