Diseased human muscles

Considerable interest was aroused by the finding of Wieme and Lauryssens (W16) in 1962 that there is a change in the electrophoretic isoenzyme pattern of lactate dehydrogenase in diseased human muscle. The major isoenzyme of lactate dehydrogenase in most normal muscles moves slowest on electrophoresis (LDH 5), but in myopathic muscle the proportion of LDH 5 may be considerably reduced. This finding has been confirmed and extended by numerous workers, utilizing various techniques for isoenzyme differentiation (e.g., BIO, E5). The abnormal pattern is seen in most, but not all, cases of Duchenne dystrophy and in a variety of other muscular disorders. It may be evident in the very early stages of Duchenne dystrophy (P2) and is seen even in some female carriers of the disease (E3). 

H16. Hughes, B. P., Lactate dehydrogenase isoenzymes and phospholipids in normal and diseased human muscle. In Muscle Diseases, Proc. Int. Congr., Milan, 1969 (J. N. Walton, N. Canal, and G. Scarlato, eds.), pp. 294-296. Excerpta Med. Found., Amsterdam, 1970. 

Susheela, A. K., Free fatty acid concentrations in normal and diseased human muscle and in blood sera from patients with neuromuscular disease. Clin. Chim. Acta 22, 219-222 (1968). 

W16. Wieme, R. J., and Lauryssens, M. J., Lactate dehydrogenase multiplicity in normal and diseased human muscle. Lancet i, 433-434 (1962). 

In 2000, our studies were the first to demonstrate that abnormal accumulation of a-syn occurs in diseased human muscle and thus is not unique to brain disorders [30]. 

Identification of diseased states by P NMR originates from the observation of Burt et al. (1976) that intact dystrophic chicken muscle contains an extra resonance not present in normal chicken muscle. The compound giving rise to this signal has been isolated and identified as a phosphodiester, L-serine ethanolamine phosphate (Chalovich et al., 1977). At the same time, it was found that intact normal human leg muscle contains another phosphodiester, 5/i-glycerol 3-phosphorylcholine (GPC), and that this compound is missing in diseased human muscles, notably in Duchenne muscular dystrophy (Barany era/., 1977 Chalovich era/., 1979). This su ested that GPC may be used as a marker for human muscle diseases. 

Table II lists the GPC content of various diseased human muscles. Because the NC protein content of all diseased muscles was decreased considerably as compared to that of the value of 174 mg NC protein per gram for healthy muscle (column 2, Table 11), the GPC content is expressed as micromoles per 174 mg NC protein. Such a normalization permits detection of specific differences in phosphate profiles (Glonek et al., 1981).

Angiotensin-II AT, Human cDNA Artherosderosis, cardiac hypertrophy, congestive heart failure, hypertension, myocardial infarction, renal disease, cancer, diabetes, obesity, glaucoma, cystic fibrosis, Alzheimer s disease, Parkinson s disease Smooth muscle contraction, cell proliferation and migration, aldosterone and ADH release, central and peripheral sympathetic stimulation, extracellular matrix formation, tubular sodium retention, neuroprotection... 

Cardiac troponin subunits I and T are encoded by different genes than the respective skeletal muscle isoforms and have different amino acid sequences, giving them unique cardiac specificity. cTnl has never been shown to be expressed in normal, regenerating, or diseased human or animal skeletal muscle. By contrast, small amounts of cTnT are expressed as one of four identified isoforms in skeletal muscle during human fetal development, in regenerating rat skeletal muscle, and in diseased human skeletal muscle. cTnT isoform expression has been demonstrated in skeletal muscle specimens... 

Ricchiuti V, Apple FS. RNA expression of cardiac troponin T isoforms in diseased human skeletal muscle. Clin Chem 1999 45 2129-35. 

As first pointed out by Dreyfus et al. (Dll), the abnormal LDH isoenzyme pattern in diseased muscle resembles that of normal fetal muscle. In fact, in dystrophic chickens the normal adult isoenzyme pattern is never attained in the affected birds (D3), and possibly this is true of some human muscle diseases. An increase in the specific activity of many other glycolytic enzymes during development has been reported (B5, K3). 

Adenylate kinase, which is abundant in muscle as in many other tissues, decreases in dystrophic mouse and human muscle (H6, P7). This enzyme, by interconverting adenine nucleotides, probably functions in the control of glycolysis it seems reasonable to suppose, therefore, that its activity may be governed by the same factors which influence glycolytic enzymes, as discussed above. A severe decline in the activity of AMP deaminase occurs in muscular dystrophy (P6, P7) and also in denervated muscle (M12) and in some cases of muscle affected by hypokalemic periodic paralysis (E6). Skeletal muscle normally contains a higher concentration of this enzyme than other tissues in fact, it is almost absent from some, such as liver. Its physiological function, and hence the significance of the sharp decline in its activity in diseased muscle, is still a matter of speculation. 

Cell Based Delivery (Providence, Rl) Genetically modified human muscle stem cells for application in cardiovascular disease Preclinical... 

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