bluuebunny/crossref_metadata_2025 huggingface dataset:
The interaction of unregulated actin and myosin in avian muscular dystrophy
Authors: Feit Howard , Farrell Cathy
Published: January 2005

The presence of an altered form of the heavy chain component of myosin subfragment‐1 (S‐1) in avian dystrophic pectoral muscle was confirmed by Triton‐urea‐acetic acid polyacrylamide gel electrophoresis. The potential functional significance of this altered form of S‐1 was evaluated by measuring the ATPase activity of the unregulated acto‐S‐1 complex using all possible pairwise combinations of actin and S‐1 from normal (N) and dystrophic (D) muscle. (NN, DD, ND, DN, where the first letter designates the actin and the second letter the S‐1). With conventionally purified actin and S‐1, NN ≠ DD ≠ ND ≠ DN, implying both N actin ≠ D actin and N S‐1 ≠ D S‐1 functionally. An alternate purification scheme for atin resulted in preparations from normal and dystrophic muscles of actin Mg‐polymers with the same rheology (viscosity vs shear rate) and critical concentration for polymerization. When these actins were combined with more highly purified preparations of S‐1, the adenosine triphosphatase (ATPase) activity of the acto‐S‐1 complex did not vary with changes in the pairwise composition and responded similarly to variation of the actin or adenosine triphosphate (ATP) concentration. In experiments with actin activation of intact myosin, no differences were observed between myosin from normal vs dystrophic muscle. The different isozymes of myosin present in normal and dystrophic chicken pectoral muscles are functionally equivalent as ATPases in their interactions with unregulated actin.
Muscle development in mdx mutant mice
Authors: Dangain Josette , Vrbova Gerta
Published: January 2005

Mechanical and contractile properties of tibialis anterior (TA) muscles from X‐linked muscular dystrophic (mdx) mutant mice at different stages of development are compared to those of muscles from normal control animals. There is no difference between the tension output, speeds of contraction and relaxation, and weight of TA muscles from mutant adults and normal control animals. However, it is found that in 3–4‐week‐old mutant animals, tension output and muscle weight are very much reduced and half relaxation time is prolonged. Thus, during this stage of development, muscles from mdx mice do not function properly. Histological examination of these muscles provides further evidence that, in these animals, rapid muscle destruction occurs at a particular time of development and that it is followed by complete recovery. This new mutant therefore presents an interesting case of muscle destruction and rapid regeneration. However, it is not an adequate model for Duchenne muscular dystrophy.
Granular nuclear inclusion body disease: Fine structure of tibial muscle and sural nerve
Authors: Schröder Johann Michael , Krämer Klaus Günter , Hopf Hanns Christian
Published: January 2005

Fine granular (hyaline) intranuclear inclusion bodies were found in perivascular cells of a muscle and a sural nerve biopsy from a 32‐year‐old woman with slowly progressive motor disturbances. The hyaline nuclear inclusion bodies could be distinguished from other intranuclear hyaline inclusions by their granularity, the size of the granules (approximately 5–15 nm), and the positive iron staining reaction. They were not seen in muscle fibers or Schwann cells. Because of these apparently pathognomonic structural features the patient appears to present a condition that has not been described before.
Passive transfer of the Lambert‐Eaton myasthenic syndrome: Neuromuscular transmission in mice injected with plasma
Authors: Kim Yong I.
Published: January 2005

Mice were given 1 to 67 daily injections of whole plasma from a control subject and a patient with the Lambert‐Eaton myasthenic syndrome (LES), and the parameters of neuromuscular transmission in diaphragm muscles were studied in vitro. In animals that received 41 to 59 injections of LES plasma, mean quantum content of the endplate potentials, as measured under the conditions of low [Ca2+]0 (1.2 mM) and high [Mg2+]0 (10 mM), was reduced to 30% of the control, or 40% of the value found in normal untreated mice. When [K+]0 was elevated from 5 mM to 17.5 mM, the frequency of spontaneous miniature endplate potentials increased by a factor of 98 and 105 respectively in the control and normal mice but only 39 times in the LES plasma recipients. Despite these presynaptic abnormalities, no evidence of postsynaptic deficit, nerve conduction failure, or inability of the muscle fibers to produce normal action potentials was found. These electrophysiologic features in mice thus represent a reproduction of the human condition, supporting the concept of humoral involvement in the pathophysiology of LES. Passively transferred LES in mice is a faithful animal model of the human disease which will be useful in exploring the molecular basis of the presynaptic impairment.
Morphometric anlysis of intramuscular nerves
Authors: Madriaga Evelyn P. , Osame Mitsuhiro , Fukuoka Tadahiro , Sato EiiChi , Gamez Gilberto L. , Igata Akihiro
Published: January 2005

Intramuscular nerves were obtained at autopsy from five adult controls and were morphometrically analyzed. The number of myelinated fibers was directly proportional to the diameter of the fascicles. The fascicles were grouped into six sizes according to diameter. For each group, the normal range of distribution of the number of myelinated fibers could be estimated. Fiber size distribution and myelinated fiber density were also calculated. A unimodal fiber size distribution was observed for the small fascicles (<50m̈m in diameter), and bimodal pattern was observed for the large fascicles. Total myelinated fiber density was high in the small fascicles, and it decreased as the fascicles became larger in size, approaching the values observed In the large peripheral nerves. This study will be helpful in objectively evaluating morphological changes of intramuscular nerves in adult neuromuscular disorders.
Basement membrane component changes in nerve allografts and isografts
Authors: Gulati Adarsh K. , Zalewski Andrew A.
Published: January 2005

This study describes immunocytochemical changes in laminin, which is an integral basement membrane (BM) component, during axonal regeneration through antigenic nerve allografts and nonantigenic nerve isografts. In normal rat nerve, laminin was localized in the BM of Schwann cells and the perineurium. During nerve allograft rejection, the perineurium and Schwann cells disappeared. However, the Schwann cell BMs persisted and became distorted and collapsed. In isografted nerves, the perineurium and Schwann cells were present, and only a few Schwann cell BMs appeared to be distorted; however, the staining for laminin was faint, indicating a possible BM breakdown. A new BM appeared as small rings around the Schwann cells after they had become associated with regenerated axons. Because only a limited axonal regeneration occurred in allografts as compared to isografts, it is concluded that the viable Schwann cells, and their BM architecture, are essential for regeneration through long nerve grafts.
Rabies virus binding to cellular membranes measured by enzyme immunoassay
Authors: Lentz Thomas L. , Chester Janice , Benson Robin J. J. , Hawrot Edward , Tignor Gregory H. , Smith Abigail L.
Published: January 2005

The binding of rabies virus to cellular membranes was measured using an enzyme‐linked immunosorbent assay (ELISA). Virus binding to membranes adsorbed to the wells of microtiter plates was detected with rabies virus antibody and alkaline phosphatase‐linked second antibody. The greatest degree of binding was to myotube, neuroblastoma, and salivary gland membranes; intermediate levels occurred in striated muscle and nerve membranes; and low levels of binding were found in other membranes, including those of most parenchymal organs. Binding of rabies virus to myotube membranes was saturable, dependent on pH (with an optimum of pH 6.0), facilitated by the divalent cations Ca++, Mn++, and Mg++, and was temperature dependent. Binding was greatly reduced by inactivation of virus with β‐propiolactone or treatment of virus with trypsin. In embryonic chick myotubes, total acetylcholine receptor content and acetylcholinesterase activity undergo marked changes during development, first increasing and then decreasing at the time of hatching. Binding of rabies virus followed a similar pattern, indicating that the virus may interact with the acetylcholine receptor or other surface molecules undergoing similar developmental changes.
Contribution of the Na+‐K+ pump to membrane potential in familial periodic paralysis
Authors: Martin A. Robert , Levinson S. Rock
Published: January 2005

The possibility has been raised that in familial periodic paralysis, the relatively large depolarization of the muscle fiber membrane seen during periods of paralysis might be attributable to a reduction in activity of the electrogenic Na+‐K+ pump. The theoretical analysis presented here shows that although such hypotheses are qualitatively correct, the quantitative contribution of the electrogenic pump is too small to account entirely for the changes in membrane potential observed between the paralytic and interictal states.
Surface recording of orthodromic sensory nerve action potentials in median and ulnar nerves in normal subjects
Authors: Andersen Kjeld
Published: January 2005

Reference values of sensory nerve compound action potentials (CAP) were established in 50 healthy subjects by examination with surface electrodes placed in a transverse and a longitudinal position at the wrist. Longitudinal electrodes record potentials of larger amplitude and shorter duration than transversally recorded CAPs. Both amplitude and duration were increased by an increase of interelectrode distance. The use of amplitude and duration as variables is encouraged by the well‐defined biologic variation obtained when fixed interelectrode distance is used and when values are corrected for age and temperature. The strong correlation between amplitude and duration might indicate that the decrease of amplitude with age is caused by the reduction of conduction velocity rather than axonal loss. The ulnar nerve CAPs differ from those of the median nerve mostly with regard to influence of age and temperature. The reasons for this are discussed.
Mononeuropathy multiplex (AAEE case report #11)
Authors: Parry Gareth J. G.
Published: January 2005

Mononeuropathy multiplex is a syndrome of diverse causes, the most common of which is nerve ischemia due to microangiopathy associated with diabetes or the collagen‐vascular diseases. The acquired inflammatory demyelinating neuropathies invariably are multifocal, although the clinical manifestations of these and other multifocal neuropathies may appear symmetrical. The identification of multifocal neuropathies is important because of the frequent therapeutic implications. A case of mononeuropathy multiplex associated with polyarteritis nodosa is described.
Endoneurial injection of antisera to myelin antigens
Authors: Hughes Richard A. C. , Powell Henry C. , Braheny Sherry L. , Brostoff Steven
Published: January 2005

When antisera to purified myelin antigens were injected into rat sciatic nerves, some produced significant demyelination, whereas others merely induced an inflammatory infiltrate. Extensive demyelination was produced by antisera to galactocerebroside and the peripheral nerve glycoprotein P0. Demyelination resulting from injections of antisera to ganglioside GM1, P2, myelin basic protein, sulfatide, and glucocerebroside did not exceed that produced by normal rabbit serum. Addition of guinea pig complement had no effect. It is of interest that the greatest demyelination followed injection of antisera to two molecules, galactocerebroside and P0, the main antigenic determinants of which present at the Schwann cell surface.
The relation between blood lactate and ammonia in ischemic handgrip exercise
Authors: Sinkeler Sytze P. T. , Daanen Hein A. M. , Wevers Ron A. , Oei T. Lian , Joosten Ed M. G. , Binkhorst Rob A.
Published: January 2005

Subjects with myopathies associated with certain enzyme defects often show abnormal concentrations of lactate (LA) and ammonia (NH3) in blood after ischemic exercise. Myoadenylate deaminase (MAD) deficient patients produce only small amounts of NH3, whereas LA rises to normal levels. On the other hand, patients with certain enzyme deficiencies in the glyco(geno)lytic pathway show the opposite. However, the concentrations in blood are dependent on the exercise performed. Standardization of tests for screening purposes, therefore, is necessary. For ischemic contractions, experiments were performed to find the optimal combination for force and frequency, using the highest LA and NH3 concentrations in blood as criteria. Eleven healthy subjects performed ischemic isometric contractions with a handgrip dynamometer at frequencies of 30 and 50/min−1 and force levels of 50%, 65%, and 80% of maximal voluntary contraction (MVC). A combination of 30/min−1 and 80% MVC was found to give the best results.
Mitral valve prolapse in myotonic dystrophy
Authors: Streib Erich W. , Meyers David G. , Sun Sallie F.
Published: January 2005

Forty‐three patients with myotonic dystrophy (MyD) and 43 age‐ and sex‐matched controls were prospectively evaluated for mitral valve prolapse (MVP) using both cardiac auscultation and echocardiography (ECHO). Prevalence of MVP was significantly increased in MyD patients when using either abnormal auscultation plus abnormal ECHO (23.3%, P < 0.02) or abnormal ECHO alone (30%, P < 0.01) as diagnostic criteria for MVP. Frequency of MVP was even more increased in patients with a thin, flat chest compared with patients with normal physical appearance (P < 0.007). These findings are in support of the concept that the increased frequency of MVP in neuromuscular disorders is likely due to geometrical changes of the heart caused by thorax deformities, rather than structural changes of the mitral valve. For this reason, MVP in MyD probably belongs to the entity of so‐called benign, secondary MVP. This is further supported by the absence of symptoms of “systemic” complications of MVP in our patient population.
Postnatal histochemical fiber type differentiation in normal and hypothyroid rat soleus muscle
Authors: Sugie Hideo , Verity M. Anthony
Published: January 2005

We have analyzed the effect of 6‐propylthiouracil‐induced hypothyroidism on neonatal fiber type differentiation in the rat soleus muscle. Body weight, total soleus fiber number, histochemical fiber type differentiation, and morphometry were determined at 7, 14, 21, and 28 days. Neonatal hypothyroidism (1) inhibits the apparent ∼50% increase in soleus muscle fiber number occurring at 14–21 days, (2) blocks the transformation of type 2C to type 2A fibers occurring between 14 and 21 days, (3) preferentially inhibits the increase in type 2 fiber diameter, and (4) retards the development of sarcoplasmic reticulum. Immature muscle fibers reveal type 1 and type 2 fiber myosin adenosine triphosphatase (ATPase) differentiation at pH 10.3, which drops to pH 9.4 with maturation. No myosin ATPase differentiation was found at pH 9.4 in the hypothyroid animals, even at 28 days.
Modified methods for preparation of cryostat sections of skeletal muscle
Authors: Wu Ju‐Sung , Hogan Gwendolyn R. , Morris Jerry D.
Published: January 2005

We developed two modified methods for the preparation of cryostat sections of skeletal muscle: one using solid carbon dioxide and the other using the ultra‐low freezer to prepare 2‐methylbutane (isopentane) for freezing of skeletal muscle. The results were quite satisfactory, with good preservation of cellular details and histochemical properties. Freezing artifacts were minimal when compared with the standard liquid nitrogen method.
Fiber type‐specific autoantibodies in a dog with eosinophilic myositis
Authors: Shelton G. Diane , Cardinet George H. , Bandman Everett , Cuddon Paul
Published: January 2005

Serum from a 2‐year‐old male Belgian sheepdog with eosinophilic myositis, which particularly affects the masticatory muscles, was tested for the presence of muscle‐specific autoantibodies. Control type 2 temporalis muscle fibers were selectively stained following incubation with the patient's serum and staphylococcal protein A conjugated to horseradish peroxidase (SPA‐HRPO). Likewise, type 2 fibers in the patient's temporalis muscle were selectively stained with SPA‐HRPO. The same staining procedures applied to limb muscle did not result in fiber staining. Proteins isolated from the temporalis and triceps brachii muscles of a normal dog were separated under denaturing conditions by onedimensional sodium dodecyl sulfate‐polyacrylamide gel electrophoresis. The separated proteins were transferred onto nitrocellulose paper and incubated with either sera from the patient, normal dogs, or neuromuscular disease controls. Subsequent incubation with peroxidase‐conjugated goat anti‐dog lgG demonstrated antibodies to at least four proteins of the temporalis muscle (myosin heavy chain and three unidentified proteins) when incubated with the patient's serum but not with the controls. Under all conditions, antibodies to the proteins of the triceps brachii were not detected. These findings establish the presence of autoantibodies to specific temporalis muscle proteins that may initiate the myonecrosis and inflammatory response as well as limit the distribution of the response.
Myosin transitions in chronic stimulation do not involve embryonic isozymes
Authors: Hoffman Rebecca K. , Gambke Brigitte , Stephenson Larry W. , Rubinstein Neal A.
Published: January 2005

Chronic low‐frequency stimulation of a fast skeletal muscle effects a transition of myosin isozymes from those characteristic of a fast muscle to those characteristic of a slow muscle. This transformation involves changes in both myosin heavy and light chains. During development, muscles usually change directly from embryonic to neonatal to fast or from embryonic to neonatal to slow isozymes. We have questioned whether chronic stimulation of the adult fast muscle results in a direct fast‐to‐slow isozyme shift or whether transformation requires reexpression of the developmental isozymes prior to the synthesis of adult slow isozymes. We have examined these alternatives in the chronically stimulated dog diaphragm using adenosine triphosphatase (ATPase) histochemistry, pyrophosphate gel electrophoresis of native isozymes, peptide mapping of myosin heavy chains, immunoblotting with an antibody specific to embryonic myosin heavy chain, and solid‐phase radioimmunoassay. We have demonstrated that a transition from adult fast to adult slow isozymes during chronic stimulation does not involve a recapitulation of embryonic isozymes.
A morphological/biochemical study on the actions of corticosteroids on rat skeletal muscle
Authors: Kelly Frank J. , McGrath Josephine A. , Goldspink David F. , Cullen Michael J.
Published: January 2005

Four corticosteroid hormones were administered (5 mg/kg/day) to rats over 6 to 10 days. Both biochemical and microscopic techniques were employed to determine the influence of these corticosteroids on the fine structure and growth of five striated muscles. Throughout, dexamethasone and triamcinalone were more potent than prednisone or cortisone in influencing muscle growth. The corticosteroids' action on the heart was anabolic, increasing its RNA and protein content. In contrast, the same corticosteroids were catabolic against fast‐twitch muscles (e.g., extensor digitorum longus), inducing appreciable atrophy. However, slow‐twitch muscles (e.g., soleus) were more resistant to these hormones, exhibiting an intermediate response between that of the heart and fast‐twitch muscles. Only minor morphological changes were found in both fast and slow muscles 10 days after the corticosteroid treatments. The hormones′ atrophic effects on skeletal muscle primarily arose from the corticosteroid's ability to inhibit protein synthesis, via decreases in the muscles′ ribosomal capacities. Whole‐body protein synthesis was also suppressed by these corticosteroids, but to a lesser extent than in the whole skeletal musculature.
Limitations of the spike‐triggered averaging technique
Authors: Calancie Blair , Bawa Parveen
Published: January 2005

The spike‐triggered averaging technique, when used to obtain the twitch profile of a single motor unit, requires the maintenance by the subject of that unit's minimal rhythmic firing rate, which is typically between 8 and 12 pulses/sec. Literature on the rate—tension relationship of cat motor units shows that some twitches may start to fuse atstimulus rates as low as 2 pulses/sec. This fusion changes the mechanical characteristics of the observed apparent twitch from those of the unfused twitch. The present work has assessed the changes in contraction time, half‐relaxation time, and twitch amplitude of slow versus fast twitch cat single motor units, when these units are demonstrating varying degrees of fusion of tension. As the stimulus rate applied to cat single motor units increased to those typically used during spike‐triggered averaging, the values of all three twitch parameters decreased, with this decrease being more prominent for slow‐contracting versus fast‐contracting units.
Decreased water permeability of erythrocyte membranes in patients with duchenne muscular dystrophy
Authors: Serbu Ana Maria , Marian Alice , Popescu Octavian , Pop Victor I. , Borza Victoria , Benga Ileana , Benga Gheorghe
Published: January 2005

The water proton relaxation times of erythrocytes (T′2a) from 15 Duchenne muscular dystrophy (DMD) patients and age‐matched controls have been determined by a pulse nuclear magnetic resonance technique. Statistically significant higher values of T′2a were noted for the DMD erythrocytes, both in the presence or absence of p‐chloromercuribenzene sulfonate, a potent inhibitor of water diffusion through erythrocyte membrane. As the values of T′2a are inversely related to the water permeability, the results indicate a decreased permeability of erythrocyte membrane in DMD. The findings are discussed in relation to the molecular mechanisms of water diffusion across erythrocyte membrane and in regard to the general problem of membran abnormalities in DMD.
Serum carbonic anhydrase III in myotonic dystrophy
Authors: Mokuno Kenji , Riku Shigeo , Matsuoka Yukihiko , Kato Kanefusa
Published: January 2005

Serum carbonic anhydrase III (CAIII) levels were determined by means of an enzyme immunoassay method and were compared with serum creatine kinase (CK) and muscle‐specific enolase (MSE) levels in 33 patients with myotonic dystrophy. Serum CAIII levels were elevated in all 33 patients, whereas serum CK and MSE levels were elevated in 12 and 10 patients, respectively. Serum CAIII levels showed a good correlation with CK levels, but a poor one with MSE levels. There was no obvious correlation between the serum CAIII level and the duration of illness or the age of the patient. These results suggest that serum CAIII is probably a more sensitive marker than CK and MSE in myotonic dystrophy and may also reflect the type 1 fiber abnormality more predominantly observed in myotonic dystrophy.
Superficial peroneal nerve conduction studies for electromyographic diagnosis
Authors: Levin Kerry H. , Stevens J. Clarke , Daube Jasper R.
Published: January 2005

A new standardized surface technique for conduction studies of the superficial peroneal nerve was developed and applied to 35 normal subjects and 63 patients with peroneal mononeuropathies, lumbar radiculopathies, sciatic neuropathies, lumbosacral plexopathies, or peripheral neuropathies. The response amplitude was greater than 5 μV and the response peak latency was less than 4.1 msec in all normal subjects; however, 8.6% of normal subjects had at least one unelicitable superficial peroneal nerve response (6% of all limbs tested). These data were compared with those of previous studies. Although this technique did not improve the diagnosis of peroneal neuropathy, it did distinguish lumbosacral plexopathy and sciatic neuropathy from L5 radiculopathy and served as a second, easily approachable, sensory conduction study of the leg.
A mathematical analysis of creatine kinase activity in the course of duchenne muscular dystrophy
Authors: Pernice W. , Guggolz M. A. , Guggolz M. , Beckmann R. , Wais U.
Published: January 2005

Recently, clinical follow‐up studies have shown that the age of first symptoms and the speed of progress may vary considerably in Duchenne muscular dystrophy (DMD). Prognostic factors would be of interest not only for the patients themselves, but also for the selection of DMD patients for therapeutic studies. Creatine kinase (CK) activity reflects the dystrophic degeneration of the muscle cells. Therefore, the coherence of the course of CK activity and its relationship to the clinical state was investigated with the aid of a heuristic mathetmatical formula. Two constants were calculated, b and c The data of 88 DMD patients proved the validity of the mathematical formula. Constant b seemed to be of no clinical relevance. The height of constant c was related to the age at which the ability to walk was lost (r = −0.76). This constant provides an objective individual assessment of the prognosis in DMD. In addition, the mathematical analysis of the CK course opens the way for a prospective CK estimation, which is relevant for the evaluation of therapeutic trials.
Muscle membrane excitation and impulse propagation velocity are reduced during muscle fatigue
Authors: Milner‐Brown H. S. , Miller Robert G.
Published: January 2005

In order to determine whether or not impulse propagation was impaired during muscle fatigue, evoked muscle compound potentials (MCP) and twitches were recorded, both before and after fatigue, from the first dorsal interosseus (FDI), adductor pollicis (AP), and anterior tibialis (AT) muscles following supramaximal ulnar and peroneal nerve stimulation, respectively. The muscles were fatigued by maintaining maximum voluntary isometric, index finger abduction, thumb adduction, or ankle dorsiflexion for 1–5 minutes. FDI was most markedly altered, with reduced MCP amplitude (mean 32%) and increased MCP duration (mean 47%) after only 1 minute. After fatigue of longer duration (3–5 minutes), there were corresponding reductions in both the MCP amplitudes and the twitch tensions recorded from both the FDI and ankle dorsiflexors. We conclude that (1) a reduction in both the level of excitation and impulse propagation velocity of muscle membranes occurs during muscle fatigue, and (2) the magnitude of this reduced membrane function and its contribution to the mechanisms underlying fatigue depend both on the duration and degree of fatigue, as well as on the intrinsic properties of the particular muscle.
Simulation and analysis of the electromyographic interference pattern in normal muscle. Part I: Turns and amplitude measurements
Authors: Nandedkar Sanjeev D. , Sanders Donald B. , Stålberg Erik V.
Published: January 2005

The electromyographic (EMG) interference pattern (IP) was simulated by adding together motor unit action potentials (MUAPs) of different sizes that had been recorded by a concentric needle EMG electrode. The number of turns (NT) of the simulated IP increased with the number of MUAP discharges. The mean amplitude (MA) difference between successive turns in the IP increased when large amplitude MUAPs were added. Our analysis demonstrates that the MA of the IP is determined mainly by the amplitude of large MUAPs in the signal and that large amplitude spikes are more likely to be generated by single large amplitude MUAPs than by summation of several small amplitude MUAPs.
Endoneurial sodium accumulation in galactosemic rat nerves
Authors: Mizisin Andrew P. , Myers Robert R. , Powell Henry C.
Published: January 2005

Microdrop samples of endoneurial fluid and serum from galactosemic rats were analyzed with energy dispersive spectrometry (EDS). The sodium concentration of endoneurial fluid from galactose‐fed rats (295 meq/liter) was nearly twice that of age‐matched controls (152 meq/liter) and indicates that sodium is present in an osmotically significant concentration that is capable of causing the edema and increased endoneurial fluid pressure (EFP) associated with galactose neuropathy. It is suggested that accumulation of endoneurial sodium is linked to the movement of sugar into the endoneurium.
Facioscapulohumeral muscular dystrophy: The choice of a biopsy site
Authors: Bodensteiner John B. , Schochet Sydney S.
Published: January 2005

The utilization of so‐called standard muscles for biopsy in patients with the clinical features of facioscapulohumeral muscular dystrophy (FSH) often results in nondiagnostic pathologic findings. Five patients are presented who had biopsies of the supraspinatus muscle in addition to one of the standard muscles. The supraspinatus muscle was diagnostic in all five cases. The findings suggest that the supraspinatus muscle should be considered as the biopsy site of first choice in those patients in whom the clinical picture suggests facioscapulohumeral‐type muscular dystrophy.
Role of glucocorticoids in the response of rat leg muscles to reduced activity
Authors: Jaspers Stephen R. , Tischler Marc E.
Published: January 2005

Adrenalectomy did not prevent atrophy of rat soleus muscle during 6 days of tail cast suspension. Cortisol treatment enhanced this atrophy and caused atrophy of the weight‐bearing soleus and both extensor digitorum longus (EDL) muscles. Unloading led to increased sarcoplasmic protein concentration in the soleus, but cortisol administration increased the myofibrillar (+stromal) protein concentration in both muscles. Suspension of hindlimbs of adrenalectomized animals led to faster protein degradation, slower sarcoplasmic protein synthesis, and faster myofibrillar protein synthesis in the isolated soleus, whereas with cortisol‐treated animals, the difference in synthesis of myofibrillar proteins was enhanced and that of sarcoplasmic proteins was abolished. Both soleus and EDL of suspended, cortisol‐treated animals showed faster protein degradation. It is unlikely that any elevation in circulating glucocorticoids was solely responsible for atrophy of the soleus in this model, but catabolic amounts of glucocorticoids could alter the response of muscle to unloading.
Ionic channels: I. The biophysical basis for ion passage and channel gating
Authors: Ruff Robert L.
Published: January 2005

This article reviews the biophysics of ion passage through membrane pores, as well as the physical factors that control the ion selectivity, gating, and conductance of an ionic channel. Different voltage clamp techniques are discussed in detail. The biophysical properties of sodium channels are reviewed.
Electrophysiologic denervation changes of human muscle fibers in motoneuron diseases
Authors: Uchitel Osvaldo D. , Dubrovsky Alberto L.
Published: January 2005

Muscle denervation and reinnervation by sprouting of the surviving motoneurons characterizes diseases (MND). In mammalian muscles, experimental denervation induces the appearance of extrajunctional acetylcholine (ACh) receptors and tetrodotoxin (TTX) resistant action potentials (AP). These denervation changes have been investigated in muscle biopsies from 10 MND patients and in 2 traumatically denervaed normal human muscles. Extrajunctional ACh sensitivity was present in 113 of the 140 (73%) fibers from MND muscles studied. In 50 of 84 (70%) ACh‐sensitive fibers, no TTX‐resistant AP were present. The remaining fibers (30%) showed small regenerative responses. In contrast, all the traumatically denervatedmuscle fibers showed extrajunctional ACh sensitivity and TTX‐resistant AP. Histochemical analysis of the biopsies showed no direct correlation between the frequency of ACh‐sensitive fibers and that of the atrophic or normal‐appearing fibers. The absence of TTX‐resistant AP in ACh‐sensitive fibers and its lack of correlation with the histochemical criteria of denervation suggest the presence of a state of innervation in MMD, where the motoneuron is not able to maintain its fully trophic influence on the muscle fiber membrane.
Creatine kinase isoforms following isometric exercise
Authors: Clarkson Priscilla M. , Apple Fred S. , Byrnes William C. , McCormick Kathleen M. , Triffletti Philip
Published: January 2005

The present study assessed creatine kinase (CK) activity, CK MM isoforms, and muscle soreness following an exercise regimen designed to induce skeletal muscle damage. Eight college‐age subjects performed 40 maximal isometric contractions of the knee extensor muscles (10‐second contraction/20‐second rest). Serum samples and soreness ratings were taken prior to and 2, 6, 18, and 24 hours after the exercise. The CK MM1 and CK MM3 isoforms were determined by flatbed isoelectric focusing (IEF). In serum, the MM1 isoform (the pure gene product) is considered to be evidence of newly released CK from muscle, as upon entering the plasma, the CK MM1 is converted to MM2 and then MM3. A significant increase in serum CK activity was found at 6 hours and remained elevated at 24 hours. CK MM1 increased significantly at 2 hours, peaked at 6 hours, then approached baseline. Soreness did not increase significantly until 18 hours. Analysis of CK isoforms in serum can provide an earlier indicator of skeletal muscle damage than total CK or perception of soreness and may be useful in tracking the time course of skeletal muscle damage and repair.
The effect of isometric short‐term electrical stimulation on denervated muscle
Authors: Nix Wilfred A. , Dahm M.
Published: January 2005

Electrical stimulation was applied daily for 20 minutes to denervated rabbit extensor digitorum longus muscle. One group was stimulated with short tetani, another with 1‐Hz frequency, using isometric contractions for both. Tetanic stimulation induced severe fibrosis and is harmful to denervated muscle. One Hertz stimulation retarded denervation‐induced fatigue and atrophy, as well as slowing of contraction time.
Management of end stage respiratory failure in duchenne muscular dystrophy
Authors: Bach John R. , O'Brien John , Krotenberg Robert , Alba August S.
Published: January 2005

There were 31 Duchenne patients placed on overnight mouth intermittent positive pressure ventilation for severe respiratory insufficiency at the average age of 19.9 years. Most patients had vital capacities less than 200 cc at their last evaluations. Of these, 23 patients are alive at the average age of 27 years and live in the community, although they are dependent on assisted ventilation 24 hours a day. There were 8 patients who died at the average age of 30 years. Although normocapnic during the day, the presence of symptomatic nocturnal hypoventilation or pCO2 over 55 mmHg documented by continuous overnight capnograph study indicates the need for introducing overnight respiratory assistance. Mouth intermittent positive pressure ventilation alone or in combination with other techniques of ventilatory assistance can prolong life while allowing optimal function, attainment of higher levels of education, and home management of patients with Duchenne muscular dystrophy.
Molecular analysis of human muscular dystrophies
Authors: Davies K. E. , Forrest S. , Smith T. , Kenwrick S. , Ball S. , Dorkins H. , Patterson M.
Published: January 2005

The ability to map disease loci using restriction fragment legth polymorphisms (RFLPs) identified by DNA probes has revolutionized molecular genetics. Duchenne and Becker muscular dystrophies have been shown to be localized within the same very small region of Xp21 on the human X chromosome. The mutation itself should soon be identified at the DNA level, which will permit a detailed analysis of the molecular defect at the biochemical level. Rapid progress has also been made in the study of myotonic dystrophy on chromosome 19. DNA markers closely linked to the mutant locus have been identified, making antenatal diagnosis possible in informative families. Autosomal recessive muscular dystrophies are more difficult to study, but the means to localize even these mutations is being developed. The next decade shold prove to be an exciting one for those involved in the molecular analysis and clinical management of human muscular dystrophies.
The pattern of involvement of adult‐onset acid maltase deficiency at autopsy
Authors: van der Walt Jon D. , Swash Michael , Leake Janet , Cox Elaine L.
Published: January 2005

The autopsy findings in a clinically and biochemically documented case of adult‐onset acid maltase deficiency presenting with limb girdle myopathy are presented. The skeletal muscles, tongue, extraocular and smooth muscles of gut and arterioles showed a vacuolar myopathy, most severely affecting proximal skeletal muscles. Muscle spindles were severely affected in all muscles. The heart showed basophilic degeneration and a vacuolar myopathy. The visceral organs and nervous system were morphologically normal. Possible mechanisms for this differential involvement of muscles and tissues are discussed.
Repeated stimulation of the dystrophic mouse neuromuscular junctions
Authors: Tremblay Jacques P. , Grégoire Laurent , Sasseville Rachelle , Belhumeur Celine
Published: January 2005

Morphometric changes produced by repeated stimulation of the neuromuscular junctions (NMJs) have been studied by electron microscopy in 769 profiles of normal, heterozygous dystrophic, and dystrophic mice. The study indicates that in animals not stimulated but anesthetized for 40 min, there is no significant difference in the profile area between the normal, the heterozygous dystrophic, and dystrophic mice. There is also no significant difference between these three groups in the number of clear vesicles and of coated vesicles per m̈m2 of terminal. Following stimulation, the profile area of NMJs is not significantly increased in the normal and in the heterozygous dystrophic mice. However, the profile area is increased by 50% in the dystrophic animals. This is perhaps due to changes in the shape of the nerve terminal in stimulated dystrophic animals. However, the number of the clear vesicles per m̈m2 is significantly reduced to a similar extent in the three groups. These results indicate that the recycling of vesicular membrane is normal in dystrophic animals.
Frequency of bifurcated muscle fibers in hyperthrophic rat soleus muscle
Authors: Snow Mikel H. , Chortkoff Ben S.
Published: January 2005

The total number of bifurcated and nonbifurcated fibers were counted in rat soleus muscles induced to hypertrophy by surgical ablation of the gastrocnemius and plantaris muscles. Sham‐operated and normal soleus muscles served as controls. Every muscle fiber within the entire muscle was individually examined and counted with the aid of a dissecting microscope following a 10–12 hour nitric acid digestion of the connective tissue. The results show that the total number of muscle fibers in the hypertrophic soleus did not differ significantly from the control. The frequency of bifurcated fibers observed in the control muscles was significantly greater than has been previously reported, and their frequency in the hypertrophic muscles, although slightly increased, was not significantly different from control values. These data confirm that fiber hypertrophy is not accompanied by hyperplasia, and they further suggest that bifurcated fibers probably play an insignificant role during muscle adaptation to hypertrophy due to their very low frequency.
Adynamia episodica hereditaria with myotonia: A non‐inactivating sodium current and the effect of extracellular pH
Authors: Lehmann‐Horn Frank , Küther Gerald , Ricker Kenneth , Grafe Peter , Ballanyi Klaus , Rüdel Reinhardt
Published: January 2005

To study the mechanism of periodic paralysis, we investigated the properties of intact muscle fibers biopsied from a patient who had adynamia episodica hereditaria with electromyographic signs of myotonia. When the potassium concentration in the extracellular medium, [K]e, was 3.5 mmol/l, force of contraction, membrane resting potential, and intracellular sodium activity were normal, but depolarizing voltage clamp steps revealed the existence of an abnormal inward current. This current was activated at membrane potentials less negative than −80 mV, reached a maximum within 50 msec, and was not inactivated with time. The inward current was completely and reversibly blocked by tetrodotoxin, which indicates that it was carried by sodium ions. In a solution containing 9 mmol/l potassium, normal muscle would depolarize to −63 mV and yet be capable of developing full tetanic force upon stimulation. The muscle from the patient depolarized to −57 mV and became inexcitable, i.e., it was paralyzed. A contracture did not develop. Lowering of the extracellular pH did not influence the resting potential, but it effectively antagonized or prevented the paralytic effect of high [K]e by changing the inactivation characteristics of the sodium channels. Hydrochlorothiazide, which had a therapeutic effect on the patient, did not prevent paralysis in vitro. An abnormal rise of the intracellular sodium activity was recorded when the extracellular potassium concentration was raised to 10 mmol/l.
The effect of DDB on dystrophic hamsters: An in vivo and in vitro study
Authors: Shen Ding‐Guo , Araki Makoto , Higuchi Itsuro , Matsumoto Kazuko , Tamai Masaharu , Liu Keng‐Tao , Sugita Hideo
Published: January 2005

Dimethl‐4, 47′‐dimetoxy‐5, 6, 5′–6′‐dimethylenedioxybiphenyl‐2, 2′‐dicarboxylate (DDB) is a synthetic analogue of Schizandrin C, an active compound isolated from a Chinese herb, Fructus schizandrae. We administered this compound to dystrophic hamsters in vivo for 31 days. This led to a 61% reduction of the calcium content, a 86% reduction of the area of calcium deposits, and a 52% reduction of the area of necrosis of cardiac muscle. However, skeletal muscle necrosis was not significantly improved. No clear change in plasma creatine kinase (CK) was observed. In an in vitro incubation study, the rate of CK release and tetanus tension of the extensor digitorum longus muscle of dystrophic hamsters were not substantially changed by the addition of DDB. This study suggests that DDB has some effect on cardiac necrosis, and that it might be useful for treatment of the cardiac involvement in patients with muscular dystrophy or other conditions with accompaning Ca accumulation.
Effect of spinal cord TRH deficiency on lower motorneuron function in the rat
Authors: van den Bergh Peter , Kelly John J. , Adelman Lester , Munsat Theodore L. , Jackson Ivor M. D. , Lechan Ronald M.
Published: January 2005

Thyrotropin‐releasing hormone (TRH), present in high concentrations in the mammalian spinal cord, exerts excitatory effects on the alpha‐motorneuron (AMN) via axodendritic contacts. We used the neurotoxin 5,7‐dihydroxytryptamine (5,7‐DHT) to deplete TRH from the ventral horn of the spinal cord of adults rats to determine whether the tripeptide may be trophic to the AMN. The rats were studied blindly and sequentially for 11 weeks. Motor performance remained normal by clinical and electrophysiologic assessments. AMN counts were not reduced in the lumbar cord, and gastrocnemius muscle showed no evidence of denervation in treated rats. We conclude that in the adult rat chronic ventral horn TRH deficiency does not lead to AMN degeneration and is not associated with a significant alteration of AMN function.
Increased serum myosin light chain 3 level in neuromuscular diseases
Authors: Konagaya Mosaaki , Konagaya Yoko , Horikawa Hirosei , Takayanagi Tetsuya
Published: January 2005

A radioimmunoassay for human skeletal muscle myosin light chain 3 (MLC‐3) was developed. The serum level of MLC‐3 was evaluated in 143 patients suffering from neuromuscular diseases. Increased MLC‐3 level was observed in muscular dystrophies. There were significant positive correlations between serum levels of MLC‐3 and creatin kinase (CK) in Duchenne and limb‐girdle type muscular dystrophy, but the regression lines were different. Patients with neurogenic amyotrophy, especially amyotrophic lateral sclerosis, also showed elevated MLC‐3 levels with or without high CK, and the frequency of increase in MLC‐3 was greater than that of CK. The results of the present study suggest that circulating MLC might be a useful marker for muscle breakdown not merely in myopathies but in neurogenic disorders.
Experimental investigation of muscular neurotization in the rat
Authors: Must Rachel
Published: January 2005

Reinnervation of a free muscle graft by nerves from an adjacent intact muscle is called muscular neurotization. This paper investigates the mechanisms and stimuli responsible for muscular neurotization in the rat. Sternohyoid or sternomastoid muscles were transplanted as free muscle grafts to the ventral surface of an intact sternohyoid muscle (feeder muscle). After several weeks the graft and underlying feeder muscle were removed together, frozen, serially sectioned, stained, and carefully examined for the presence or absence of nerves. It was concluded from a series of experiments that in this model muscular neurotization is a form of nerve regeneration. In order for muscular neurotization to occur, it is necessary to have (1) injury to the nerves of the intact feeder muscle and (2) a pathway upon which the regenerating nerves may grow into the graft.
Enhanced release of ammonia and hypoxanthine from exercising muscles in patients with idiopathic hypoparathyroidism
Authors: Hara Naoko , Mineo Ikuo , Kono Norio , Shimizu Takao , Yamada Yuya , Kawachi Masanori , Suzuki Koyasu , Fukumoto Yasuaki , Tarui Seiichiro
Published: January 2005

Semiischemic forearm exercise tests were carried out in two patients with idiopathic hypoparathyroidism who had muscle cramps and high serum levels of creatine kinase. Although cubital venous lactate levels increased normally after forearm exercise, venous ammonia and hypoxanthine were greatly increased. The abnormal responses of ammonia and hypoxanthine were normalized 3 months after treatment with 1 α‐hydroxyvitamin D3. These findings suggest that excess purine degradation occurred in exercising muscles of patients with idiopathic hypoparathyroidism.
Decreased plasmalogen ratios in cultured skin fibroblasts from myotonic dystrophy
Authors: Sakai Tetsuo , Antoku Yasunobu
Published: January 2005

It has become known that hypolipidemic agents, which can induce experimental myotonia in humans and animals, may alter the lipid metabolism of intracellular organelles, peroxisomes. However, there has been no reported study on peroxisomal lipid metabolisms in myotonic dystrophy showing myotonia as well as experimental myotonia. We investigated one of the peroxisomal lipid metabolisms, i.e., plasmalogen metabolism in cultured skin fibroblasts from myotonic dystrophy, and found plasmalogen ratios to be significantly reduced.
Membrane defects in paramyotonia congenita (eulenburg)
Authors: Lehmann‐Horn Frank , Rüdel Reinhardt , Ricker Kenneth
Published: January 2005

Membrane potentials, current‐voltage relationships, and component conductances were determined in resting excised external intercostal muscle fibers from five patients with paramyotonia congenita. At 37°C all investigated parameters were normal. At 27°C the resting potentials decreased to about −40 mV, and the fibers were inexcitable. At this stage the membrane currents were much larger than in normal fibers owing to increases in the membrane conductances for Na and Cl ions. The earlier finding that in the cold the Na permeability is abnormally large was confirmed. The Cl permeability was shown to be normal even in the cold. The decrease of the resting potential and the changes in the current‐voltage relationship at 27°C could be prevented by the use of the Na channel blocker tetrodotoxin (TTX) or by bathing the fibers in a Na‐free solution. Our previous conclusion that the Cl conductance at 27°C was also increased when TTX was present was not confirmed. Exposure of a muscle bundle to 7 mmol/l potassium did not lead to excessive depolarization and paralysis.