ABSTRACT
OBJECTIVE: Muscle biopsies from chronic steroid (glucocorticoid) myopathy, non-steroid histochemical type-2 fiber atrophy, and muscle denervation patients were studied to determine if their glycogen contents, or enzymes involved in glycogenolysis and glycolysis might be related to their fiber atrophy. DESIGN AND METHODS: Fast frozen muscle biopsies from the above patients and from patients later judged by histochemistry to be normal were assayed enzymatically for glycogen content, for enzymes involved in glycogenolysis, and for 6 of the enzymes involved in glycolysis. RESULTS AND CONCLUSION: All three groups of patients had glycogen content, but only the chronic steroid myopathy muscle had statistically less glycogen content than did normal human muscle. All 3 groups had statistically low mean values compared to normal muscles for glycogen phosphorylase activity. This suggests that the biosynthesis and phosphorolysis of glycogen are not involved in muscle fiber atrophy, and glucocorticoid administration does not activate muscle glycogen biosynthesis. Histochemical type-2 fiber atrophy muscles were low compared to normal muscles in three glycogenolysis enzyme activities plus four glycolysis enzyme activities. Muscles from denervation patients were low compared to normal muscles in three glycogenolysis enzyme activities plus five glycolysis enzyme activities. This suggests that muscle denervation may lower the rate of glycolysis enough to fail to provide sufficient pyruvate for mitochondrial ATP biosynthesis, resulting in insufficient protein biosynthesis in both fiber types.
Subject(s)
Glycogenolysis , Glycolysis , Muscle Denervation , Muscle, Skeletal/innervation , Muscle, Skeletal/pathology , Muscular Atrophy/pathology , Muscular Diseases/pathology , Adult , Aged , Female , Glycogen/metabolism , Humans , Male , Middle Aged , Muscle, Skeletal/cytology , Muscle, Skeletal/enzymology , Muscular Atrophy/enzymology , Muscular Diseases/enzymologyABSTRACT
We report two patients in whom phosphoglycerate mutase (PGAM) deficiency was associated with the triad of exercise-induced cramps, recurrent myoglobinuria, and tubular aggregates in the muscle biopsy. Serum creatine kinase (CK) levels were elevated between attacks of myoglobinuria. Forearm ischemic exercise tests produced subnormal increases of venous lactate. Muscle biopsies showed subsarcolemmal tubular aggregates in type 2 fibers. Muscle PGAM activities were markedly decreased (3% of the normal mean) and molecular genetic studies showed that both patients were homozygous for a described missense mutation (W78X). A review of 15 cases with tubular aggregates in the muscle biopsies from our laboratory and 15 cases with PGAM deficiency described in the literature showed that this clinicopathological triad is highly suggestive of PGAM deficiency.
Subject(s)
Exercise Tolerance/genetics , Muscle, Skeletal/enzymology , Muscular Diseases/enzymology , Myoglobinuria/enzymology , Phosphoglycerate Mutase/deficiency , Adolescent , Adult , Black or African American/genetics , Biopsy , Creatine Kinase/blood , DNA Mutational Analysis , Exercise Test , Female , Humans , Inclusion Bodies/enzymology , Inclusion Bodies/genetics , Inclusion Bodies/pathology , Ischemia/enzymology , Ischemia/genetics , Ischemia/physiopathology , Male , Middle Aged , Muscle Cramp/enzymology , Muscle Cramp/genetics , Muscle Cramp/physiopathology , Muscle, Skeletal/pathology , Muscle, Skeletal/physiopathology , Muscular Diseases/diagnosis , Muscular Diseases/genetics , Mutation, Missense , Myoglobinuria/genetics , Myoglobinuria/physiopathology , Phosphoglycerate Mutase/genetics , Sarcoplasmic Reticulum/enzymology , Sarcoplasmic Reticulum/pathologyABSTRACT
Gene expression in archived frozen sural nerve biopsies of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) was compared to that in vasculitic nerve biopsies (VAS) and to normal nerve (NN) by DNA microarray technology. Hierarchical clustering analysis demonstrated distinct gene expression patterns distinguishing these disease groups. Of particular interest were: (1) Tachykinin precursor 1, which may be involved in pain mediation; (2) Stearoyl-CoA-desaturase, which may be a marker for remyelination and (3) the Allograft Inflammatory Factor 1 (AIF-1), a modulator of immune response during macrophage activation. Differential gene expression may help distinguish between CIDP, VAS and NN in sural nerve biopsies and identify genes that may be involved in disease pathogenesis.
Subject(s)
Demyelinating Diseases/genetics , Demyelinating Diseases/pathology , Gene Expression Profiling/methods , Polyneuropathies/genetics , Polyneuropathies/pathology , Adult , Aged , Chronic Disease , Female , Humans , Male , Middle Aged , Oligonucleotide Array Sequence Analysis/methods , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction/genetics , Sural Nerve/pathology , Up-RegulationSubject(s)
Diabetic Neuropathies/diagnosis , Diabetic Neuropathies/therapy , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/diagnosis , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/therapy , Demyelinating Diseases , Diabetic Neuropathies/cerebrospinal fluid , Evoked Potentials, Motor , Humans , Immunoglobulin G/therapeutic use , Immunosuppressive Agents/therapeutic use , Muscle, Skeletal/physiopathology , Nerve Fibers, Myelinated/physiology , Neural Conduction , Plasma Exchange/methods , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/cerebrospinal fluid , Reaction Time , Sick LeaveABSTRACT
Areflexic quadriplegia that occurs in the intensive care unit (ICU) is commonly ascribed to critical illness polyneuropathy based upon electrophysiology or muscle light microscopy. However, electron microscopy often documents a selective thick filament loss myopathy. Eight ICU patients who developed areflexic quadriplegia underwent biopsy. Seven patients had received steroids, and 2 had also received paralytic agents. Electrodiagnostic studies revealed absent or low-amplitude motor responses in 7. Sensory responses were normal in 5 of 6 and absent in 1. Initial electromyography revealed absent (n = 3), small (n = 3), or polyphasic (n = 1) motor unit potentials, and diffuse fibrillation potentials (n = 5). In all 8, light microscopy of muscle revealed numerous atrophic-angulated fibers and corelike lesions, and electron microscopy revealed extensive thick filament loss. Morphology of sural and intramuscular nerves, and, in one autopsied case, of the obturator nerve and multiple nerve roots, was normal. Although clinical, electrodiagnostic, and light microscopic features mimicked denervating disease, muscle electron microscopy revealed thick filament loss, and nerve histology was normal. This suggests that areflexic ICU quadriplegia is a primary myopathy and not an axonal polyneuropathy.
Subject(s)
Critical Care , Critical Illness , Quadriplegia/pathology , Adult , Aged , Electrodiagnosis , Female , Humans , Male , Microscopy, Electron , Middle Aged , Muscle, Skeletal/innervation , Muscle, Skeletal/pathology , Muscle, Skeletal/ultrastructure , Myosins/metabolism , Neurons/pathology , Peripheral Nerves/pathology , Peripheral Nerves/ultrastructure , Plastic Embedding , Reflex/physiology , Sural Nerve/pathology , Sural Nerve/ultrastructureABSTRACT
Leg muscle was biopsied and frozen for storage at -70 degrees C. from 5 wild-type mice, two knocked out acid alpha-glucosidase (GAA) gene mice, and seven glycogen synthase plus glucose muscle transporter transgenic mice. All of the wild-type mice had very little muscle glycogen (3.58 +/- 1.67 micromols glucosyl subunits per g muscle), and 52% or more of its glycogen phosphorylase activity without AMP (69% +/- 17% glycogen phosphorylase a). In contrast the GAA knockout and transgenic mice had glycogen ranging from 63 to 297 micromols glucosyl subunits per g muscle, and very little or no glycogen phosphorylase activity without 1.00 mM AMP (4.8% and less glycogen phosphorylase a). This suggests that there is an inverse relationship between mouse muscle phosphorylase a and the muscle's glycogen content.