George H. Cardinet

Polysaccharide storage myopathy associated with recurrent exertional rhabdomyolysis in horses

A polysaccharide storage myopathy is described in nine Quarterhorses, Quarterhorse crossbreds, American Paints and Appaloosa horses which had a history of recurrent exertional rhabdomyolysis. Muscle biopsies were characterized by high muscle glycogen concentrations with up to 5% of type 2 muscle fibers containing inclusions which stained positively with the periodic acid Schiff (PAS) stain. The inclusions were classified as an acid mucopolysaccharide, based on their histochemical staining characteristics. Ultrastructural studies revealed that the inclusions were composed of beta glycogen particles interspersed among arrays of filamentous material. In addition, many type 2 fibers contained multiple subsarcolemmal vacuoles. These vacuoles stained lightly with eosin and did not stain positively with PAS. Centrofascicular atrophy and necrosis of scattered type 2 fibers were present in biopsies from some horses. No glyco(geno)lytic enzyme deficiencies were identified using a biochemical screening test for anaerobic glycolysis. Attempts to measure branching enzyme activities in both affected and control samples were unsuccessful, employing methods developed for human muscle. The polysaccharide accumulation in these horses may represent a hereto yet undefined metabolic disorder of skeletal muscle.

Skeletal Muscle Function

Publisher Summary This chapter discusses skeletal muscle function. Muscular contraction results in the transformation of chemical energy into mechanical energy or shortening. The energy for contraction is derived from the hydrolysis of adenosine triphosphate (ATP) to adenosine diphosphate (ADP) and inorganic phosphate; this hydrolysis is catalyzed by adenosine triphosphatase. ATP required for contraction is produced in mitochondria by oxidative phosphorylation and in the sarcoplasm by glycogenolysis and glycolysis. Muscle may use ATP directly from those sources or indirectly from phosphorylation of ADP by the dephosphorylation of creatine phosphate in the presence of creatine phosphokinase. The morphological and functional unit of skeletal muscles is the motor unit. The motor unit consists of (1) the moto neuron, the cell body of which lies in the anterior or ventral horn of the spinal cord and the axon of which extends along the anterior or ventral root and peripheral nerve; (2) the neuromuscular junctions; and (3) the myofibers innervated by the neuron. The use of muscle biopsies in the evaluation of neuromuscular disorders allows examination of myofibers, neuromuscular junctions, intramuscular nerve branches, connective tissues, and blood vessels. Therefore, the application of histochemical techniques in conjunction with routine light and electron microscopic examination of muscle biopsies offers the potential to evaluate and integrate the pathoanatomical, biochemical, and physiological manifestations of neuromuscular disorders.

Cloning of bovine muscle glycogen phosphorylase cDNA and identification of a mutation in cattle with myophosphorylase deficiency, an animal model for McArdle's disease

Genetic defects of myophosphorylase in humans cause a metabolic myopathy (McArdles disease) characterized by exercise intolerance, cramps, and recurrent myoglobinuria. Recently, a breed of cattle with myophosphorylase deficiency has been identified: this is the first animal model of McArdles disease. To define the molecular genetic error in the cattle, we cloned and sequenced the wild-type bovine myophosphorylase cDNA. Homology to human cDNA is 95.8% for the amino acid sequence, and 92.0% for the nucleotide sequence. Sequence homology to rabbit cDNA is 97.3% in amino acid, 90.8% in nucleotide. In the cDNA fragments amplified by RT-PCR from muscle RNA of the cattle with myophosphorylase deficiency, we identified a C-to-T substitution, changing an encoded arginine (CGG) to tryptophan (TGG) at codon 489. The mutant residue is adjacent to pyridoxal phosphate binding sites and to an active site residue, and the sequence around this mutation is highly conserved in different species.

Myasthenia gravis and polymyositis in a dog following fetal hematopoietic cell transplantation.

Myasthenia gravis and focal polymyositis occurred in a dog following successful transplantation of DLA-identical fetal liver hematopoietic cells. There was no evidence of acute or chronic graft-versus-host disease. Antibodies to acetylcholinesterase receptor and immune complexes reactive with myoneural junctions were demonstrated, as well as focal inflammation with perifascicular and type 2 muscle atrophy. The dog responded to treatment with prednisolone and pyridostigmine.

Chapter 16 – Skeletal Muscle Function

Publisher Summary Skeletal muscles comprise approximately 50% of the bodys weight; hence, skeletal muscle cells (myofibers) constitute the largest mass of cells in the body that have similar morphological and physiological properties. The protoplasmic properties of contractility and conductility that characterize myofibers are an expression of specialized sarcoplasmic organelles, principally membranes and filaments, which are highly ordered and compartemtalized to serve those functions which in turn impart a distinctive morphology to the myofibers. Studies of muscles have provided excellent examples of the integration of form and function, whereby molecular and organelle structure and function can be directly related to cellular morphology and function, which in turn can be related to the morphology and function of the organs and organisms they serve. This chapter attempts to outline the great diversity that exists in skeletal muscles. By so doing, it is hoped that the knowledge and techniques developed over the past three decades will find their rightful introduction and application to increase recognition and understanding of neuromuscular disorders in clinical veterinary medicine.

Transmission of Creutzfeldt-Jakob Disease to the Stumptail Macaque (Macaco arctoides)

Summary The successful transmission of Creutzfeldt-Jakob disease from both affected human and chimpanzee brain to stumptail macaques has been accomplished. The incubation period of 5 yr was the same for both animals; however, the course of the disease was longer in the animal receiving the human brain. In both cases, initial mild symptoms slowly remitted only to reappear some 4 mo later. Muscle biopsies revealed changes suggestive of a mild neuropathy. In addition, there appeared to be an increased ability to incorporate 3H-thymidine in untreated cultures of lymphocytes from peripheral blood.