Dystrophy

DNA sequence data have been used to investigate inherited diseases such as hemophilia and muscular dystrophy, and also in cancer research. 

Deriva.tives, The most important derivatives of 1,2,3,4-benzenetetrol are the ubiquiaones, eg, coenzyme Q, which are dimethoxytoluquiaones with polyisoprenoid side chains (61). They occur ia plants and animals. Mice with hereditary muscular dystrophy have a deficiency of coenzyme Q ia their heart and hind leg muscles. Therapeutic adrninistration of coenzyme Q /7339-63-5] produces physical improvement and a significantly prolonged lifespan (212). Coenzyme Q also has been used to treat deafness when adrninistered either orally or parenteraHy (213). 

Inositols, ie, hexaliydrobenzenehexols, are sugars that have received increasing study and are useful in the treatment of a wide variety of human disorders, including vascular disease, cancer, cirrhosis of the Hver, frostbite, and muscular dystrophy (269). Myoinositol esters prepared by reaction with lower fatty acid anhydrides are useful as Hver medicines and nonionic surfactants the aluminum and ammonium salts of inositol hexasulfate are useful anticancer agents (270). Tetraarjloxybenzoquinones are intermediates in the preparation of dioxazine dyes (266,271). The synthesis of hexakis(aryloxy)benzenes has also beenpubUshed (272). 

In 1956 selenium was identified (123) as an essential micronutrient iu nutrition. In conjunction with vitamin E, selenium is effective iu the prevention of muscular dystrophy iu animals. Sodium selenite is adrninistered to prevent exudative diathesis iu chicks, a condition iu which fluid leaks out of the tissues white muscle disease iu sheep and infertility iu ewes (see Eeed ADDITIVES). Selenium lessens the iacidence of pneumonia iu lambs and of premature, weak, and stillborn calves controls hepatosis dietetica iu pigs and decreases muscular inflammation iu horses. White muscle disease, widespread iu sheep and cattle of the selenium-deficient areas of New Zealand and the United States, is insignificant iu high selenium soil areas. The supplementation of animal feeds with selenium was approved by the U.S. EDA iu 1974 (see Eeed additives). Much of selenium s metaboHc activity results from its involvement iu the selenoproteia enzyme, glutathione peroxidase. 

Duchenne muscular dystrophy gene (at 2.4 megabases, the largest known gene in any organism)... 

The Molecular Defect in Dnchenne Muscular Dystrophy Involves an Actin-Anchoring Protein... 

Worton, R., 1995. Mnscnlar dystrophies Diseases of die dystrophin-glycoprotein complex. Science 270 755-756. 

Calpain Tissue specific calpains have been implicated in diabetes, cataracts, multiple sclerosis, and limb-girdle muscular dystrophy type 2A. More than 50 inhibitors of calpain have described which have a potential for therapeutic applications. 

LGMD, limb girdle muscular dystrophy DMD, Duchenne muscular dystrophies BMD, Becker muscular dystrophies... 

The newest molecular addition to Cl- channels are bestrophins [5]. There are four different bestrophin isoforms in humans. Mutations in Bestl cause Best macular dystrophy, hence their name. All four isoforms induce chloride currents when expressed heterologously. Although they show a dependence on intracellular calcium, their biophysical properties differ from Ca-activated chloride currents typically observed in native cells. Mutagenesis experiments changed the activation of currents and induced slight changes in ion selectivity, lending support to the hypothesis that bestrophins themselves are Cl- channels. 

Skeletal Muscle Disorders An Introduction The Muscular Dystrophies... 

The Xp21-Linked Muscular Dystrophies Emery-Dreifuss Muscular Dystrophy (EDMD) Facioscapulohumeral Muscular Dystrophy (FSH)... 

To cover these various disorders in an orderly and comprehensive manner, the following sections are devoted, respectively, to the muscular dystrophies the congenital myopathies the metabolic myopathies the myotonias, periodic paralyses, and malignant hyperpyrexia the neurogenic disorders the inflammatory muscle disorders the endocrine myopathies and the drug-induced and toxic myopathies. 

Figure 1. Immunofluorescent labeling of dystrophin in the Xp21 muscular dystrophies. In normal muscle, clear uniform labeling is present at the membrane of each muscle fiber. In Becker muscular dystrophy (BMD), there is inter- and intrafiber variation in labeling intensity. In Duchenne muscular dystrophy (DMD), most fibers are devoid of labeling (note, however, that in most biopsies occasional fibers exhibit weak labeling). In the biopsy from a manifesting carrier, some fibers show normal labeling and others are negative. In the former, the normal X-chromosome is active while in the latter the abnormal X-chromosome is active.

Figure 2. Erb s illustration of the pathology of muscle from patients with Duchenne muscular dystrophy. Note the variation in muscle fiber diameter, fiber-splitting, deposition of fat and infiltration of connective tissue. Drawing from several biopsies produced during final decade of 19th century. 

EDMD is another X-linked muscular dystrophy, clinically and genetically completely distinct from DMD and BMD. Affected boys usually have onset in childhood of contractures (especially involving the Achilles tendons, elbows, and spinal muscles), humeroperoneal muscle weakness, and cardiac conduction defects, which tend to be mostly a problem in adult life and may necessitate insertion of a pacemaker. The gene for EDMD is known to map to Xq28, but this localization is... 

Severe Childhood Autosomal Recessive Muscular Dystrophy of Childhood (SCARMD)... 

The only one of these conditions which causes progressive and degenerative disease of muscle is myotonic dystrophy. Inheritance is autosomal dominant, but expression is very variable. The condition also illustrates the phenomenon of... 

Myotonic dystrophy AD 19q13 Myotonin protein kinase Muscle chloride channel... 

The histopathological features of muscle samples from patients with myotonic dystrophy are not particularly distinctive. Early changes appear to be a selective atrophy of type 1 fibers, and hypertrophy of type 2 fibers, but the biochemical and/or physiological basis of these possibly related phenomena is not known. The incidence of degenerating fibers increases with age, although the presence of internally nucleated muscle fibers in early stages of the disease suggests that the muscle retains... 

Congenital myotonic dystrophy is a relatively rare condition in which myotonia (defined electrically) is mostly absent in the affected newborn infant, but becomes apparent in the older infant. Histopathology shows a consistent feature of arrested development and maturation of muscle fibers, but there is, currently, no adequate explanation for this phenomenon. Patients with congenital myotonic dystrophy rarely survive without aggressive ventilatory support, and survivors, without exception, are severely multiply handicapped. 

There is no single underlying cause for the myotonia seen in the muscles of myotonic patients. The typical myotonic response is a train of action potentials generated in a muscle fiber in response to a single stimulus. Experimental work has shown that such a response can be generated in normal muscle fibers in which chloride conductance is suppressed, and this may be the cause of the myotonia of Thomsen s disease (see Barchi, 1988 for examples). It is almost certainly not the cause of myotonia in myotonic dystrophy in which there is an associated fall in... 

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