bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of D‐penicillamine on neuromuscular transmission in rats
Authors: Aldrich Michael S. , Kim Yong I. , Sanders Donald B.
Published: January 2005

Treatment of patients with D‐penicillamine (D‐P) has been associated with a syndrome similar to myasthenia gravis (MG). To explore this association, we examined the effects of D‐P on neuromuscular transmission in rat muscle. In the first experiment, bath‐applied D‐P had no significant effect on either miniature endplate potential (MEPP) amplitude or action potential (AP) amplitude. Endplate potential (EPP) amplitude and spontaneous MEPP frequency decreased significantly at concentrations approximately 40 times the maximum human therapeutic level. In the second experiment, rats receiving D‐P by daily injections for 33 to 37 days did not differ from controls in any of the measured electrophysiologic characteristics. Electron microscopy of muscle endplates from rats treated with D‐P showed no evidence of degeneration or simplification. In all cases, thymus histology by light microscopy was normal, and no antireceptor antibodies were found. Thus, D‐P has a mild direct presynaptic effect on neuromuscular transmission at high concentrations, but this effect is too small to account for the weakness seen in the myasthenia‐like syndrome in humans.
Polyaxonal myelination in developing dystrophic and normal mouse nerves
Authors: Brown Mark J. , Radich Sandra J.
Published: January 2005

Myelin‐forming Schwann cells in the peripheral nervous system characteristically surround and myelinate only single axons. Polyaxonal myelination is an anomaly of this one‐to‐one relationship whereby one normal‐appearing Schwann cell myelinates multiple axons. We examined the ventral roots and the proximal sciatic and posterior tibial nerves of developing normal mice and of dy2J/dy2J dystrophic mice with proximal failure of myelination. Polyaxonal myelination was a rare feature in normal nerves. Examples of polyaxonal myelination were observed six times more often in dystrophic than in normal mice and were most abundant in proximal sciatic nerves. Polyaxonal myelination could result from either an axonal or a Schwann‐cell abnormality, or it may be the nonspecific response of uncommitted Schwann cells to an early failure of myelination.
Congenital muscular dystrophy: Case reports and reappraisal
Authors: Lazaro Reynaldo P. , Fenichel Gerald M. , Kilroy Anthony W.
Published: January 2005

We report four cases of congenital muscular dystrophy; all demonstrated hypotonia and multiple contractures at birth. Strength remained stationary or improved, but the tendency for contracture formation persisted. Brief small amplitude polyphasic potentials were recorded on electromyography, and muscle biopsy revealed extensive fat and/or collagen replacement, which was out of proportion to fiber necrosis or patient strength. The consistent clinical and pathologic features of these patients and others described in the literature justify considering this disorder to be a specific nosologic entity.
Fatty acid biosynthesis in wallerian degeneration of rat sciatic nerve
Authors: Koeppen Arnulf H. , Papandrea John D. , Mitzen Edward J.
Published: January 2005

In‐vitro fatty acid biosynthesis was studied in normal rat sciatic nerve and during wallerian degeneration. Normal nerve incorporated 1,3‐C14‐malonyl‐CoA and 1‐C14‐acetyl‐CoA into fatty acids by a de‐novo biosynthetic pathway. The reaction product with highest radioactivity was palmitic acid, and the free fatty acids of nerve contained 90% of the total fatty acid label. During wallerian degeneration, there was a rapid increase of fatty acid biosynthesis that reached a peak between 16 and 24 days after nerve section. Values declined to normal levels at approximately 50 days.
Biochemistry of muscle membranes in Duchenne muscular dystrophy
Authors: Rowland Lewis P.
Published: January 2005

In Duchenne muscular dystrophy, as in other genetic diseases, there must be a biochemical abnormality. This fundamental genetic fault has not been identified, but several indirect lines of evidence suggest that the surface membranes of skeletal muscle are affected. The biochemical evidence implies abnormal egress of soluble enzymes and other proteins from muscle, abnormal permeability, and altered properties of membrane‐bound enzymes. As a result of the presumed genetic abnormality, functional properties are altered, and impaired regulation of intracellular calcium content could be responsible for the hallmarks of the disease—progressive weakness and degeneration of muscle. The evidence is by no means conclusive, however, and some of it is contradictory. Technical advances must be made before isolated membranes can be characterized biochemically. Other theories are also being evaluated.
Application of the freeze fracture technique to the study of human neuromuscular disease
Authors: Schotland Donald L. , Bonilla Eduardo , Yoshihiro Wakayama
Published: January 2005

This is a review of the application of the freeze fracture technique to the study of human neuromuscular disease. The advantages and limitations of the method are discussed, and the application of the technique is illustrated by a study of skeletal muscle plasma membrane in Duchenne muscular dystrophy.
Facilitatory effects of 4‐aminopyridine on normal neuromuscular transmission
Authors: Kim Yong I. , Goldner Marcia M. , Sanders Donald B.
Published: January 2005

The effects of 4‐aminopyridine (4‐AP) on neuromuscular transmission were studied in vitro in the rat flexor digitorum longus muscles. 4‐AP produced dose‐dependent increases in endplate potential (EPP) amplitude, in rise time to peak, and in the average number of acetylcholine quanta released by presynaptic nerve impulses. The neuromuscular blocking effects of d‐tubocurarine or low Ca2+/high Mg2+ concentrations could be completely reversed by 4‐AP, and EPPs developed into muscle action potentials (APs). The drug had minimal effects on the amplitude or frequency of spontaneous miniature endplate potentials, but increased the duration of indirectly elicited muscle APs. The action of 4‐AP required the presence of extracellular Ca2+; thus, its effect may be to promote Ca2+ entry into the motor nerve terminal, and thereby increase the neurally evoked transmitter release. 4‐AP is effective in overcoming both presynaptic and postsynaptic blockade of neuromuscular transmission, suggesting a potential role for this drug in the treatment of neuromuscular diseases.
“Snapping bottom”: Subluxation of the tendon of the long head of the biceps femoris muscle
Authors: Rask Michael R.
Published: January 2005

Subluxation of the tendon of origin of the long head of the biceps femoris muscle (or snapping bottom) is a rare, previously unreported degeneration of the tendinous attachment of the muscle at the ischial tuberosity. It occurs in a patient who wears out this attachment through a lifetime of hyperflexion hip movements, such as are required in bending to reach the floor. The snapping of the tendon across its point of origin causes pain and swelling in the buttock. In the older nonathlete, if conservative measures fail, the treatment of choice is simple tenotomy. The condition should not be confused with weaver's bottom (ischiogluteal bursitis), even though it may be a cause for that bursitis.
Superior gluteal nerve entrapment syndrome
Authors: Rask Michael R.
Published: January 2005

Entrapment of the superior gluteal nerve can occur as a result of compression by anterior‐superior tendinous fibers of the piriformis muscle and cause aching claudication‐type buttock pain, weakness of abduction of the affected hip with a waddling gait, and tenderness to palpation in the area of the buttock superolateral to the greater sciatic notch. Instilling anesthetic into the point of entrapment may relieve the pain completely, but superior gluteal neurolysis may be required to effect a permanent cure.
Measurement of acetylcholine receptor and anti‐receptor antibodies by ELISA
Authors: Norcross N. L. , Griffith I. J. , Lettieri J. A.
Published: January 2005

Both acetylcholine receptor (AChR) and antibodies capable of binding to the AChR can be measured using the recently developed enzymelinked immunosorbent assay (ELISA). The assay is very sensitive and reproducible. Because of the relative simplicity of the ELISA in comparison to radioimmunoassay procedures currently used to measure anti‐AChR antibodies, the ELISA may prove valuable as a clinical diagnostic tool for the human disease myasthenia gravis.
Changes in sarcomere length following tenotomy in the rat
Authors: Baker James H. , Hall‐Craggs E. C. B.
Published: January 2005

The medical belly of the gastrocnemius and the extensor digitorum longus muscles of rats were tenotomized. One day following tenotomy, the mean sarcomere length of the fast medial gastrocnemius was 1.8 μm, a value comparable to that of tenotomized slow soleus. The mean sarcomere length of the tenotomized extensor digitorum longus, however, was 2.0 μm, a figure which differed significantly from the values obtained for both the soleus and the gastrocnemius. Histological preparations showed the presence of central core degeneration in slow fatigue‐resistant fibers of the tenotomized gastrocnemius comparable to that seen in the soleus. No changes were found in the fibers of the tenotomized extensor digitorum longus. The fact that central core lesions were produced in the fibers of soleus and medial gastrocnemius but not in the extensor digitorum longus may be related to the lesser reduction in sarcomere length following tenotomy of the latter muscle.
Muscle phosphofructokinase deficiency: Two cases with unusual polysaccharide accumulation and immunologically active enzyme protein
Authors: Agamanolis Dimitris P. , Askari Ali D. , Di Mauro Salvatore , Hays Arthur , Kumar Kusum , Lipton Mark , Raynor Andrew
Published: January 2005

Two patients with phosphofructokinase (PFK) deficiency had exercise intolerance and increased serum activity of creatine kinase; one presented with hemolytic anemia, hyperuricemia, and gouty arthritis. The glycogen concentration in the muscle of these patients was about twice normal. PFK activity was virtually absent in muscle, but antibodies against the M subunits of the normal human PFK showed cross‐reacting material in muscle from both patients. The PFK level in red blood cells, studied in one case, was lower than normal in the patient and both parents. Morphologically, there was extensive deposition of normal glycogen underneath the sarcolemma and in the intermyofibrillar space. In addition, 2% to 3% of the myofibers contained hyaline, PAS‐positive, diastase‐resistant inclusions that had a filamentous fine structure; histochemical reactions suggested an insoluble form of glycogen. Similar inclusions have not been described previously in PFK deficiency. Accumulation of an abnormal polysaccharide in muscle may be due to a second undiscovered enzymatic defect or may be a metabolic consequence of PFK deficiency.
Dominantly inherited peroneal muscular atrophy (hereditary motor and sensory neuropathy type I) in infancy and childhood
Authors: Vanasse M. , Dubowitz V.
Published: January 2005

A detailed clinical and electrodiagnostic study has been undertaken of demyelinating polyneuropathy in 14 children (9 male, 5 female) from 11 sibships and their parents. The onset of symptoms was before the age of 2 years in 12 of the 14 children, and the condition in all cases was nonprogressive or very slowly progressive. In each case one of the parents had a slow motor nerve conduction velocity. Five of the 11 affected parents were completely asymptomatic. Electrodiagnostic studies in both parents of all children with demyelinating peripheral neuropathy are thus important to identify the dominantly inherited form of the disease.
Congenital cervical spinal atrophy
Authors: Darwish Husam , Sarnat Harvey , Archer Carol , Brownell Keith , Kotagal Suresh
Published: January 2005

Three children presented at birth with axial hypotonia and symmetrical flaccid paresis limited to the upper extremities, and involving proximal and distal muscle groups. At birth, palmar flexion creases were poorly developed, and the hand muscles were atrophic. These clinical features, the muscle biopsy findings, and the nonprogressive course, suggest a vascular insult to the cervical spinal cord during gestation. The term, congenital cervical spinal atrophy seems most descriptive of these features.
Inherited canine giant axonal neuropathy
Authors: Duncan Ian D. , Griffiths Ian R. , Carmichael Stewart , Henderson Susan
Published: January 2005

To date, a single case of canine giant axonal neuropathy (GAN) has been recorded. The present report describes the disease in 3 more dogs from the second litter produced by the parents of the original case. Regular clinical and electrophysiological examinations were carried out on all 11 dogs of the second litter. At 14–16 months of age, 3 dogs developed slight posterior ataxia which progressed to a severe lower motor neuron disturbance involving only the hind legs. During this period, each dog began to regurgitate food as a result of megaesophagus. From 12 months of age, there was a progressive reduction in the amplitude of the evoked muscle action potential. Biopsy of the tibial fascicular nerve at 16 months of age confirmed that all 3 dogs had GAN, with numerous swollen unmyelinated fibers and less frequent enlarged myelinated fibers containing accumulated neurofilaments.
Hemiplegic atrophy: Electrophysiological and morphological studies
Authors: Segura Roberto P. , Sahgal Vinod
Published: January 2005

A patient with hemiplegic atrophy following stroke is described. Electrophysiological studies confirmed the absence of root or peripheral nerve involvement. Findings of severe muscle membrane dysfunction and the morphological evidence of lower motor neuron pathology point to a central nervous system process as the origin of the observed changes.
Cross‐reactivity of anti‐acetylcholine receptor autoantibodies
Authors: Garlepp Michael J. H. , Kay Peter H. , Dawkins Roger L. , Bucknall Roger C. , Kemp Andrew
Published: January 2005

The heterogeneity of the specificities of anti‐acetylcholine receptor (anti‐AChR) antibodies of myasthenia gravis (MG) patients has been demonstrated by comparing reactions against a panel of xenogeneic AChR. For each patient there was a more or less unique cross‐reactivity profile. Such heterogeneity emphasizes the need to use human AChR for the routine detection of anti‐AChR. In vitro cross‐reactivity was important in predicting the effect of anti‐AChR after passive transfer to rats. Specificity may influence the outcome in human neonates receiving maternal anti‐AChR via the placenta. In contrast to the extreme heterogeneity seen in spontaneous MG, the antibodies associated with D‐penicillamine–induced MG were more homogeneous.
Clinical study of paramyotonia congenita with and without myotonia in a warm environment
Authors: Haass Anton , Ricker Kenneth , Rüdel Reinhardt , Lehmann‐Horn Frank , Böhlen Reinhard , Dengler Reinhard , Mertens Hans Georg
Published: January 2005

Fourteen patients with paramyotonia congenita were examined clinically. Patients of 3 farnilies had no myotonia in a warm environment while in a cold environment they developed paradoxical myotonia (myotonia aggravated by repeated muscle contraction). Patients of a 4th family had myotonia associated with after‐activity in a warm environment which was not paradoxical. This myotonia was aggravated by cooling. In a warm environment the resting muscles of all patients showed no spontaneous electromyographic activity except for occasional myotonic runs. On cooling, spontaneous fibrillations developed. This was most intense at 32°C–28°C (muscle temperature). On deeper cooling it ceased. In contrast, 5 patients with myotonia congenita did not show such activity during cooling. In all paramyotonic patients cooling (30°C–25°C) produced muscle paralysis, which outlasted rewarming by several hours. At 32°C–30°C muscle relaxation was slowed. Recording of electromyographic activity and isometric contractions of the long finger flexors during cooling revealed that the slowing of muscle relaxation in paramyotonia is not as closely linked to after–activity as is the slowing of muscle relaxation in myotonia congenita.
Membrane defects in paramyotonia congenita with and without myotonia in a warm environment
Authors: Lehmann‐Horn Frank , Rüdel Reinhardt , Dengler Reinhard , Lorković Hrvoje , Haass Anton , Ricker Kenneth
Published: January 2005

Three patients with paramyotonia congenita and 3 control persons were biopsied for an in vitro investigation of the sarcolemmal membrane parameters and of contractile properties of paramyotonic muscle. At 37°C, paramyotonic muscle fibers had normal resting potentials, but on cooling to 27°C they depolarized. Depolarization to –60 mV caused spontaneous activity, and further depolarization to –40 mV caused inexcitability. Depolarization could be prevented by the application of tetrodotoxin, a finding suggesting a defect in the Na channels. Analysis of the membrane current densities using voltage clamps with 3 microelectrodes revealed that in paramyotonic patients at 37°C all component conductances were normal, except for a decreased CI conductance in the patient who had myotonia in a warm environment. At 27°C, the Na and CI conductances were abnormally high. The K conductance was always normal. The results explain the clinical symptoms of weakness and paralysis. Potassium‐ and caffeine‐contracture experiments gave normal results. The clinical symptom of paramyotonic stiffness, therefore, has not been explained by these studies.
Acetylcholine receptor antibodies in myasthenia gravis
Authors: Kornfeld Peter , Nall James , Smith Harry , Mittag Thomas W. , Bender Adam N. , Ambinder Edward P. , Horowitz Steven H. , Papatestas Angelos E. , Gross Harvey , Genkins Gabriel
Published: January 2005

A multivariate statistical analysis of levels of serum acetylcholine receptor antibody (AChR Ab) obtained from 197 patients with various clinical forms of myasthenia gravis (MG) was performed. Elevated AChR Ab levels are specific for MG, but normal AChR Ab levels do not rule out MG. Patients in remission or with purely ocular MG had the lowest incidence of elevation of serum AChR Ab levels, while patients with generalized, severe MG, particularly in the presence of thymoma, tended to have the greatest antibody elevations. Corticosteroids depressed AChR Ab levels, but thymectomy did not exert a consistent effect on antibody levels within a 24‐ to 30‐month postoperative period. The relatively low 55% positivity of antibody elevations in all 197 patients probably reflects the use of heterologous (rat) AChR.
Effect of corticosteroids on the thymus in myasthenia gravis
Authors: Craven Catherine , Reddy P. Krishna , Ringel Steven P. , Rutherford Robert B.
Published: January 2005

The weight and histological appearance of the thymus from patients with myasthenia gravis were studied. Nine patients treated with corticosteroids were compared with 10 patients not treated with corticosteroids before thymectomy. The thymuses of corticosteroid‐treated patients were found to have significantly increased fat and connective tissue, decreased germinal centers, and poorer corticomedullary differentiation than those of untreated patients. The glandular weight and degree of myoepithelial stroma were the same in both groups. The changes following corticosteroid treatment mimic those following aging or acute stress, with retention of the myoepithelial stroma but depletion of thymic lymphoid elements. In myasthenic patients not undergoing thymectomy, the possibility remains that persistent myoepithelial tissue can adversely affect the prognosis.
Surface recording of the H‐reflex of the flexor carpi radialis
Authors: Jabre Joe F.
Published: January 2005

Although the H‐reflex of the triceps surae is used routinely in nerve conduction studies of the lower extremities, doubt still exists concerning the H‐reflex in the upper extremities. The H‐reflex of the flexor carpi radialis is easily obtainable and can be recorded by a simple nerve conduction technique detailed in this communication.
Dynamic aspects of structural proteins in vertebrate skeletal muscle
Authors: Obinata T. , Maruyama K. , Sugita H. , Kohama K. , Ebashi S.
Published: January 2005

In this review, our current knowledge on the structural proteins of vertebrate skeletal muscle is briefly outlined. Structural proteins include the contractile proteins (actin and myosin), the major regulatory proteins (troponin and tropomyosin), the minor regulatory proteins (M‐protein, C‐protein, F‐protein, l‐protein, and actinins), and the scaffold proteins (connectin, desmin, and Z‐protein). In addition, the relative turnover rates of the muscle proteins (M‐protein < troponin > soluble protein as a whole > tropomyosin = α‐actinin > myosin > 10S‐actinin > actin) are discussed. The changes in the turnover of muscle proteins are compared in denervated and dystrophic muscles. The properties of the various proteases in muscle, including alkaline protease, calcium‐activated neutral protease (CANP), and acidic protease (cathepsins), and the structural alterations of myofibrils by these proteases are also described. Finally, the role of proteases and their inhibitors in diseased muscle is summarized, with focus on CANP and its inhibitors, leupeptin and E‐64.
Limb myokymia
Authors: Albers James W. , Allen Arthur A. , Bastron James A. , Daube Jasper R.
Published: January 2005

Thirty‐eight patients with myokymic discharges localized to limb muscles on needle electromyography had various neurologic lesions, both acute and chronic. Of the 38 patients, 27 had had previous radiation therapy and the clinical diagnosis of radiation‐induced plexopathy, myelopathy, or both. For the remaining 11 patients, the diagnoses included multiple sclerosis, inflammatory polyradiculoneuropathy, ischemic neuropathy, inflammatory myopathy, and chronic disorders of the spinal cord and peripheral nerves. The clinical presentations and results of local ischemia, peripheral nerve block, and percutaneous stimulation suggest that most limb myokymic discharges arise focally at the site of a chronic peripheral nerve lesion.
The effects of diltiazem in dystrophic hamsters
Authors: Bhattacharya Syamal K. , Palmieri Genaro M. A. , Bertorini Tulio E. , Nutting David F.
Published: January 2005

Calcium accumulates in muscles of dystrophic hamsters (DH) and patients with Duchenne muscular dystrophy. Various Ca antagonists were beneficial to the cardiomyopathy of DH, but had only minor effects on skeletal muscle. We administered a new Ca antagonist, diltiazem, 25 mg/kg/day orally to normal and dystrophic hamsters from ages 37 to 92 days. We observed a marked reduction in muscle Ca in DH treated with diltiazem: 73% in the heart, 61% in the diaphragm, and 48% in the rectus femoris. Plasma CK was significantly lower (by 37%) in treated DH, while the elevated rate of noncollagen protein synthesis in the diaphragm was not diminished. Histologically, the most important change was a reduction in Ca deposits in the heart. Diltiazem was well‐tolerated by all animals and did not modify Ca content in normal hamsters. This study suggests that diltizem may have therapeutic value in those conditions that are accompanied by excessive accumulation of Ca in tissues, such as muscular dystrophy.
Treatment of ongoing experimental myasthenia gravis with short term high dose cyclophosphamide
Authors: Pestronk Alan , Drachman Daniel B. , Adams Robert N.
Published: January 2005

We have treated animals with an ongoing autoimmune disease, experimental autoimmune myasthenia gravis (EAMG), using a strategy designed to eliminate the antibody‐producing cells. During well‐established EAMG, a single high doese of cyclophosphamide was given because of its known effectiveness against B‐lymphocytes. To counteract the lethal effects of the drug, the rats were “rescued” by bone marrow cell transplantation. This treatment produced a rapid and sustained fall of antibody titers against both the immunizing antigen (Torpedo acetylcholine receptor) and the autoantigen (rat acetylcholine receptor). Immunologic memory, as measured by an anamnestic response to the antigen, was partially suppressed. Cyclophosphamide treatment produced improvement in the neuromuscular defect: treated animals had, on the average, twice as many acetylcholine receptors at neuromuscular junctions compared with untreated EAMG animals. This treatment method of short‐term high doses of an immunosuppressive drug, such as cyclophosphamide, may eventually prove useful for human myasthenia gravis and other autoimmune diseases.
Virological studies in amyotrophic lateral sclerosis
Authors: Kascsak Richard J. , Carp Richard I. , Vilcek Jan T. , Donnenfeld Hyman , Bartfeld Harry
Published: January 2005

Complement‐fixing antibody response to eleven different viruses were measured in amyotrophic lateral sclerosis (ALS) patients, contacts of ALS patients, neurological controls, and normal controls. The normal controls showed a decreased response to adeno‐associated virus and an increased response to adenovirus when compared to the other groups. Levels of interferon‐like substances also were investigated in sera and cerebrospinal fluids of ALS patients and neurological controls. Responses were of a low titer and were not increased in the ALS group. Explant cultures were established from tissues of 24 ALS autopsy cases. Cultures were investigated directly or following fusion to various indicator cell lines for viral‐like agents. Techniques such as interference assays, 5‐bromodeoxyuridine (BudR) induction, hemadsorption, and fluorescent antibody staining failed to detect virus. By addition of helper adenovirus to primary explant cultures, adeno‐associated virus was isolated from 2 of 11 ALS cases.
Age‐related impeded regeneration of mouse minced anterior tibial muscle
Authors: Zacks Sumner I. , Sheff Michael F.
Published: January 2005

The effect of increasing age on the completeness of anterior tibial muscle regeneration from autotransplants of minced muscle has been studied in Swiss Webster and C57/B6J mice aged 18 to 120 days. A progressively declining capability to regenerate new myofibers was associated with a decreasing phagocytic clearance of implanted myofiber debris. Concurrently, there was decreased presumptive myoblast proliferation and new myofiber formation. The importance of age‐related host factors, including nonspecific macrophage activity, in muscle mince regeneration was demonstrated by: (1) the successful regeneration of muscle in hetero‐transplanted muscle minces from older mice implanted in younger animals and (2) the failure of muscle regeneration when the reverse experiment was performed in syngeneic animals. Heterologous striated muscle from the diaphragm regenerated in the bed of the excised anterior tibial muscle, whereas heterologous cardiac muscle failed to regenerate as expected because of the absence of satellite cells. The failure of phagocytic clearance of implanted myofiber mince and concurrent retardation of regeneration suggests a major age‐related nonimmune role of phagocytic macrophages in the early stages of regeneration of anterior tibial muscle from isotopic minced muscle implants.
Giant axonal neuropathy: An inborn error of organization of intermediate filaments
Authors: Pena Sergio D. J.
Published: January 2005

Light microscopic examination of cultured skin fibroblasts from three patients with giant axonal neuropathy (GAN) revealed large aggregates of intermediate filaments (IF). However, electrophoretic analysis of these cells showed normal amounts of vimentin, the fibroblast IF subunit protein. The isoelectric point and peptide mapping of vimentin were identical to controls. Moreover, vimentin was synthesized and phosphorylated at a normal rate. These findings demonstrate that GAN is an inborn error of the organization of IF and suggest that the basic genetic defect in GAN does not involve primarily the IF subunit proteins.
Palmitate oxidation in human muscle: Comparison to CPT and carnitine
Authors: Shumate Jack B. , Carroll James E. , Brooke Michael H. , Choksi Rati M.
Published: January 2005

The evaluation of palmitate oxidation in muscle tissue may be a useful screening test for detecting defects in fatty acid metabolism in human neuromuscular disease. If the test is to be useful, it is necessary to obtain data on a wide variety of muscle illnesses for comparative purposes. We report our experience with palmitate oxidation, muscle carnitine, and carnitine palmityl transferase (CPT) activity in 148 muscle biopsies from a variety of illnesses. The efficacy of using total protein, citrate synthase, and (1‐14C) pyruvate oxidation as internal references was investigated. Palmitate oxidation was significantly less than normal (P ≤ 0.01) in Duchenne muscular dystrophy, congenital nonprogressive myopathy, congenital muscular dystrophy, malignant hyperpyrexia, and denervation, depending on the internal reference used. Muscle carnitine levels followed a similar pattern, however, CPT activity did not. The possibility of these findings being secondary to inactivity is discussed.
Acrylamide neuropathy and changes in the axonal transport and muscular content of the molecular forms of acetylcholinesterase
Authors: Couraud J. Y. , Di Giamberardino L. , Chretien M. , Souyri F. , Fardeau M.
Published: January 2005

Acetylcholinesterase (AChE) is present in nervous and muscular tissues of normal chickens in four main molecular forms (G1, G2, G4, and A12), distinguishable by sedimentation analysis. In the sciatic nerve of acrylamidepoisoned chickens, the anterograde axonal transport of A12 AChE was reduced by 60%, and that of G4 by 21%, compared to control values, whereas the slow axoplasmic transport of G1 and G2 was unaffected. Regarding the leg muscles, only the tibialis anterior revealed dramatic alterations in the distribution of its AChE forms coinciding with a large reduction in the number of nerve endings. In acrylamide poisoning, the AChE molecular forms were considered as very sensitive markers of both axonal transport phases and of the innervation state. Our results support the hypothesis that a defect in the fast axonal transport of proteins might be involved in the degeneration process of the disease.
Unilateral calf enlargement following S1 radiculopathy
Authors: Mielke Ulrich , Ricker Kenneth , Emser Wendelin , Boxler Konstantin
Published: January 2005

Two cases of unilateral calf enlargement following S1 radiculopathy are reported. “True” muscular hypertrophy could be confirmed by computerized tomography of the muscle. Muscle biopsy disclosed that fiber hypertrophy exceeded grouped fiber atrophy. In one case both fiber types were involved, and in the other mostly type 1 fibers were affected. Electromyography revealed dense pseudomyotonic activity and fasciculations. These findings are discussed in view of the current literature.
Lipid composition of sarcoplasmic reticulum from mice with muscular dystrophy
Authors: Mrak Robert E. , Fleischer Sidney
Published: January 2005

We have recently reported on the isolation and characterization of sarcoplasmic reticulum (SR) from normal and dystrophic mice. These purified fractions were similar in functional characteristics. We now present an analysis of the lipids in our purified SR. The lipids were generally found to be similar. Most of the differences found between the two preparations were consistent with a somewhat greater surface membrane contamination in SR fractions from dystrophic mice. This was so with respect to cholesterol content and fatty acid composition. A small decrease, however, in content of phosphatidylcholine was observed in the dystrophic SR fractions. Fluorescence polarization studies using the probe 1,6‐diphenyl‐1,3,5‐hexatriene in sarcoplasmic reticulum membranes over the temperature range 3 to 38 C showed slightly greater anisotropy in the dystrophic fractions, which is also consistent with a greater contamination of this fraction by surface membrane elements (sarcolemma and transverse tubule).
T system abnormalities in differentiating skeletal fibers of dystrophic chickens
Authors: Kidd Parris M. , Yasumura Thomas
Published: January 2005

Ultrastructural T system abnormalities are common in mature skeletal fibers from dystrophic chickens, but little is known of their development. Muscle strips from dystrophic and normal chickens aged 1 day through 4 weeks were examined in ultrathin plastic sections. At hatching, triads were sparse, with no apparent abnormalities. At 1 week, triads were more common; in some dystrophic fibers the T tubules were swollen, ballooned beyond the triad, or assembled asymmetrically, with or without supernumerary (>2) junctional sarcoplasmic reticulum components. At 2 weeks, many dystrophic fibers also displayed degenerative changes, i.e., myofibrillar disintegration and cytoplasmic dispersion. At 4 weeks, when normal triad assembly was complete, T system abnormalities were widespread in dystrophic fibers. Fiber degeneration had progressed to breakdown and replacement. Thus, derangement of the T system (which parallels onset of muscle dysfunction) superimposed on triad assembly suggests that compromised excitation‐contraction coupling is an early event in the chicken dystrophy.
Plasma exchange in chronic inflammatory polyneuropathy: Evidence suggestive of a pathogenic humoral factor
Authors: Toyka Klaus V. , Augspach Regine , Wiethölter Horst , Besinger Uwe A. , Haneveld F. , Liebert Uwe G. , Heininger Kurt , Schwendemann G. , Reiners Karlheinz , Grabensee Bernd
Published: January 2005

Chronic progressive or relapsing inflammatory polyneuropathy (CRIP) can be treated effectively with immunosuppressive drugs and/or plasma exchange (PE). This report describes a patient who responded dramatically and reproducibly to PE during four successive relapses and remained in remission while on medical immunosuppression with azathioprine and corticosteroids. The clinical course was closely correlated with electrophysiologic parameters such as compound muscle action potential amplitudes and distal latencies. The purified lgG fraction of PE filtrate bound to rat and human sciatic nerve on immunohistochemistry. Furthermore, a similar staining pattern was achieved by purified Fab fragments, which was absent in all control preparations. These findings support the hypothesis that circulating plasma factors may play a role in CRIP and that one of these factors may be an IgG antibody to peripheral nerve components.
Inflammatory myopathy: A review of etiologic and pathogenetic factors
Authors: Whitaker John N.
Published: January 2005

Human idiopathic inflammatory myopathy is an acquired disorder with an annual incidence of two to five cases per million. A genetic influence of two to five cases per million. A genetic influence on host susceptibility may also play a role. With the marked heterogeneity of the disease one of the major challenges is to identify subsets that might share a more uniform pathogenesis and manifest a less diverse profile of clinical findings, histopathological abnormalities, and natural history. Dermatomyositis can be distinguished by clinical appearance and pathological changes, but the recognition of additional disease subsets remains very inexact. Current evidence suggests that dermatomyositis occurs as a result of a vasculopathy, but immune mechanisms involved in other categories of idiopathic inflammatory myopathy may also involve cell‐mediated immunity and possibly multiple mechanisms. Even though viral‐induced muscle inflammation occurs in humans, there is no convincing evidence for a viral cause of idiopathic inflammatory myopathy. Experimental allergic myositis may be produced by the injection of animals with skeletal muscle homogenates and complete Freund's adjuvant, but the myositogenic factor is unknown and the parallels between experimental allergic myositis and human idiopathic inflammatory myopathy are limited.
Transient paresis in myotonic syndromes: A simplified electrophysiologic approach
Authors: Streib Erich W. , Sun Sallie F. , Yarkowsky Tony
Published: January 2005

Patients with different myotonic syndromes were evaluated for the presence of transient decrease of muscle fiber excitability. The evoked compound muscle action potential (CMAP) was recorded from the hypothenar eminence; single, supramaximal stimuli were applied to the ulnar nerve at the wrist before and after various periods of voluntary, isometric exercise of the hand muscles. A variable decline of the CMAP after exercise was present in all subjects with myotonia. The results were similar to those obtained with rapid repetitive nerve stimulation.
Myosin light chains in normal and pathological human skeletal muscles
Authors: Pons Françoise , Leger Jocelyne , Georgesco Michel , Bonnel François , Leger Jean J.
Published: January 2005

Thirty‐nine human skeletal muscle biopsies from 24 individuals were classified as normal, neuropathic, or myopathic muscle according to classical clinical observations and histopathological properties of the muscles. The content in myosin light chains (LC) of each muscle sample was analyzed by means of a new technique of polyacrylamide gel electrophoresis that gives an improved discrimination, involving isoelectrofocusing of the muscle homogenate for the first dimension and successive migration in a urea‐containing gel for the second dimension. Four different LC patterns have been observed in the normal muscles; these four patterns and three different ones have been observed in the pathological muscles. No apparent correlation exists between the myosin LC content and the histochemical fiber typing. It is concluded that the myosin LC are apparently not a useful marker to detect the normality or the pathology of human muscle.
The relationship of insulin receptors to hypokalemic periodic paralysis
Authors: Hofmann William W. , Adornato Bruce T. , Reich Harald
Published: January 2005

Single muscle fibers from a typical case of hypokalemic periodic paralysis (HOPP) have been found to be depolarized in all test media and to be cathodally blocked after exposure to insulin. The diseased fibers also bind more insulin and consume more oxygen than controls. The hypothesis proposed is that increased amount or affinity of insulin binding on the HOPP muscles causes continual depolarization in the presence of normally subthreshold concentrations of circulating insulin. This is because of steady effects of the hormone on passive K+ and Na+ fluxes. Additional insulin causes rapid further depolarization with paralysis. Hypokalemia follows if the insulin increment is enough to stimulate active K+ and Na+ transport.
High energy phosphate depletion in a model of defective muscle glycolysis
Authors: Brumback Roger A. , Gerst Jeffery W. , Knull Harvey R.
Published: January 2005

An animal model of defective muscle glycolysis can be produced by intra‐aortic injection of iodoacetate which blocks the glycolytic enzyme glyceraldehyde‐3‐phosphate dehydrogenase. The animals show exercise‐induced, electrically silent muscle cramps and postexercise rhabdomyolysis. Exercised, cramped soleus and extensor digitorum longus muscles from these animals show marked depletion of the high energy compounds adenosine triphosphate (ATP) and creatine phosphate and accumulation of fructose‐1, 6‐diphosphate. This finding supports the hypothesis that exercise‐induced muscle contracture and cell damage in disorders of muscle glycolysis/glycogenolysis are the result of depletion of high energy molecules in the muscle cells.
Stimulation by ACTH4–10 of nerve fiber regeneration following sciatic nerve crush
Authors: Bijlsma Wim A. , Jennekens Frans G. I. , Schotman Peter , Gispen Willem‐Hendrik
Published: January 2005

The number of newly formed myelinated nerve fibers was counted in the sciatic and tibial nerves in the rat following sciatic nerve crush. Beginning at days 8 and 14 in the sciatic and tibial nerve, respectively, the number of new myelinated fibers increased steadily and eventually exceeded the original number by 40 and 30%, respectively. This overshoot in nerve fibers was accompanied by the presence of clusters of fibers. Both the overshoot and the clusters disappeared at later stages and returned gradually to normal values within 3 months. Chronic administration of ACTH4‐10 to the animals resulted in higher numbers of new myelinated nerve fibers throughout the process of regeneration. This stimulation was most pronounced (a three‐fold increase) during the initial stages of regeneration. A higher number of myelinated nerve fibers was also observed in ACTH‐treated rats 60 and 96 days after sciatic nerve crush. No changes in diameter of the fibers could be observed. The results are discussed in terms of a stimulation of the number of outgrowing nerve fibers caused by the peptide treatment.
Two cases of adynamia episodica hereditaria: In vitro investigation of muscle cell membrane and contraction parameters
Authors: Lehmann‐Horn Frank , Rüdel Reinhardt , Ricker Kenneth , Lorković Hrvoje , Dengler Reinhard , Hopf Hanns Christian
Published: January 2005

Membrane potentials, current–voltage relationships, and contractile parameters were studied in intact muscle cell bundles obtained from two patients with adynamia episodica hereditaria. In a normal extracellular medium, the cell membranes had resting potentials of about –80 mV and their current–voltage relationships were not significantly different from control curves. In contrast to normal muscles the afflicted cells were paralyzed in a medium having 6–10 mmol/liter potassium. The mechanisms of paralysis in the two specimens were different from each other. Many fibers from one patient were spontaneously active even in normal solution. In high potassium solution spontaneous activity was increased and the cells gradually depolarized to values at which excitatory sodium current is normally inactivated. This depolarization was connected with an increased sodium conductance and was reversed by the application of tetrodotoxin (TTX). The fibers from the other patient were not spontaneously active. In high potassium solution they were paralyzed at membrane potential values at which normal fibers would still contract. The reason for this paralysis was a reduced excitability.
Myasthenia gravis immunoglobulin augments motor neuron survival without producing muscle paralysis
Authors: Sohal G. S. , Leshner Robert T. , Swift Thomas R.
Published: January 2005

Effects of sera or immunoglobulins from patients with acquired myasthenia gravis on motor neuron survival during critical stages of embryonic development were investigated in the trochlear nucleus–superior oblique muscle system of white Peking duck embryos. A significant increase in motor neuron survival occurred following application of myasthenia gravis sera or myasthenic immunoglobulin during the period of embryonic death of motor neurons. There was no reduction in limb or extraocular muscle movement in treated embryos. Trochlear motor neuron survival persisted after sera or immunoglobulin treatment was discontinued. The total number of muscle fibers and acetylcholine receptros were unchanged following immunoglobulin treatment. Myasthenic immunoglobulin is therefore unique in preventing motor neuron death without producing muscle paralysis and in promoting a prolonged augmentation of motor neuron survival. It is concluded that factors other than muscle activity may also control neuron survival during embryogenesis. Previous studies of myasthenic sera in muscle have shown effects only postsynaptically. This is the first demonstration that myasthenic immunoglobulin affects structures in the central nervous system.
Experimental myasthenia: Lack of correlation between the autoantibody titer and the reduction of acetylcholine‐controlled ionic channels measured at functioning endplates
Authors: Hohlfeld Reinhard , Sterz Raimund , Kalies Inge , Wekerle Hartmut , Peper Klaus
Published: January 2005

Inbred rats with experimental autoimmune myasthenia gravis (EAMG) show no correlation between the serum autoantibody (Antiacetylcholine receptor antibody) concentration and the reduction of endplate acetylcholine‐controlled ionic channels, as measured by a novel electrophysiological technique termed quantitative ionophoresis. This has implications for attempts to explain the well‐documented lack of correlation between the autoantibody titer and the clinical severity of myasthenia gravis (MG).
Spinal muscular atrophy: The natural course of disease
Authors: Russman Barry S. , Melchreit Richard Melchreit , Drennan James C.
Published: January 2005

The infantile form of spinal muscular atrophy (Werdnig‐Hoffmann disease) is thought to be progressive and usually fatal by age three. The intermediate and juvenile forms (Kugelberg‐Welander disease) have been reported to be static in many cases. A review of 48 patients, 50% of whom had been followed for more than 10 years, were placed into four groups according to the maximum motor function attained. Progression of muscle weakness was assessed using functional criteria, including inability to walk, inability to use a manual wheelchair and inability to raise the hands above the head. The results of this analysis suggest that all patients with spinal muscular atrophy have a progressive disease and that the course of the deterioration is predictable in each of the four groups. This information allows one to offer realistic counseling and a rational rehabilitation program.
Physical models of rehabilitation in neuromuscular disease
Authors: Vignos Paul J.
Published: January 2005

Physical methods of treatment for neuromuscular diseases constitute the mainstay of current management. The overall goals of management are the maintenance of independent ambulation and the optimal functional state consistent with the disease process. Maintenance of muscle strength requires regular daily physical activity. An active exercise program can give limited increases of strength in muscular dystrophy dependent on the severity of the disease. Active exercise programs do not result in overwork weakness when properly supervised. Endurance exercise training does not appear to be suitable for Duchenne muscular dystrophy but may have value in the less rapidly progressive neuromuscular diseases. Contracture development can be retarded by passive stretching and splinting initiated early in the disease course. Weight control is important both for ambulatory and wheelchair‐bound patients. Reliable assessment of the results of physical therapy programs has been improved by the introduction of newer, more objective methods for measuring muscle strength.
Fatty acid oxidation intermediates and the effect of fasting on oxidation in red and white skeletal muscle
Authors: Carroll James E. , Villadiego Aida , Morse Daniel P.
Published: January 2005

In vitro oxidation of U‐[14C]glucose‐6‐phosphate, 2‐[14C]pyruvate, and 1‐[14C]pyruvate was significantly reduced in red skeletal muscle from fasting rats. Over the same time interval of fasting, 1‐[14C]palmitate oxidation remained unchanged. Pyruvate dehydrogenase activity, assayed before in vitro activation, was also reduced in red muscle. Long chain acylcarnitine and long chain acyl CoA increased over the same time period in red muscle. Changes in long chain fatty acid derivatives and pyruvate oxidation were much less dramatic in white muscle. We propose that the rise in levels of long chain fatty acid derivatives may be directly related to the inhibition of carbohydrate oxidation during fasting in red skeletal muscle.