The amyloid beta-protein precursor is localized in smooth muscle cells of leptomeningeal vessels

We examined leptomeningeal vessels using 2 different antisera which recognized both terminal ends of amyloid beta-protein precursor (APP). Both antisera recognized a 120-kDa protein from leptomeningeal vessels. Immunocytochemistry showed that APP was localized in the smooth muscle cells of leptomeningeal vessels. These results indicated that the smooth muscle cells of leptomeningeal vessels contained full-length native APP, and that the cerebrovascular amyloid in the leptomeningeal vessels was derived from this APP.     

Reciprocal change of motor-evoked potentials preceding voluntary movement in humans

Reciprocal change of motor-evoked potentials (MEPs) recorded from the agonist and antagonist muscles of the forearm was studied in 10 normal subjects in whom transcranial magnetic stimulation (TMS) was applied to the hand motor area before voluntary wrist movements. MEP recorded from the agonist muscles, that is, radial extensor muscles for wrist extension and ulnar flexor muscle for wrist flexion, were gradually facilitated with shortening of the interval between the magnetic stimulation and the voluntary muscle contraction. In contrast, MEP recorded from the antagonist muscles, that is, ulnar flexor muscle for wrist extension and radial extensor muscles for wrist flexion, were gradually suppressed as the interval shortened. The reciprocal change of MEP was recognized when TMS was applied within 60 ms prior to the voluntary movements. The present data confirmed that reciprocal change of MEP was recognized before voluntary movements; they further suggest that cortically originated reciprocal control of the corticospinal pathway may exist and that it may be generated just before the voluntary movement. © 1996 John Wiley & Sons, Inc.     

Identification of a Ca2+-ATPase in cerebellar Purkinje cells

The expression of a sarcoplasmic reticulum (SR)-like Ca2+-ATPase was studied in the adult chicken cerebellum. A monoclonal antibody. CaS/C1-IgG, specific for the cardiac/slow-twitch skeletal muscle SR Ca2+-ATPase, was used as a probe of protein expression. An immunoblot analysis showed that CaS/C1-IgG recognized similar size polypeptides in adult chicken heart and cerebellum. CaS/C1-IgG recognized fragments of similar size after limited tryptic digestion of cardiac and cerebellar membranes. A two-dimensional alpha-chymotryptic peptide map analysis demonstrated that the cardiac and cerebellar Ca2+-ATPases were structurally very similar. Immunofluorescence microscopy localized the cerebellar Ca2+-ATPase to Purkinje cell bodies and dendritic trees. These results suggest that the well-known Ca2+ uptake system of skeletal and cardiac muscle SR has a remarkably similar counterpart in some neurons.     

Lung and respiratory muscle function in facioscapulohumeral muscular dystrophy

Pulmonary dysfunction is not a well‐recognized feature of facioscapulohumeral muscular dystrophy (FSHD). The aim of this study was to establish the prevalence and type of pulmonary and respiratory muscle dysfunction in FSHD. Sixteen patients with moderately advanced FSHD and 16 healthy controls were evaluated. Standard lung and respiratory muscle function tests were performed. Diaphragm muscle inspiratory action was evaluated with transdiaphragmatic pressure measurements. Lung function tests showed an increased residual volume in five patients. There was a significant difference in global respiratory muscle function in patients versus controls; weakness was mild, and it affected expiratory more than inspiratory muscles. There was no significant difference in the diaphragm inspiratory action of patients versus controls. The dystrophic process that underlies FSHD did not significantly involve the muscles of the diaphragm, but it caused mild global respiratory muscle weakness that affected expiratory more than inspiratory muscles. It is probably not necessary to routinely monitor respiratory muscle function in ambulant FSHD patients who lack symptoms or signs of respiratory impairment. Muscle Nerve, 2009     

Phosphoglycerate kinase deficiency: Another cause of recurrent myoglobinuria

A 14-year-old boy had myoglobinuria and renal failure after intense exercise; a year earlier he had experienced a milder episode. There was no consanguinity and no family history of neuromuscular diseases or hemolytic anemia. Strength was normal. Forearm ischemic exercise caused prolonged contracture with no rise of venous lactate. Muscle morphology showed only a mild increase of lipid droplets. Glycogen concentration was normal. Muscle phosphoglycerate kinase (PGK) activity was 5% of the normal mean, and all other glycolytic enzymes were normal. The residual PGK activity of muscle was heat stable but showed slower than normal electrophoretic mobility and decreased Michaelis constants for 3-phosphoglycerate and adenosine triphosphate. The enzyme defect was also expressed in erythrocytes and in fibroblast and muscle cultures. PGK activity was decreased in tissues from the patient's mother but normal in the father. PGK deficiency is an X-linked recessive trait usually associated with hemolytic anemia, mental retardation, and seizures; myopathy had not been recognized previously. Muscle PGK deficiency is now added to two other newly recognized glycolytic defects, phosphoglycerate mutase and lactate dehydrogenase deficiencies, as a cause of recurrent myoglobinuria.     

Study of human muscle biopsies with muscle glycogen storage diseases using 1H nuclear magnetic resonance spectroscopy (NMRS)--analysis of perchloric acid extracts of muscles]

Muscle metabolites of perchloric acid extracts in human muscle biopsies including the cases with muscle glycogen storage diseases (GSD) were analyzed using 1H NMR spectroscopy. Several metabolites such as lactate, pyruvate, creatine, phosphocreatine, acetate, alanine, carnitine and glycogen were recognized. The cases with GSD III and GSD V showed two broad signals at 3.60 and 3.85 ppm which were considered to be the proton signals from the accumulated glycogen. However, in GSD III, the signal at 3.60 ppm was high compared with that at 3.85 ppm suggesting that glycogen was increased in its degree of branching joined by alpha-1,6 linkage. These data suggest that 1H NMR spectroscopy is a useful and simple technique for analysis of muscle glycogen storage diseases as well as lipid myopathies.     

Immunoblot analysis of circulating antibodies against muscle proteins in amyotrophic lateral sclerosis and other neurologic diseases

Serum from patients with amyotrophic lateral sclerosis (ALS) was tested by immunoblotting for reactivity against three muscle-derived preparations: denervated chick leg muscle extracts, media conditioned by denervated rat hemidiaphragms, and a human muscle extract. For each preparation, multiple bands were present using serum from all patients and controls, and no band was unique to ALS. Against rat muscle-conditioned medium, bands in the 56,000 (56K) molecular weight range were present to an equal degree in ALS and in controls; in addition, different bands near 56K were recognized by serum from different ALS patients. These results fail to confirm a recent report suggesting that anti-56K reactivity is characteristic of ALS.     

Myopathy in primary systemic amyloidosis

Involvement of the peripheral nervous system by amyloidosis is common. It is less well recognized that amyloid can directly infiltrate and weaken skeletal muscle. We report a case of a 73-year-old woman, known to have cardiac amyloidosis, who developed profound weakness secondary to amyloid myopathy. Review of the 8 other well documented cases in the literature has revealed a rather homogeneous syndrome. Proximal weakness, muscle stiffness, pseudohypertrophy and myalgia constitute the principal features. This syndrome usually develops in cases with well recognized generalized amyloidosis. Amyloid is deposited within the basal lamina of blood vessels and muscle fibers.     

Comparison of the ultrastructural myopathy induced by anticholinesterase agents at the end plates of rat soleus and extensor muscles

Rats were treated with single subcutaneous injections of the irreversible AChE inhibitors, sarin (90 to 100 micrograms/kg) or soman (55 micrograms/kg), and with chronic doses of the reversible carbamate inhibitor, pyridostigmine. In surviving animals with severe behavioral symptoms, we examined the end-plate regions of the slow-twitch soleus and the fast-twitch extensor digitorum longus muscles, using the electron microscope. Within 30 min, sarin administration caused a recognizable subjunctional myopathy. The progress of morphologic damage was followed for 7 days, during which time the occurrence of damage diminished. The initial swelling of subjunctional organelles and vacuole generation progressed to the point where nerve terminals and attached postjunctional folds were lifted away from the muscle surface. This appeared to be caused by a combination of enlarging vacuoles and insertion of Schwann and macrophage cells into the lesions, and was followed by degeneration of the postjunctional folds. A new component of anti-AChE myopathy was recognized: progressive swelling of chromatin in subjunctional muscle nuclei. The soleus muscle was considerably more sensitive to these effects than the extensor muscle. Soman had a much less prominent ultrastructural effect on the muscle end plates. Chronic pyridostigmine treatment had effects similar to those of a single sarin injection on the soleus as well as a pronounced effect on the extensor muscle.     

T cell recognition of muscle acetylcholine receptor in ocular myasthenia gravis

We examined the proliferative response of blood CD4(+) cells to muscle acetylcholine receptor (AChR) subunits and the epitope repertoire of the epsilon and gamma subunits, in ocular myasthenia gravis (oMG) patients and healthy subjects. oMG patients seldom recognized all subunits. The frequency and intensity of recognition was the same for all subunits, irrespective of the disease duration. The responses in oMG were lower than in generalized myasthenia gravis. Healthy subjects had frequent, low responses to one or more subunits. oMG patients recognized several epitopes on the gamma and epsilon subunits, that partially overlapped those recognized in gMG. The subunits and epitopes recognized by individual oMG patients changed over time. Thus, oMG patients have minimal and unstable sensitization of anti-AChR CD4(+) cells, in agreement with their low and inconsistent synthesis of anti-AChR antibody.     

Pathology of eosinophilic fasciitis and its relation to polymyositis

The anatomical substrate of eosinophilic fasciitis (EF) was studied in 15 muscle biopsy specimens of this disease, six of which included the dermis and subcutaneous tissue. As controls, 94 postmortem muscle specimens from patients dying of non-muscular diseases were used. Of these 94 specimens, 22 (23.4%) showed practically no deep fascia and 72 specimens showed a single dense bundle of collagen with no distinction between deep fascia and epimysium. The 15 specimens of EF showed thickening and inflammatory infiltration of varying degrees in the deep fascia, epimysium, perimysium, endomysium and also in muscle. We conclude that the anatomical substrate of EF is not confined to the deep fascia, but involves other structures including mysia and muscle itself. Most reported cases of EF in the literature do not even describe muscle. A comparative study of 15 biopsy specimens of polymyositis and dermatomyositis with those of EF revealed only quantitative differences in the histopathological changes of muscle and mysia, inflammatory infiltrate and eosinophilia. We suggest that the diseases are more closely related than previously recognized.     

Metabolic myopathy in canine muscle-type phosphofructokinase deficiency

In vivo 31phosphorus nuclear magnetic resonance spectroscopy (P-NMR) of the anterior tibialis muscle was used to investigate the metabolic myopathy of inherited muscle-type phosphofructokinase (PFK) deficiency in four (homozygous) dogs who had mild exercise intolerance, rare muscle cramps, increased serum creatine kinase activity, but no myoglobinuria. During isometric muscle work induced by indirect electrical stimulation, and subsequent recovery, changes in the ratio of phosphocreatine (PCr) and inorganic phosphates (Pi) were comparable in muscle of PFK-deficient and normal dogs and indicated a large capacity for arobic oxidative phosphorylation in canine muscle. The progressive accumulation of sugar phosphates (PME) during graded exercise clearly demonstrated the glycolytic block in PFK-deficient dogs. During a muscle contracture, induced by acute muscle stimulation, PFK-deficient muscle became completely depleted of PCr and ATP, accumulated large amounts of PME, and recovered very slowly. We conclude that PFK-deficient dogs have a metabolic myopathy that demonstrated some but not all the features recognized in the human disorder.     

Adult thymus expresses an embryonic nicotinic acetylcholine receptor-like protein

The subunit composition of acetylcholine receptor-like protein(s) (AChR-LP) expressed by normal thymus was investigated. In skeletal muscle, the AChR exists in two forms, an embryonic form which contains the gamma-subunit and an adult form where the gamma-subunit is substituted by a different, homologous subunit called epsilon. Antibodies against unique sequence segments of the embryonic gamma-subunit and of the adult epsilon-subunit of bovine muscle AChR, in addition to antibodies specific for the alpha-, beta-, and delta-subunits of bovine muscle AChR, were used to probe immunoblots of AChR-LP(s) from bovine thymus. Subunits of approximate Mr 41 kDa, 48-54 kDa, 57 kDa and 67-72 kDa were recognized by anti-alpha, anti-beta, anti-gamma and anti-delta antibodies respectively. Anti-epsilon antibodies did not recognize any protein band from bovine thymus. AChR-LP similar or identical to the embryonic muscle AChR is therefore expressed in normal thymus.     

Infantile lipid storage myopathy with nocturnal hypoventilation shows abnormal low-affinity muscle carnitine uptake in vitro.

An infant with respiratory insufficiency, cardiomyopathy, lipid storage myopathy and low muscle carnitine was diagnosed as having 'Ondine's curse' because of recurrent nocturnal hypoventilation. Carnitine uptake was studied in 20-day-old cultured muscle, where two distinct saturable transport components are recognized: the high- and low-affinity-uptake. Experimental evidence suggests that low-affinity-uptake is muscle-specific, operating at physiological carnitine concentration. In the patient's cultured myotubes, the low-affinity-uptake K(m) was 260% of controls (P < 0.01), whereas kinetic parameters of high-affinity uptake were normal. The high K(m) indicates an immature or altered carnitine muscle carrier, which may decrease the physiologic carnitine uptake.     

Silent period in the mentalis muscle induced by facial nerve and cutaneous stimulation.

The aim of this study was to demonstrate that silent periods of the mentalis muscle are induced after facial nerve stimulation and cutaneous stimulation in normal subjects. When the marginal mandibular branch of the facial nerve and the cutaneous nerve in areas adjacent to the lower lip were stimulated during slight voluntary contraction of the mentalis muscle, silent periods were elicited with surface electrodes on the mentalis muscle. The early phase and the late phase of the silent period were elicited by marginal mandibular branch stimulation. The early phase of the silent period was recognized following the F waves and it disappeared at 36.3 msec. The average duration of the late phase of the silent period was 59.2 msec, with an average latency of 62.5 msec. Only the late phase of the silent period after cutaneous stimulation could be elicited, with a duration and latency of 55.9 msec and 54.0 msec respectively. The authors conclude that the silent period is able to be elicited in the mentalis muscle by peripheral nerve stimulation, and is one of the late responses in facial muscles.     

A missing sphincteric component of the gastro-oesophageal junction in patients with GORD

Abstract  It was recently shown that the tonic pressure contribution to the high-pressure zone of the oesophago-gastric segment (OGS) contains the contributions from three distinct components, two of which are smooth muscle intrinsic sphincter components, a proximal and a distal component [ J Physiol 2007; 580.3 : 961 ]. The aim of this study was to compare the pressure contributions from the three sphincteric components in normal subjects with those in gastro-oesophageal reflux disease (GORD) patients. A simultaneous endoluminal ultrasound and manometry catheter was pulled through the OGS in 15 healthy volunteers and seven patients with symptomatic GORD, before and after administration of atropine. Pre-atropine (complete muscle tone), postatropine (non-muscarinic muscle tone plus residual muscarinic tone) and subtracted (pure muscarinic muscle tone) pressure contributions to the sphincter were averaged after referencing spatially to the right crural diaphragm and the pull-through start position. In the normal group, the atropine-resistant and atropine-attenuated pressures identified the crural and two smooth muscle sphincteric components respectively. The subtraction pressure curve contained proximal and distal peaks. The proximal component moved with the crural sling between full inspiration and full expiration and the distal component coincided with the gastric sling-clasp fibre muscle complex. The subtraction curve in the GORD patients contained only a single pressure peak that moved with the crural sphincter, while the distal pressure peak of the intrinsic muscle component, which was previously recognized in the normal subjects, was absent. We hypothesize that the distal muscarinic smooth muscle pressure component (gastric sling/clasp muscle fibre component) is defective in GORD patients.     

Neonatal arthrogryposis and absent limb muscles: a muscle developmental gene defect?

We describe a child who presented at birth with arthrogryposis. Following a muscle biopsy a diagnosis of congenital muscular dystrophy was made and a skin biopsy 12 years later confirmed the presence of merosin. Her clinical picture was unusual, however, for merosin-positive congenital muscular dystrophy. She had extreme wasting and weakness of her arms and legs. In contrast, she had good neck and trunk control, and no facial or respiratory muscle weakness. We have used magnetic resonance imaging to examine the pattern of muscle involvement in this case. No recognizable muscle could be identified in the limbs. In contrast, the axial muscles were preserved. This striking pattern of virtual absence of muscles in the limbs with sparing of the axial muscle suggests that a gene responsible for the migration and/or proliferation of limb muscle precursor cells may be involved in the disease process. It is recognized that merosin-positive congenital muscular dystrophy is a heterogeneous disease. Magnetic resonance imaging is a useful tool for examining in detail the pattern of muscle involvement and identifying individual phenotypes. Understanding more about which muscles are affected in children with congenital myopathies may provide information on the underlying pathological process and help in the search for candidate proteins and genes.     

Delay in the maturation of muscle fibers in infants with congenital hypotonia

Muscle biopsies of hypotonic children have shown delayed maturation of a fetal type of muscle fibers: subsarcolemmal halo devoid of activity for mitochondrial dehydrogenases, type II predominance and in some cases abnormal dispersion of fiber diameter. Fiber subtypes within group II were also abnormal. One case has definite embryonic characteristics with presence of myoblasts. Not a single clinical pattern was present in these patients and a variety of associated disorders were recognized. Some patients had a clinical picture corresponding to congenital benign hypotonia as described by Walton.     

A case of polymyositis associated with Kawasaki disease

We report a 3-year-old boy with proximal painful muscle weakness associated with Kawasaki disease. The muscle biopsy revealed inflammatory cell infiltration with vasculopathy. This unique coexistence of polymyositis and Kawasaki disease is quite uncommon and suggests a newly recognized complication during Kawasaki disease.     

Familial spastic paraplegia with syndrome of continuous muscle fiber activity (Isaacs)

A woman aged fifty-three developed paraparesis at the age of 4, which progressed slowly and required crutches by the age of 30. At the age of 51, muscle stiffness involved bilateral hands and arms gradually. At the age of 53, she suffered from painful spasms in right deltoid muscle. Her two brothers had spastic paraplegia without other neurological deficits. Her paternal grandfather and maternal grandmother were cousins. Slight dementia was noted (WAIS: IQ, 79). Her posture was stiff and muscles of upper limbs were in a persistent contraction; Subcutaneous tissue was thin, and muscles were well-defined and firm. There was moderate muscle weakness of legs and hands. Continuous fasciculations and myokymias were recognized in muscles of the arms and the limb girdles. Muscle tone was considerably increased especially in the bilateral arms. The deep tendon reflexes were exaggerated with extensor plantar responses. Profuse sweating affected palms, soles and backs. No sensory disturbance was appreciated. There was no myotonic responses to percussion of muscles. Following laboratory data were normal; thyroid functions, CSF studies, anti HTLV-I antibody and long chain fatty acid in red blood cells, myelography and brain CT except for increased basal metabolic rate (53%). Electromyographic study in the arms and hands revealed spontaneous motor unit activities including doublets at rest and increased proportion of polyphasic potentials and high amplitude potentials in voluntary contraction. Biopsy of right quadriceps femoris muscle showed hypertrophy of type I fibers and angulated atrophy of type II fibers. Continuous muscle activities in upper limbs did not change at sleep or with intravenous administration of 7 mg diazepam.(ABSTRACT TRUNCATED AT 250 WORDS)