Progressive muscular dystrophies

In the course of studies on other pathological amino acidurias, the accompanying peptiduria has also been observed by many authors. Rapp de Eston et al. (R2) observed a marked increase in the excretion of both free amino acids and peptides in patients with diffuse hepatic necrosis. Using a simplified chromatographic method adapted to clinical purposes and suitable for analysis of amino acids excreted with urine, Skarzynski et al. (S5) demonstrated a raised level of a certain peptide which is always present in normal urine in smaller quantities, as well as the appearance of some new peptides in cases of jaundice and liver cirrhosis. Some abnormal peptide spots were also detected on the chromatograms in cases of progressive muscular dystrophy (K4) and in patients irradiated with X-rays (S2). 

Progressive muscular dystrophy is an afBiction of all mankind. In the United States alone there are said to be some 200,000 cases (probably an overestimate), of whom almost two thirds are children feebly awaiting gross distortion and early death by the rapid Duchenne type. 

B13. Berger, H., Aminoaciduria in progressive muscular dystrophy. Symposium international Recherches actuelles sur le muscle. I. Muscle squdettique. Rev. Can. Biol. 21, 567 (1962). 

B21a. Buchthal, F., and Rosenfalck, P., Electrophysiological aspects of myopathy with particular reference to progressive muscular dystrophy. In Muscular Dystrophy in Man and Animals (G. H. Bourne and M. N. Golarz, eds.). Chapter VI, pp. 193-262. Karger, Basel, 1963. 

D19. Dubowitz, V., Progressive muscular dystrophy of the Duchenne type in females and its mode of inheritance. Brain 83, 432 (1960). 

El. Ebashi, S., Toyokura, Y., Momoi, H., and Sugita, H., High creatine phos-phokinase activity of sera of progressive muscular dystrophy patients. J. Biochem. Tokyo) 46, 103 (1959). 

Jl. Jackson, C. E., and Carey, J. H., Progressive muscular dystrophy autosomal recessive type. Pediatrics, 77 (1961). 

K9. Konieczny, L., Noworytko, J., and Samecka-Keller, M., Investigations on the chemical symptomatology of progressive muscular dystrophy. Arch. Polon. Med. Interne 28, 1579 (1958). 

Mil. Minot, A. S., Frank, H., and Dziewatkowski, D., The occurrence of pentose and phosphorus containing complexes in the urine of patients with progressive muscular dystrophy. Arch. Biochem. 20, 394 (1949). 

P3. Pearce, G. W., and Walton, J. N., Progressive muscular dystrophy the histo-... 

Pll. Perkoff, G. T., and Tyler, F. H., Studies in disorders of muscle XI. The problem of pentosuria in progressive muscular dystrophy. Metab. Clin. Exptl. 5, 563 (1956). 

Rl. Reinhold, J. G., and Kingsley, G. R., The chemical composition of voluntary muscle in muscle disease A comparison of progressive muscular dystrophy with other diseases together with a study of the effects of glycine and creatine therapy. /. Clin. Incest. 17, 377 (1938). 

R8. Ronzoni, E., Berg, L., and Landau, W., Enzyme studies in progressive muscular dystrophy. Res, Puhl, Assoc. Res. Nervous Mental Disease 38, 721-729 (1961). 

Singh, S. D., and Somani, I. K., Serum lactic acid dehydrogenase levels in progressive muscular dystrophy in children. Indian Fractit. 16, 433 (1963). 

Sugita, H., Serum creatine phosphokinase and aldolase activity in patients with neuromuscular disorders. I. Progressive muscular dystrophy. Psychiat. Neurol. Japan. 62, 106 (1960). 

Tl. Tada, K., Wanatabe, Y., and Chikaoka, H., Demonstration of defect of creatine phosphokinase in muscle of progressive muscular dystrophy. Tohoku J. Exptl. Med. 75, 299 (1961). 

V2. Vignos, P, J., Jr., and Lefkowitz, M., A biochemical study of certain skeletal muscle constituents in human progressive muscular dystrophy. /. CUn, Inoest. 38, 873 (1959). 

W9. West, W. T., and Murphy, E. D., Histopathology of hereditary, progressive muscular dystrophy in inbred strain 129 mice. Anat. Record 137, 279 (1960). 

Blood enzyme tests can detect the abnormalities associated with progressive muscular dystrophy early on, even before symptoms are clearly evident. Muscle tissue is rich in creatine and, when muscles are diseased, the creatine leaks into the blood and can be measured as creatine kinase (CK). The normal level of CK is about 160 lU/L, but an individual with Duchene muscular dystrophy may have CK levels as high as 15,000-35,000 lU/L. If the diagnosis is in doubt, genetic studies and muscle biopsy can also be done. The recent isolation of the Duchenne gene and the discovery that dystrophin is the abnormal encoded protein makes a precise molecular diagnosis possible. It also offers hope that the genetic basis for other dystrophies will be discovered soon. 

Smith CL, Bush GH. Anaesthesia and progressive muscular dystrophy. Br J Anaesth 1985 57(11) 1113-18. 

Certain diseases, such as the progressive muscular dystrophies, appear to involve a failure of the affected tissues to... 

The distributions of isoenzymes of aldolase, LD, and CK in the muscles of patients with progressive muscular dystrophy have been found to be similar to those in the earlier stages of development of fetal muscle. The isoenzyme abnormalities in dystrophic muscle have been interpreted as a failure to reach or maintain a normal degree of differentiation. Isoenzyme patterns in regenerating tissues may also show some tendency to approach fetal distributions. This tendency may result from relaxation or modification of control systems in rapidly dividing cells and may account for some of the isoenzyme changes noted (e.g., in muscle in acute polymyositis). 

Serum CK activity is greatly elevated in all types of muscular dystrophy. In progressive muscular dystrophy (particularly Duchenne sex-linked muscular dystrophy), enzyme activity in serum is highest in infancy and childhood (7 to 10 years of age) and may be increased long before the disease is clinically apparent. Serum CK activity characteristically falls as patients get older and as the mass of functioning muscle diminishes with the progression of the disease. About 50% to 80% of the asymptomatic female carriers of Duchenne dystrophy show threefold to sixfold increases of CK activity, but values may be normal if specimens are obtained after patients have experienced a period of physical inactivity. Quite high values of CK are noted in... 

Japanese workers (KIO) have reported the occasional appearance of NAD in the urine of patients with progressive muscular dystrophy. Coenzyme A is said to be decreased in the muscle and increased in the serum of patients (Rl). Such changes probably reflect increased leakage of these nucleotides from diseased muscle fibers rather than changes in their metabolism. 

A3. Askanas, W., Identification of the agent responsible for the abnormal immuno-electrophoretie pattern of serum in Duchenne s progressive muscular dystrophy. Life Sci. 6, 1767-1773 (1966). 

Jl. Jacobs, H., Okabe, K., Yue, R., Keutel, H., Ziter, F., Palmieri, R., Tyler, F., and Kuby, S. A., A comparison of normal human ATP-creatine transphosphorylases with those from progressive muscular dystrophy tissues. Fed. Proc. Fed. Amer. Soc. Exp. Biol. 28, 346 (1969). 

KIO. Kondo, F., Abe, E., and Ikeda, M., Occasional appearance of diphosphopyridine nucleotide in urine of patients with progressive muscular dystrophy. Tohoku J. Exp. Med. 91, 191-199 (1967). 

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