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Biomedical subjects

L Edström

Publications and source records attributed to L Edström.

At least 55 records · Page 3Linked to original sources

Effects of age on physiological, immunohistochemical and biochemical properties of fast-twitch single motor units in the rat.

1. Physiological, enzyme-histochemical, biochemical and morphometrical properties of fast-twitch single motor units were compared between young (3-6 months) and old rats (20-24 months) using the glycogen depletion technique. Monoclonal antibodies (mAbs) were used to identify the myosin heavy chain (MHC) composition in the muscle fibres of the motor unit (motor unit fibres) in order to facilitate correlative physiological, histochemical, biochemical and morphometrical studies. 2. Earlier observations on effects of age on contractile properties of fast-twitch motor units were confirmed and extended. That is, the duration of the isometric twitch, and the twitch and tetanus forces, were increased. Further, motor unit fibres were rearranged, occupying a larger territory and displaying an increased innervation ratio in old age, indicating a denervation-reinnervation process. 3. Motor units with muscle fibres expressing the novel IIX myosin heavy chain (MHC) were observed in both young and old animals, and they constituted the predominant motor unity type identified in the old animals. In contrast to the type IIX MHC motor units in the young animals, the type IIX MHC units in old age often contained muscle fibres which expressed either the type IIA or type IIB MHC, although type IIX MHC fibres were in the majority (so called 'IIX' MHC motor units), but motor units containing all these three fibre types were never observed. There were also single fibres co-expressing IIX and IIB MHCs in old age. 4. In the young animals the IIX MHC motor units had a higher (P less than 0.001) resistance to fatigue (fatigue ratio 0.45 +/- 0.11) than the type IIB MHC units (0.03 +/- 0.05), a succinate dehydrogenase (SDH) activity (0.62 +/- .007) intermediate (P less than 0.001) between those of type IIA muscle fibres classified according to myofibrillar ATPase activity after acid pre-incubation, i.e. type IIA ATPase, (0.84 +/- 0.13) and type IIB MHC motor unit fibres (0.20 +/- 0.04), and cross-sectional fibre areas (1650 +/- 320 microns 2) which were similar to those of type IIA ATPase muscle fibres (1460 +/- 150 microns 2) but smaller (P less than 0.001) than type IIB MHC motor unit fibres (4650 +/- 1180 microns 2).(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphatases↗

Welander's distal myopathy: clinical, neurophysiological and muscle biopsy observations in young and middle aged adults with early symptoms.

Nine young or middle aged patients with early symptoms of Welander's distal myopathy were subjected to a detailed neurological examination including quantitative sensory testing, determination of motor and sensory nerve conduction velocity (NCV), sensory nerve action potentials, electromyography (EMG) and muscle biopsy from the tibialis anterior muscle (TA). Slight weakness of the extensors of the fingers and hands was found in all nine patients, and of the dorsiflexors of the feet in seven. All patients had a distal sensory disturbance most prominent for temperature which agrees with earlier observations. EMG changes in TA and extensor digitorum communis (EDC) muscles were of myopathic type. Slight abnormalities compatible with either myopathy or early neuropathy were found in one muscle biopsy. These findings indicate that a neurogenic lesion affecting at least the peripheral sensory system is present at an early stage of Welander's distal myopathy and that the neurogenic lesion might precede the myopathic changes.

Adult↗

MHC composition and enzyme-histochemical and physiological properties of a novel fast-twitch motor unit type.

Determinations of fatigue ratio, twitch and tetanus tension, and contraction and half-relaxation times of the isometric twitch were made in 21 single fast-twitch motor units from the rat tibialis anterior muscle. Single motor units were functionally isolated by microdissection of the ventral root, and the glycogen depletion technique was used to demonstrate the muscle fibers in the unit. Morphological and immuno- and enzyme-histochemical methods were applied to serial muscle cross sections to characterize the muscle fibers in the unit. Three of the units had muscle fibers of the IIa type according to staining both for myofibrillar adenosinetriphosphatase after acid preincubation and with the use of monoclonal antibodies specific for myosin heavy chains (MHCs), i.e., the IIa-MHC isoform. The other 18 units were of the IIb type according to enzyme-histochemistry, but immunohistochemistry showed that in six of these units the muscle fibers exhibited the novel type IIx-MHC isoform and in the other 12 units the IIb-MHC isoform. It was found that the IIx motor units have contraction and half-relaxation times similar to those of types IIa and IIb units but have morphological, physiological, and biochemical properties that distinguish them from the latter two types.

Animals↗

The effect of excessive weight loss on skeletal muscle in man. A study of obese patients following gastroplasty.

Lean body mass, muscle biochemistry, enzymehistochemistry and muscle strength were analyzed before and after 10% and 18% body weight loss following gastroplasty in 16 obese patients. Subjective fatigue was also determined, using an arbitrary scale, before and after the operation. Lean body mass and alkali-soluble proteins (non-collagenic proteins) per DNA decreased significantly in the postoperative period. The proportions of type I and type II muscle fibers remained normal postoperatively. The muscle fiber area decreased significantly at 10% body weight loss, with a tendency towards restoration at 18% weight loss, despite continuing loss of lean body mass. Preoperatively the muscle strength, determined as maximum voluntary concentric and eccentric action of the knee extensor and flexor muscles, was not significantly different from that in sedentary, age-matched subjects, but was less than expected from the lean body mass, content of alkali-soluble proteins and muscle fiber size. Muscle strength was not significantly changed postoperatively. According to the fatigue scale, the patients' wellbeing was improved at 18% body weight loss compared with the preoperative status.

Adult↗

A normal male with an inherited deletion of one exon within the DMD gene.

We describe two brothers with identical inherited deletions of one single exon within the middle of the DMD gene; one brother has Becker muscular dystrophy diagnosed at 11 years of age, whereas the older brother is normal at 18. These results have implications for genetic counselling and prenatal diagnosis in families with Becker muscular dystrophy.

Adolescent↗

Fibre-type composition, structure and cytoskeletal protein location of fibres in anterior tibial muscle. Comparison between young adults and physically active aged humans.

Muscle biopsies were obtained from the anterior tibial muscle (TA) of 15 healthy, sedentary young (23-37 years) and 13 healthy and physically active elderly (66-77 years) volunteers. The mean frequency of type I fibres was lower in the young subjects compared with the elderly, but the mean type I fibre cross-sectional area was equal in the two groups. The type IIA fibres were, however, smaller in the elderly than in young subjects. Capillary density, capillary per fibre ratio, capillaries in contact with type I fibres (CC) and CC in relation to type I and type II fibre area did not differ in the two groups. The number of capillaries in contact with type IIA fibres was higher in the younger group. Only occasional and minor pathological changes were observed in the young subjects. In the elderly, such changes were much more common, including central nuclei, ring fibres, fibre splitting, scattered highly atrophic fibres, moth-eaten fibres and vacuoles. Ring fibres were most easily identified with anti-desmin labelling and highly atrophic fibres exhibited a rough network of labelling. Increased content of actin and spectrin was also observed at the periphery of ring fibres. In the elderly group, a qualitative ultrastructural analysis was also obtained and obvious changes included some myofilament loss, collections of lipofuscin which were also observed in satellite cells, proliferation of the SR-T systems and increased wrinkling of nuclear membranes and sarcolemma.

Adult↗

Myopathy with respiratory failure and typical myofibrillar lesions.

16 patients representing 7 different pedigrees exhibited an unusual, adult onset limb-girdle myopathy with typical clinical hallmarks. In a majority of cases there was evidence of an autosomal dominant inheritance. A prominent early finding in all cases was respiratory muscle weakness, and in many of these an acute respiratory incapacity was the reason for the first neurological examination. Neck flexor and sometimes foot extensor weakness were other early symptoms. The clinical picture seems to be at variance with that of the more well known hereditary myopathies. Electrophysiological analysis confirmed a myopathy and serum muscle enzyme concentrations were normal or slightly elevated. Muscle biopsy findings revealed myofibrillar changes which, at the light microscopy level, included plaques that stained strongly with rhodamine-conjugated phalloidin, a specific marker for F-actin. At the ultrastructural level, these plaques were observed to be composed of moderately dense, thin filaments and were related to splitting of Z-discs or formed extensions from Z-discs. We believe that the muscle biopsy changes revealed by cytochemical and ultrastructural observations indicate defective myofibrillogenesis, and the possibility of defective actin polymerization is discussed. A conclusive answer requires further immunocytochemical and immunoelectrophoretic studies and possibly the application of molecular genetics.

Adult↗

Influence of ATP turnover and metabolite changes on IMP formation and glycolysis in rat skeletal muscle.

Deamination of AMP to inosine monophosphate (IMP) and NH3 is thought to be regulated by the observed increases in ADP, AMP, and H+. We have examined this hypothesis by comparing the rate of IMP accumulation in contracting and noncontracting rat skeletal muscle. The rate of IMP formation was high during ischemic contraction, and consistent with previous studies, formation of IMP was associated with high levels of muscle lactate, depletion of phosphocreatine (PCr), and increased levels of ADP and AMP. When the contraction period was followed by 5-min anoxic recovery, the metabolic changes were maintained, but no further IMP or lactate was formed. During long-term (2-4 h) anoxia, the rate of IMP formation was less than 4% of that during contraction, despite similar changes in PCr, lactate, ADP, and AMP. It is concluded that the observed changes in the intracellular chemical environment are not sufficient to explain the high rate of IMP formation during contraction but that a combination of metabolic stress and a high ATP turnover rate is required. It is suggested that a high ATP turnover rate during conditions of metabolic stress results in transient increases in ADP and AMP at the site of ATP hydrolysis and that these activate AMP deaminase and glycolysis. An alternative hypothesis is that these processes are regulated by the increase in cytosolic Ca2+ in a contracting muscle.

Adenosine Diphosphate↗

Neurogenic involvement in distal myopathy (Welander). Histochemical and morphological observations on muscle and nerve biopsies.

Patients with distal myopathy (Welander) were subjected to muscle biopsy from the anterior tibial muscle (n = 4) and to nerve biopsy from the sural nerve at the ankle (n = 5) in order to elucidate a possible neurogenic component of the disease. The type I muscle fibres had a larger mean cross-sectional area as compared to normal controls and an increased variation in fibre size with both hypertrophic and atrophic fibres in one and the same biopsy. A normal muscle fibre type composition was found in the patients. Structural muscle fibre abnormalities such as atrophic fibres, mainly angulated, split fibres, rimmed vacuoles and centrally located nuclei were found in all biopsies. A disorganization and loss of myofibrils as well as autolytic vacuoles were the most prominent findings at the ultrastructural level. Two patients had a moderate loss of myelinated sural nerve fibres. The mean nerve fibre density was decreased as compared to normal controls while the mean nerve fibre area and circular diameter were increased due to selective loss of small diameter (A-delta) nerve fibres. The muscle and nerve fibre abnormalities are discussed with reference to neuropathic and myopathic changes. Some muscle fibre abnormalities are typical for a neurogenic disorder while some others are mostly seen in myopathies but may also appear in neurogenic conditions. A neurogenic etiology in Welander distal myopathy is further supported by the finding of loss of small diameter nerve fibres in the sural nerve.

Adult↗

Intracellular elemental composition of single muscle fibres in muscular dystrophy and dystrophia myotonica.

Seven patients with myotonic muscle dystrophy (MD), 6 with muscle dystrophy without myotonia (limb-girdle and facio-scapulo-humeral dystrophy) and 6 healthy volunteers were subjected to biopsy from the anterior tibial muscle (TA). Light microscopic examination of cryostat sections revealed pathological changes of different kind and degree--the occurrence of ring fibres and multiple central nuclei was the most consistent in advanced MD. X-ray microanalysis (XRMA) of single muscle fibres demonstrated the intracellular content of such elements as Na, Cl, K, Mg, S and P. The most conspicuous finding was the increase in Na and Cl and decrease in K demonstrated in MD. The highest levels of Na and Cl were found in ring fibres. Decrease in K was as high in structurally normal fibres of MD biopsies as in ring fibres and was also found in the muscle dystrophies without myotonia, but to a lesser degree than in MD. Thus, the decrease in K was not correlated to increase in Na and Cl. These changes in muscle fibre elemental content are discussed in relation to plasma membrane changes of erythrocytes in MD and especially the indications of disturbed anion channels.

Adult↗

Motoneuron firing and isomyosin type of muscle fibres in prior polio.

In patients with prior polio there was an excessive use of remaining motor units and an absence of type II muscle fibres in the tibialis anterior (TA). In the present study, eight subjects with prior polio with more than 90% type I fibres in the TA were examined. The aim was to elucidate whether the lack of type II muscle fibres was due to a selective loss of motoneurons with high threshold and high axonal conduction velocity or due to a muscle fibre transition from type II to type I. There was no decrease of the proportion of motoneurons with high threshold and high axonal conduction velocity. Monoclonal antibodies against fast and slow myosin heavy chains (MHC) were used as histochemical markers and many muscle fibres of type I according to ATPase stainability showed a binding of both anti-fast and anti-slow MHC. It is suggested that the type I muscle fibre dominance in prior polio subjects with excessive use of TA during walking is due to a muscle fibre transition from type II to type I and not to a loss of one class of motor units.

Adult↗

Effect of short time denervation on intracellular elemental content and fibre atrophy pattern of slow and fast twitch rat muscle.

Fast twitch extensor digitorum longus (EDL) and slow twitch soleus (S) muscles were studied after 5 and 16 days of denervation. Elemental contents of single muscle fibres were obtained with energy dispersive X-ray microanalyses (XRMA) applied on cryosections visualised in the scanning or scanning-transmission mode of electron microscopy. Cross sections in series with those produced for analytical electron microscopy were stained for enzyme histochemical fibre typing. A similar increase of Na and Cl was observed in EDL and S fibres after 16 days of denervation and a decrease of K was observed as well in EDL. This time after denervation is known to correspond to the maximal acetylcholine receptor synthesis extrajunctionally. There were no changes of elemental content after 5 days and thus the early membrane changes as i.a. fall in resting membrane potential and increased permeability for Na as well as increased endocytosis did not correspond to changes detectable by XRMA. Time course of atrophy differed between histochemical fibre types in EDL. In S all the muscle fibres atrophied earlier than in EDL and without any difference between fibre types. Then changes in elemental composition of muscle fibres after denervation do not seem to be related to degree and time course of muscle fibre atrophy.

Animals↗

Energy dispersive X-ray microanalysis, neutron activation analysis and atomic absorption spectrometry--comparison using biological specimens.

X-ray microanalysis, neutron activation analysis and atomic absorption spectrometry were performed on normal and injured skeletal muscle. X-ray microanalysis of tenotomized rat soleus muscle showed significantly elevated levels of sodium and chlorine and lower potassium compared with normal muscle. Similar ion shifts could be demonstrated by neutron activation analysis and atomic absorption spectrometry. The concentrations of sodium and chlorine obtained by these techniques were somewhat higher and that of potassium lower than the values obtained by X-ray microanalysis. This can probably be attributed to the fact that in atomic absorption spectrometry and in neutron activation analysis the entire muscle biopsy contents are measured while in X-ray microanalysis only the content of muscle cells unaffected by extracellular, non-muscular components are determined. It can be concluded that X-ray microanalysis is a reliable technique to study the elemental content of biological tissue, especially tissue undergoing pathological changes affecting the extracellular spaces. Other types of analysis should be used when elements not detectable by X-ray microanalysis are of interest.

Activation Analysis↗

Use of motor units in relation to muscle fiber type and size in man.

The use of the musculus tibialis anterior during walking and the type and size of its muscle fibers were determined in 15 young normal subjects (29 +/- 4 years) and in 13 old healthy subjects (70 +/- 3 years). In the average step cycle 16 +/- 6% of the maximal surface EMG was recorded during the swing phase and 44 +/- 15% during 100 msec at the heel strike. Single motor unit recordings showed that low-threshold units fired at 10-15 Hz during the swing and at 20-25 Hz during the heel strike peak. Usually, high-threshold units did not participate in the ordinary step cycle. A significantly higher mean use was found in the old subjects as compared with the young ones presumably due to lower muscle power in relation to body weight. In the young subjects 76 +/- 7% of the muscle fibers were type 1 and 22 +/- 7% were type 2A. In the old subjects 84 +/- 9% were type 1 and 15 +/- 8% were type 2A. In the young subjects the mean cross-sectional area of type 1 fibers was 3950 +/- 950 microns2 and of type 2 fibers was 8070 +/- 1850 microns2. In the old subjects the corresponding numerals were 4050 +/- 890 microns2 and 5700 +/- 1970 microns2, respectively. The significance of physiological variations in use for muscle fiber type composition and size is discussed.

Adult↗

Effects of excessive use of remaining muscle fibers in prior polio and LV lesion.

Twenty-three subjects with weakness of musculus tibialis anterior (TA) due to prior poliomyelitis (n = 19) or prior LV lesion (n = 4) were examined regarding the use of remaining TA motor units during walking and the consequences of long-term overuse for the TA muscle fibers. Subjects with an excessive overuse exhibited almost only type 1 muscle fibers and with marked hypertrophy. Subjects who did not use remaining TA fibers because of too-severe paralysis had a normal fiber type differentiation and fiber atrophy. The use of remaining TA motor units was correlated to the type 1 muscle fiber percentage (r = 0.69) and to the type 1 fiber size (r = 0.78). Identical changes were observed in subjects with prior poliomyelitis and in subjects with prior LV lesion and were, thus, not specific for poliomyelitis. The changes in fiber type composition may be explained by a transition of type 2 to type 1 muscle fibers in accordance with previously reported experimental transneuronal stimulation through implanted electrodes in animals.

Adolescent↗

Effects of chronic nicotine exposure on contractile enzyme-histochemical and biochemical properties of fast- and slow-twitch skeletal muscles in the rat.

Nicotine-exposed and control rats were compared with respect to contractile, enzyme-histochemical and biochemical properties of fast- and slow-twitch skeletal muscles in order to elucidate the mechanisms underlying previously observed effects of tobacco smoking on skeletal muscle. The nicotine was administered in drinking water, since this approach has been shown to result in a plasma nicotine pattern similar to that seen in tobacco smokers. In a pilot study, fibre-type proportions and mitochondrial enzyme activities tended to change in the slow-twitch soleus muscle after 9 weeks of nicotine exposure in a way similar to that previously reported in tobacco smokers. In the present study, the duration of nicotine exposure was more prolonged (18 weeks) and the number of studied animals was increased. In this series neither contractile, enzyme-histochemical nor biochemical properties were affected by the nicotine exposure. It is thus concluded that prolonged nicotine exposure has no significant effect on the skeletal muscle characteristics studied, and that other aetiological agent(s) for the observed differences in such characteristics between smokers and non-smokers should be searched for.

Animals↗