Kenneth K. Kaiser

THREE "MYOSIN ADENOSINE TRIPHOSPHATASE" SYSTEMS: THE NATURE OF THEIR pH LABILITY AND SULFHYDRYL DEPENDENCE:

demomistnatiomi of ademiosi mie tn phosphatase ac tivity, two types of striated muscle fibers (Padykula amid Herman. J. Histochem. Cylochem 3: 170. 1955) can be distimiguished. These have been described as the less active type I and the more active type II fibers. It has beemi noted previously (Brooke amid Kaiser. J. Histochem. Cytochem. 17: 431. 1969; (uth amid Samaha. Exp. Neur. 25: 138. 1969) that the ademiosimie triphosphatase (ATPase) systems imi striated muscle fibers have diffenemit

Duchenne muscular dystrophy: Patterns of clinical progression and effects of supportive therapy

Two-hundred eighty-three boys with Duchenne dystrophy and 10 with Becker dystrophy have been followed for up to 10 years in a protocol that accurately measured their function, strength, contractures, and back curvature. Clinical heterogeneity is noted. Patients whose muscles were stronger were more likely to die from a cardiomyopathy. Weaker patients died from respiratory failure. A series of milestones is defined, which is of use in following the illness in an individual patient. This approach permits a scoring system that allows the severity of the disease to be defined in an individual boy. Evaluation of physical therapy and surgical intervention shows that night splints and scoliosis surgery are effective forms of treatment.

Comparison of muscle fiber typing by quantitative enzyme assays and by myosin ATPase staining.

Fibers in cross sections of human and rat muscle were typed by using histochemical ATPase stains, and the results were compared with those of quantitative enzyme assays of fragments of the same fibers dissected from serial freeze-dried sections. Two enzymes previously used to assess the metabolic type were measured in each case: lactate dehydrogenase and either adenylokinase (human fibers) or malate dehydrogenase (rat fibers). With human fibers there was essentially complete agreement between ATPase staining and the metabolic enzyme assays in distinguishing types I and II fibers. The agreement was less consistent with regard to type IIA and IIB fibers. A number of ATPase type IIC fibers were identified in one human muscle, and were found to fall between ATPase types I and IIA on the basis of metabolic enzyme assay results. Rat-fiber ATPase types I, IIA, and IIB from the plantaris muscle were rather well segregated on a two-dimensional lactate dehydrogenase-malate dehydrogenase grid. In the rat soleus muscle, ATPase types I and IIA fibers were shifted to lower lactate dehydrogenase levels, with IIC fibers interposed between them.

Acetazolamide‐responsive myotonia congenita

We have studied 14 patients from a kindred with an auto-somal dominant form of myotonia, with features differing from most cases of autosomal dominant or recessive myotonia congenita. All patients had painful muscle stiffness that was provoked by fasting and oral potassium administration and was relieved by carbohydrate-containing foods. Muscle biopsies showed the presence of type 1, 2A, and 2B fibers, as opposed to the absence of type 2B fibers seen in some patients with myotonia congenita. Acetazolamide was dramatically effective in alleviating myotonia in all patients and was more effective than other antimyotonic agents.

Controlled trial of thyrotropin releasing hormone in amyotrophic lateral sclerosis

A double-blind controlled trial of thyrotropin releasing hormone (TRH) 150 mg IM daily in 30 patients with amyotrophic lateral sclerosis is reported. The drug/placebo was administered for 2 months, followed by a 2-month “wash-out.” Evaluation of strength, functional ability, and respiratory functions was performed. A temporary increase in the strength of some muscles was detected following the administration of TRH, but no change in functional performance was noted. Neither the patients nor the investigators believed the effects were of any marked clinical significance. The course of the illness was not altered.

Appearance in Slow Muscle Sarcolemma of Specializations Characteristic of Fast Muscle after Reinnervation by a Fast Muscle Nerve

Abstract We utilized quantitative freeze-fracture electron microscopy to study the plasticity of orthogonal clusters of 60-A particles (the “square array”) found in the sarcolemma of fast-twitch muscle. The membrane macromolecular composition of normally slow-twitch rat soleus muscle was examined 1 year after surgical reinnervation by the nerve from fast-twitch extensor digitorum longus muscles. The isometric contraction times and histochemical profiles were monitored and it was confirmed that conversion of fiber types had occurred. The sarcolemma of the switched “fast” soleus developed square arrays of 60-A particles characteristic of fast-twitch muscle whereas the sarcolemma of the contralateral control, the “slow” soleus, contained only random particles. Square array density per square micrometer in cross-reinnervated fast soleus fibers resembled that of normal fast extensor digitorum longus muscles and varied as a function of distance from the neuromuscular junction. This experiment demonstrates that the appearance of these unusual clusters of 60-A particles is neuronally regulated. We further suggest that these macromolecules are under the influence of the same subtle aspects of innervation that regulate the differentiation of myosin adenosine triphosphatase and thereby the contractile behaviors of fast- and slow-twitch muscle. The function of the sarcolemmal square array is unknown; however, a correlation with a membrane property that is more highly developed in fast-twitch muscle is to be expected.

Effect of Duchenne muscular dystrophy on enzymes of energy metabolism in individual muscle fibers

Individual muscle fibers from patients with Duchenne muscular dystrophy at an early stage in their disease, and from apparently normal boys of similar age, were analyzed for 13 enzymes of energy metabolism. This approach avoided the serious problems with muscle homogenate assays from increases in nonparenchymal components and permitted assessment of disease changes in different fiber types. Some enzymes of glycogenolysis (phosphorylase, phosphoglucomutase, and pyruvate kinase) were decreased in dystrophic fibers of all types. Phosphofructokinase was decreased in presumptive type II fibers. Lactate dehydrogenase was increased in type I fibers and essentially unchanged in type II. Phosphoglucoisomerase was near normal. Two enzymes of glucose metabolism not involved in glycogenolysis, hexokinase and glycogen synthase, were near normal, but a third, fructose bisphosphatase, was sharply reduced. Two enzymes of oxidative metabolism, citrate synthase, and beta-hydroxyacyl CoA dehydrogenase, were unchanged or increased. Two enzymes of high energy phosphate transfer, creatine kinase and adenylokinase, were only marginally affected. The net result is to leave the type II fibers, which normally exert the greatest force, with a severe deficit in the glycogenolytic enzyme machinery to maintain that force.

McArdle's disease with myoadenylate deaminase deficiency Observations in a combined enzyme deficiency

Exercise and work potential of a patient with coexistent myophosphoryhse and myoadenylate deaminase (AMPDA) deficiency was compared with that of three patients with myophosphorylase deficiency alone. The patient with the combined defect failed to produce an abnormal rise in serum ammonia or hypoxanthine as seen in the other patients after forearm exercise. Maximum oxygen consumption and work rates during cycle egometer testing were similar in all patients, but well below controls. The occurrence of two defects involving short-term energy metabolism in muscle presents an opportunity to define further the metabolic role of AMPDA.

Exercising muscle does not produce hypoxanthine in adenylate deaminase deficiency

The failure of forearm exercise to increase plasma hypoxanthine in subjects with adenylate deaminase deficiency confirms this enzymes role in hypoxanthine production by normal forearm exercise. The conversion of adenosine monophosphate (AMP) to hypoxanthine may reflect an alternative method of adenosine triphosphate (ATP) regeneration in working muscle.

Forearm exercise increases plasma hypoxanthine.

Plasma hypoxanthine was measured in three normal subjects during aerobic forearm exercise. The comparative increase of hypoxanthine greatly exceeded that of ammonia or lactate. It is proposed that hypoxanthine production reflects ATP breakdown in muscle. The test may prove useful in the investigation of patients with metabolic muscle disease.