Monoamine oxidase activity in normal and dystrophic human muscle

Monoamine oxidase activity was determined in skeletal muscles of normal subjects and patients with Duchenne muscular dystrophy, other major forms of muscular dystrophies and certain related diseases. The activity was found to be unaltered in all diseases that were examined.     

Sodium Channel and Sodium Pump in Normal and Pathological Muscles from Patients with Myotonic Muscular Dystrophy and Lower Motor Neuron Impairment

TWO SODIUM TRANSPORT SYSTEMS HAVE BEEN ANALYZED IN THIS WORK: the voltage-sensitive sodium channel and the (Na(+), K(+)) ATPase pump. The sodium channel has been studied using a tritiated derivative of tetrodotoxin; the sodium pump has been studied using tritiated ouabain. Properties of interaction of tritiated tetrodotoxin and of tritiated ouabain with their respective receptors were observed in normal human skeletal muscle and in muscles of patients with myotonic muscular dystrophy and with lower motor neuron impairment.Levels of sodium pump and of sodium channels were measured at different stages of membrane purification. Microsomal fractions of normal human muscle have maximal binding capacities for tetrodotoxin of 230 fmol/mg of protein and of 7.4 pmol/mg of protein for ouabain.Dissociation constant for the complexes formed by the tetrodotoxin derivative and by ouabain with their respective receptors were 0.52 nM and 0.55 muM, respectively.In muscles from patients with myotonic muscular dystrophy, the maximal binding capacity for tetrodotoxin, i.e., the number of Na(+) channels was found to be very similar to that found for normal muscle. The maximal binding capacity for ouabain, i.e., the number of Na(+) pumps was three- to sixfold lower than in normal muscle. Dissociation constants for the complexes formed with the tetrodotoxin derivative and with ouabain were the same as for normal muscle.In muscles from patients with lower motor nerve impairment, the maximal binding capacities for tetrodotoxin and for ouabain were twice as high as in normal muscle. Again, dissociation constants for the complexes formed with the tetrodotoxin derivative and with ouabain were nearly unchanged as compared with normal muscle.These results suggest that sodium transport systems involved in the generation of action potentials and/or in the regulation of the resting potential are altered both in myotonic muscular dystrophy and in lower motor neuron impairment.     

良性假肥大型肌营养不良症患者肺功能的表现特点与康复对策

目的：探讨良性假肥大型肌营养不良症（BMD）患者的肺功能表现特点与康复对策。方法：测定12例BMD患者的肺通气功能并将数据进行统计学处理。分析其临床表现。结果：12例患者的肺通气功能主要指标均值均在正常范围，但1s用力呼气容积与用力肺活量之比值（FEV1／FVC）较正常人群明显增高。结论：FEV1／FVC比例不协调是BMD患者肺通气功能的主要特点，其原因可能与呼吸肌尤其是主要吸气肌膈肌和主要辅助呼气肌腹肌肌力较弱有关，康复锻炼对改善FEV1，／FVC比例的不协调有帮助，应列为BMD患者必做的康复训练。     

Muscle transketolase in normal foetuses and Duchenne dystrophy

The activity of the enzyme transketolase (EC 2.2.1.1) or the pentose phosphate metabolizing enzyme (PPME) was investigated in the quadriceps muscles of patients with Duchenne muscular dystrophy (DMD), polymyositis and spinal muscular atrophy (SMA) and in normal foetuses. The enzyme activity was significantly elevated in these muscle disorders with highest and lowest levels seen in DMD and SMA groups, respectively. The enzyme activity was increased early in DMD muscle and appeared to increase with progression of the disease. Normal foetal muscle contained high transketolase activity which is comparable to that seen in DMD patients.     

Aminoglycoside antibiotics restore dystrophin function to skeletal muscles of mdx mice

Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene, leading to the absence of the dystrophin protein in striated muscle. A significant number of these mutations are premature stop codons. On the basis of the observation that aminoglycoside treatment can suppress stop codons in cultured cells, we tested the effect of gentamicin on cultured muscle cells from the mdx mouse - an animal model for DMD that possesses a premature stop codon in the dystrophin gene. Exposure of mdx myotubes to gentamicin led to the expression and localization of dystrophin to the cell membrane. We then evaluated the effects of differing dosages of gentamicin on expression and functional protection of the muscles of mdx mice. We identified a treatment regimen that resulted in the presence of dystrophin in the cell membrane in all striated muscles examined and that provided functional protection against muscular injury. To our knowledge, our results are the first to demonstrate that aminoglycosides can suppress stop codons not only in vitro but also in vivo. Furthermore, these results raise the possibility of a novel treatment regimen for muscular dystrophy and other diseases caused by premature stop codon mutations. This treatment could prove effective in up to 15% of patients with DMD.     

神经源性肌萎缩的MRI表现

目的：探讨神经源性肌萎缩的病变肌肉的MRI表现及MRI的应用价值。材料和方法：选择30例经临床证实的神经源性肌萎缩患者，选择舌头、肩胛肌带、大腿及双侧手掌行MRI检查。结果：①肌萎缩侧索硬化症者15例，其中舌肌萎缩4例；手掌蚓状肌及骨间肌萎缩6例，受累肌肉见斑片状长T2等T1异常信号影；双侧大腿肌肉见片状混杂信号影1例；4例表现为双侧手掌肌肉萎缩，信号无异常。余受检部位肌肉形态及信号无明显异常。②脊肌萎缩症1例，腓骨肌萎缩症2例，均表现双下肢肌肉萎缩，肌肉内见短T1长T2异常信号。③平山病8例，表现受累肌肉萎缩，手掌蚓状肌及骨间肌见斑片状长T2等T1异常信号影；④4例为单侧下肢的神经源性肌萎缩，表现为肌肉萎缩，肌肉内可见斑片状长T2及短T1混杂信号影。结论：神经源性肌萎缩主要表现为病变区肌肉的萎缩，部分肌肉为脂肪替代，另有部分病变肌肉可表现为肌纤维的坏死性改变。     

Cardiac troponin I and troponin T: recent players in the field of myocardial markers.

The troponin (Tn) complex consists of three subunits referred to as TnT, TnI and TnC. Myocardium contains TnT and TnI isoforms which are not present in skeletal muscles and which can be separated from the muscular isoforms by immunological techniques. Using commercially available immunoassays, clinical laboratories are able to determine cardiac TnT and TnI (cTnT and cTnI) quickly and reliably as classical cardiac markers. After acute myocardial infarction, cTnT and cTnI concentrations start to increase in serum in a rather similar way than CK-MB, but return to normal after longer periods of time (approximately one week). Because of their excellent cardiac specificity, Tn subunits appear ideally suited for the differential diagnosis of myocardial and muscular damage, for example in noncardiac surgery patients, in patients with muscular trauma or with chronic muscular diseases, or after intense physical exercise. cTnT and cTnI may also be used for detecting evidence of minor myocardial damage: therefore they have found new clinical applications, in particular risk stratification in patients with unstable angina. In spite of the possible reexpression of cTnT in human skeletal muscles, and of the lack of standardization of cTnI assays, Tn subunits are not far to meet the criteria of ideal markers for acute myocardial injury. Only an insufficient sensitivity in the first hours following the acute coronary syndroms requiries to maintain an early myocardial marker in the cardiac panel for routine laboratory testing.     

Glyoxalase enzyme system in human muscular dystrophy.

Glyoxalase I and glyoxalase II activities were determined in skeletal muscle of control subjects and of patients with Duchenne dystrophy, other major forms of muscular dystrophies and certain neuromuscular disorders. The glyoxalase I activity was normal in all diseases examined except in Duchenne and limb girdle types of muscular dystrophy, where it showed a significant moderate decrease. The glyoxalase II activity in normal human muscle was very low, and the activity was unaltered in muscle of patients with Duchenne and other major forms of muscular dystrophies and spinal muscular atrophy. The selective decrease of glyoxalase I activity in recessively inherited muscular dystrophies may have some relevance to some phases of these disease processes.     

Muscle Ultrasound Changes Correlate With Functional Impairment in Spinal Muscular Atrophy

ObjectiveWe investigated ultrasound patterns of muscle involvement in different types of spinal muscular atrophy (SMA) and their correlation with functional status to determine the pattern of muscle compromise in patients with SMA and the potential role of ultrasound to evaluate disease progression.MethodsWe examined muscles (biceps brachii, rectus femoris, diaphragm, intercostals and thoracic multifidus) of 41 patients with SMA (types 1 to 4) and 46 healthy age- and sex-matched control individuals using B-mode ultrasound for gray-scale analysis (GSA), area (biceps brachii and rectus femoris) and diaphragm thickening ratio. Functional scales were applied to patients only. We analyzed ultrasound abnormalities in specific clinical subtypes and correlated findings with functional status.ResultsCompared with controls, patients had reduced muscle area and increased mean GSA for all muscles (p < 0.001), with an established correlation between the increase in GSA and the severity of SMA for biceps brachii, rectus femoris and intercostals (p = 0.03, 0.01 and 0.004 respectively) when using the Hammersmith Functional Motor Scale Expanded. Diaphragm thickening ratio was normal in the majority of patients, and intercostal muscles had higher GSA than diaphragm in relation to the controls.ConclusionUltrasound is useful for quantifying muscular changes in SMA and correlates with functional status. Diaphragm thickening ratio can be normal even with severe compromise of respiratory muscles in quantitative analysis, and intercostal muscles were more affected than diaphragm.     

Ultrasonography in the evaluation of muscular trauma.

Ultrasonography was performed to assess muscle injuries in 120 advanced-level athletes. Real-time sonography was chosen for evaluation since it allowed a comparison between the muscles at rest and during contraction. Pathologic patterns are reported and compared with the normal ultrasonic muscular anatomy. Twenty-five subjects were referred for surgery. All lesions had abnormal sonograms, and these were correctly described in 21 cases (84 per cent). Ultrasonic investigation is a reliable, useful method to confirm, locate and evaluate traumatic muscular lesions and to assess the need for surgical repair.     

Bruxism, temporo-mandibular dysfunction and botulinum toxin]

Tooth grinding and tooth clenching are unvoluntary mainly nocturnal habits that result in an hypertrophy of masseter and temporalis muscles with an unbalance between opening and closing muscles of the jaw and lead to an alteration of mandibular condyles movements and to hyper pressure in the temporo-mandibular joints (TMJ) which can generate severe pain. Intra muscular injections of botulinum toxin permit to restablish the balance between closing and opening muscles, to relieve pain, to treat masseteric hypertrophy with improvement of face outline and to recover a normal cinetic of temporo-mandibular joints. Moreover, botulinum toxin injections permit to quit habits of tooth grinding and clenching and one single session of injections is curative for 2/3 of the patients. There are no side effects apart from slight diffusion to superficial muscles of the face resulting in a "fixed" smile for about 6 to 8 weeks. So injections of botulinum toxin in masseter and temporalis muscles are an efficient treatment of bruxism and TMJ dysfunction, cheap with no lasting side effect.     

Cybernetic model of psychophysiologic pathways: III. Clinical impairment of tension and kinesthesia

It is unclear whether peripheral, subcortical or intracortical loops are directly involved between receptors in muscles and tendons and the cerebral cortex in signaling movement magnitude and muscular tension information. Previous experiments have indicated that this information does reach consciousness. Data from voluntary compression of springs and strain-gauge were analyzed in patients with unilateral focal lesions of the cerebral hemispheres. It was found that the perception of signals of muscular tension is abolished by lesions of the contralateral cortex near the central sulcus. It was concluded that the possibility exists of separate cortical projection areas for kinesthetic signals from muscles and from joints.     

Defective expression of plectin/HD1 in epidermolysis bullosa simplex with muscular dystrophy.

Epidermolysis bullosa simplex with muscular dystrophy (MD-EBS) is a disease characterized by generalized blistering of the skin associated with muscular involvement. We report that the skin of three MD-EBS patients is not reactive with antibodies 6C6, 10F6, or 5B3 raised against the intermediate filament-associated protein plectin. Immunofluorescence and Western analysis of explanted MD-EBS keratinocytes confirmed a deficient expression of plectin, which, in involved skin, correlated with an impaired interaction of the keratin cytoskeleton with the hemidesmosomes. Consistent with lack of reactivity of MD-EBS skin to plectin antibodies, plectin was not detected in skeletal muscles of these patients. Impaired expression of plectin in muscle correlated with an altered labeling pattern of the muscle intermediate filament protein desmin. A deficient immunoreactivity was also observed with the monoclonal antibody HD121 raised against the hemidesmosomal protein HD1. Furthermore, immunofluorescence analysis showed that HD1 is expressed in Z-lines in normal skeletal muscle; whereas this expression is deficient in patient muscle. Colocalization of HD1 and plectin in normal skin and muscle, together with their impaired expression in MD-EBS tissues, strongly suggests that plectin and HD1 are closely related proteins. Our results therefore provide strong evidence that, in MD-EBS patients, the defective expression of plectin results in an aberrant anchorage of cytoskeletal structures in keratinocytes and muscular fibers leading to cell fragility.     

Mechanical ventilation of patients with late stage Duchenne muscular dystrophy: management in the home.

Death in the late stage of Duchenne muscular dystrophy is most frequently a consequence of respiratory failure. Since muscles of ventilation become weakened the bellows mechanism fails insidiously. Patients exhibit symptoms of ventilatory insufficiency, the first to be noticed are those associated with CO2 retention: dyspnea, nightmares, increased heart rate, and increased blood pressure. Ten patients with late stage Duchenne muscular dystrophy have been supplied with mechanical aid for ventilatory assistance. The age of onset of respiratory distress needing mechanical assistance varied from 10 to 20 years. Meaningful survival after allegedly reaching the end stage has been from 2 to 7.5 years with an average of 3.4 years. With a caring family, these patients can have a meaningful life, even though they require continuous mechanical ventilatory aid.     

Dystrophin gene repair in mdx muscle precursor cells in vitro and in vivo mediated by RNA-DNA chimeric oligonucleotides

Point mutations in the dystrophin gene cause dystrophin deficiency and muscular dystrophy in the mdx mouse and a subset of patients with Duchenne muscular dystrophy. As an approach to gene therapy for muscular dystrophies due to point mutations, we have studied the ability of RNA-DNA chimeric oligonucleotides (chimeraplasts) to induce repair of the dystrophin gene in mdx mice. We have previously demonstrated that targeting chimeraplasts can repair the exon 23 point mutation in differentiated myofibers in vivo after intramuscular injection. For long-term benefit to patients with muscular dystrophy, any gene therapy technology must target not only differentiated myofibers but also undifferentiated muscle precursor cells that are involved in ongoing muscle repair. The focus of the current studies was to test whether chimeraplasts could repair the dystrophin mutation in mdx muscle precursor cells. Initial studies were done by transfecting a targeting chimeraplast into mdx myoblasts in vitro. Gene repair was demonstrated at the DNA, RNA, and protein levels in these cells, whereas treatment of the cells with a control chimeraplast resulted in no gene correction. After differentiation of mdx cells that had been treated with a targeting chimeraplast, immunoblot analysis demonstrated full-length dystrophin expression. By quantitative analysis of independent cultures, the amount of dystrophin expressed ranged from 2 to 15% of that expressed in wild-type cells, providing a measure of the efficacy of gene conversion in vitro. To extend the assessment to muscle precursor cells in vivo, we injected targeting and control chimeraplasts into muscles of mdx mice. When muscle precursor cells were subsequently derived from muscles injected with a targeting chimeraplast, we found that gene repair had occurred in these cells as well. These results, taken together, further demonstrate that chimeraplast-mediated gene repair may be effective as an approach to gene therapy for muscular dystrophies due to point mutations.     

Quantified electromyography of lower-limb muscles during level walking

The electromyography (EMG) of eleven different lower limb muscles of ten healthy subjects was quantified during normal level walking. The surface EMGs obtained were normalized, in percentage, to the activity obtained during an isometric maximum voluntary test contraction of each subject. The mean peak activities of the gluteus maximus, gluteus medius, rectus femoris, vastus medialis, vastus lateralis, biceps femoris and medial hamstring muscles occurred at heel-strike and were between 5 and 15% of max isometric EMG. The magnitudes of tibialis anterior and triceps surae muscular activity were higher than those of the other muscles investigated. Mean peak activity in tibialis anterior was 27%, in gastrocnemius medialis 42%, in gastrocnemius lateralis 19% and in soleus 40%. The important role of the triceps surae during walking was reflected in comparatively high muscular activity at push-off.     

Die Muskulatur in Untersuchung und Behandlung aus Sicht der ÄMM

Examination and treatment of the muscular system are essential in manual medicine. ÄMM is teaching these subjects in basic courses and in special trigger point- and muscle-courses. In certain muscles Type I (postural) fibres are predominating; these fibres tend to develop muscle spasm or muscle tightness. Through the spinal segment the phasic antagonist (with Type II fibres) of a tightened muscle is inhibited and weakened this way. In standard tests we can check the decreased ability for extension of muscles as well as the weakness of muscles according to a certain standard. Among other tests dynamic stereotype tests are used. To treat a decreased ability for muscle extension we have therapeutic techniques like relaxation or stretch. To re-activate weak muscles within motor pattern we use neurophysiological physiotherapeutic techniques. Treating decreased ability for extension of muscles is prior to the treating of muscle weakness.     

Activity of some proteolytic enzymes in normal and dystrophic human muscle.

1. The following proteolytic enzymes were measured in muscles of control subjects and patients with muscular dystrophies and related neuromuscular diseases: an elastase-like enzyme, carboxypeptidase A, carboxypeptidase B and pyroglutamyl peptidase. 2. Elastase-like enzyme and carboxypeptidase B did not show significant alterations in various disease conditions that were examined. 3. Carboxypeptidase A was moderately elevated in dystrophic as well as other diseased muscles. 4. Pyroglutamyl peptidase was not markedly altered in any disease condition except that is was slightly lower in dystrophic muscles.     

Ultrasonic tissue characterisation of skeletal muscle

Ultrasound techniques have been used for the non-invasive, quantitative characterisation of muscle tissue in normal subjects and volunteer patients. Radio frequency (RF) echoes from a volume of tissue have been digitised and analysed using computer techniques. Attention has been given to the correct positioning and orientation of the transducer during examination due to the importance of the angle dependence of the interaction of ultrasound with muscle fasciculi. Several different muscles in the leg, arm and back of normal subjects have been examined, whereas patient studies have concentrated on the vastus intermedius. Ultrasonic data from patients with muscular dystrophy have been correlated with measurements of muscle tissue density obtained using X-ray computerised tomography (X-ray CT). The technique shows that ultrasound can be used to differentiate between normal and diseased muscle quantitatively. Results indicate that pathological change can be detected and monitored earlier with ultrasound than with X-ray CT. These quantitative methods are now in use as a guide to the staging and monitoring of pathological change in muscle.