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Desmin, the muscle-specific intermediate filament protein, is one of the earliest markers expressed in all muscle tissues during development. It forms a three-dimensional scaffold around the myofibril Z-disc and connects the entire contractile apparatus to the subsarcolemmal cytoskeleton, the nuclei and other cytoplasmic organelles. Desmin is essential for tensile strength and muscle integrity. In humans, disorganization of the desmin network is associated with cardiac and/or skeletal myopathies characterized by accumulation of desmin-containing aggregates in the cells. Currently, 49 mutations have been identified in desmin gene. The majority of these mutations alter desmin filament assembly process through different molecular mechanisms and also its interaction with its protein partners. Here, we will give an overview of desmin network organization as well as the impact of desmin mutations on this process. Furthermore, we will discuss the different molecular mechanisms implicated in perturbation of the desmin filament assembly process.

Muscle fiber action participates in a true contractile machinery associated with noncontractile components providing mechanical stability. The myofibril, the muscle fiber subentity, has an extremely consistent architecture, composed of longitudinal cylindrical units called sarcomeres, the skeletal muscle length functional unit, a highly important place in the transduction of chemical signal into mechanical contractile energy, for the most part mediated by calcium. The sarcoplasmic reticulum is the other major component of muscle fiber and is dedicated to calcium storage, liberation and distribution to the fiber, under the influence of action potential propagation. This phenomenon is called excitation-contraction coupling. This paper explores muscle anatomy from its main embryologic stages of development to its histochemical specificity, including its molecular constitution, and details the main morphofunctional relations supporting muscle contraction.

Early and severe cardiomyopathy may be related to myofibrillar myopathy.We report a one-year-old child with early and severe restrictive cardiomyopathy. The diagnosis of myofibrillar myopathy was obtained on skeletal muscle and endomyocardial biopsies. The patient died despite inotropic support and mechanical ventilation.Myofibrillar myopathy must be considered when exploring the etiology of a restrictive cardiomyopathy in children. The diagnosis relies on examination of endomyocardial or skeletal muscle biopsy samples.

During embryonic and foetal development, the masseter is formed from two successive generations of muscle fibers in a manner which is very similar to that which has been previously described for other skeletal muscles. This phenotype is characterised by the persistence of ontogenic myosin isoforms (embryonic and foetal myosin heavy chains, embryonic light chain) and by the presence of two distinct populations of fibers: small diameter fibers which coexpress the embryonic, foetal and fast isoforms of the myosin heavy chains but never express the slow isoform; large diameter fibers which express the slow myosin heavy chain either exclusively or in variable associations with the other isoforms. These characteristics of the human masseter muscle probably correspond not only to its embryological origin and its special innervation, but also to the functional constraints to which it is submitted after birth.

In the diaphragm muscle, postnatal maturation is associated with major histological and biochemical modifications, as well as a progressive development of the sarcoplasmic reticulum (SR), which in turn are responsible for the progressive postnatal improvement in diaphragmatic contractility. However, the mechanisms by which postnatal maturation induces this improvement in diaphragmatic contractility remain poorly understood and controversial. The aim of this review is to analyze the data from the literature regarding the process involved in the postnatal improvement in diaphragmatic contractility.References obtained from Pubmed((R)) databank using keywords (diaphragm muscle, postnatal maturation, contractility, muscular fatigue, cross-bridge).From a cytological point of view, the postnatal development of the diaphragm muscle is processed in two successive generations of fiber types, corresponding to the progressive adaptation of the diaphragm muscle to its physiological function. Indeed, the proportion in type I (slow, aerobic) and type IIB fibers (fast, anaerobic) progressively increases with postnatal maturation, while the proportion in type IIA fibers (fast, intermediate) progressively decreases. The histochemical classification of the type of fiber corresponds to the expression of the different isoforms of myosin heavy chains (MHC). Two types of MHC: MHC embryologic (MCH-emb) and MHC neonatal (MCH-neo), and one type of myosin light chains (MLC) are expressed in the foetal skeletal muscles, then are progressively eliminated during postnatal maturation. For many authors, this progressive transition from immature MHC (MCH-emb and neo) to adult MHC (by chronological order of appearance: MHC-2A, MHC-lente, MHC-2X, MHC-2B) could be responsible for the progressive improvement in postnatal diaphragmatic contractility. This transition could be modulated by external factors, mainly including neural and hormonal stimuli. For others, this transition in MHC expression do not play a major role, and other factors, including the postnatal maturation of the ryanodine receptor (RyR) or developmental changes in cross-bridges (CB) properties should play a central role. The most recent hypotheses proposed included the possibility of a postnatal transition in the expression of structural proteins, which are playing a major role in the maintenance of the stability of the sarcomer, and therefore in force generation.

The aim of the experiment was to determine the influence of concurrent gestation and lactation in rabbit does on the post-natal growth and muscular characteristics of the progeny. Myosin heavy chain (MHC) isoform proportion, myofibrillar protein content and size of the myofibres were determined on day 29 or day 70 in the semitendinosus muscle of young rabbits born from either simultaneously pregnant and lactating does (PL group) or from only pregnant does (P group). There were no significant differences in the weight of the young rabbits of the two groups throughout the post-natal period, despite a non-significant reduction of birth weight by 9% in the PL group. On day 29, the proportion of perinatal MHC was higher (5.8% vs 2.3%) and that of the type-II isoforms was lower (91.5% vs 95.0%) in the PL group than in the P group (P < 0.01). The simultaneous gestation and lactation affected the maturation of secondary fibres. On day 70, the proportion of the MHC isoforms was similar in the two groups. These results suggest that concurrent gestation and lactation delayed the myofibrillar maturation rate.

A biological study of masticatory muscle behaviour (Divry and Westphal, 1991) suggested the analysis of physiologic correlates (biologic parameters related to a behavioural event) such as histochemical reactions of muscular fibres studied by M-ATPase and SDH activities. For such investigations, routine methods are needed. In the present study, a modification of the original method of Tunell and Hart (1977) was used, in which three features of the original alkaline preincubation method (composition, incubation time and pH) were modified. These allowed a single step differentiation of the various fibre types found in rat masticatory muscles, for which the classical technics gave only a weak contrast, not suitable for image analysis. Acid preincubation was also tested but failed to give new information. By combining this modified technic with SDH staining (Nachlas, 1957) a classification of fibres into 12 theoretical types was proposed.

In a family 6 members in 3 generations were affected by centronuclear myopathy (CNM) of autosomal dominant inheritance. The apparent onset was in the early forties and the disease progressed slowly. Limb weakness was predominant. Strabismus was present in 5 cases and calves hypertrophy in 3. Serum creatinine kinase was always within the normal range. In one case myotonic bursts were found at electromyography. In 2 cases brain stem auditory evoked potential studies demonstrated abnormal prolongation of interpeak latencies I-III and favoured subclinical nervous system involvement. Muscular biopsies showed typical features of centronuclear myopathy with 50 to 80% central nuclei. In two cases immunocytochemical labelling of dystrophin showed staining in the sarcoplasm in favour of an arrest in the morphogenesis of developing myofiber. Others families with autosomal dominant CNM in the literature and also some sporadic adult cases had similar clinical features.

Various substances, called neurotransmitters, act as a chemical relay between the nervous and the tissue of the lower urinary tract. Some play also a role inside the muscle cell modulating the activity of the myofibrils. To allow a better pharmacochemical approach, these substances are described, their activity analyzed, with the purpose of helping specialists concerned by investigation or treatment of the lower urinary tract, to be able to act on their activity or change their pathologic abnormalities.

Twenty-four endomyocardial biopsies performed during surgical correction of valvulopathies were compared with ventricular function. Patients were divided into three groups: group I without anomalies of ventricular function, group II with a slight decrease of the ventricular ejection fraction, group III with a low ventricular ejection fraction. Morphometric analysis was carried out using electron microscopic photographs and an image analyser. The results were correlated with those of functional studies. In patients of the second group, the small number of mitochondria with respect to the increased myofibrillary area seemed to indicate mitochondrial dysfunction. In patients of the third group, alterations of myocontractility expressed a myofibrillary deficiency unable to be corrected by the multiplication and the increased exchange areas of mitochondria.

Myofibrils from rat hearts were prepared in conditions maintaining their redox state, and their sulfhydryl groups were measured using a solution of urea and sodium dodecyl sulfate (SDS) as denaturant. The sulfhydryl content was 92 n mol/mg of protein, indicating that cysteins are in reduced form. In the presence of superoxide radicals generated in vitro with purine and xanthine oxidase, the myofibrillar sulfhydryl groups were oxidized.

In order to obtain a better understanding of the anorectal continence in the newborn child, the development of the anorectal sphincter was studied in 25 embryos (3 to 60 mm CR), sectioned in the sagittal, transversal and frontal planes. A macroscopic study was also performed in 20 human embryos, completed by a light microscopic study and by a morphometric analysis of the smooth and striated components of the sphincter. The anorectal sphincter is composed of three parts: the external sphincter, which appears in the early embryos as a condensation of mesenchymal tissue around the anorectum. It receives smooth longitudinal fibers later; the m. puborectalis appears before 10 weeks and forms a sling around the anorectum; the internal sphincter, which is only well differentiated at 10 weeks and grows after the rupture of the anal membrane. This study emphasizes the importance of the anorectum in the development of its own sphincter.

A fragment of septum was removed for biopsy in 11 patients with obstructive cardiomyopathy who were undergoing surgery. Electron microscopi revealed an increase in the numbers of mitochondria, deposits of glycogen, and deforming fibrosis. As far as the components of muscle fibres are concerned, both lysis and synthesis of neosarcomeres are to be found, together with abnormalities of the Z band and disorientation of the myofibrils. The number and severity of these abnormalities were found to vary from patient to patient and also in different sections. Although these features are virtually constant in cases of obstructive cardiomyopathy, they are not specific for this condition; they are also found in cases of non-obstructive hypertrophic cardiomyopathy.

Myofilaments have been prepared from crab legs according to a technique derived from that of F.J. Julian (1971). Tension variations have been recorded while the isolated fiber was submitted to the action of different saline solutions. As expected, it could be confirmed that the tension mainly depends on the content in Ca++ and Mg++ ions and in ATP. Our results have also shown that monovalent ions (Na+ and K+) when added separately, produce an important tension increase wheras their simultaneous addition or withdrawal modifies the tension only slightly.

Recent research has shown that the cytoplasm of several varieties of non muscular cells contains contractile proteins similar to those of striated muscle (actin and myosin, with the control complex of troponin and tropomyosin). Using indirect immunofluorescent staining with specific antisera, the authors demonstrate that the cytoplasm of the cells of oral squamous cell carcinoma contains actin, myosin and actinin (tropomyosin seems to be lacking). They have found these contractile proteins inconstantly in various precarcinomatous states, but never in normal epithelium, except in a few basal cells. In electronic microscopy, these contractile proteins correspond to a network of microfilaments of 40-80 A, more rarely 100-120 A, Clearly different from tonofilaments, located mainly in the peripheral part of the cytoplasm, just under the plasmalemmal membrane. It is tempting to speculate that the occurence of a contractile filamentous apparatus in the cells of oral carcinomas--already described in skin and mammal gland carcinomas--allows to these cells amoeboid movements and active migration, which might to some extent explain their tendency to invade surrounding tissues and to produce metastasis.

Central axis myopathy is one of the commonest congenital myopathies. It is transmitted above all by a dominant autosomal mode, but sporadic cases are numerous. Clinically, it is characterised by neonatal hypotonicity, delayed slow motor development in the young child, but the diagnosis may be mode only in adult life. There is preferential involvement of the muscles of the pelvis girdle, muscle wasting otherwise remaining moderate in general. Various skeletal malformation are fairly often present in association. the electromyogram is of myogenic type. The disorder does not show any marked progression. By light microscopy, the central axis is more clearly seen by stains such as PAS, trichromes, and haematoxylin phospho-tungstic. In most cases it is the sole finding and is seen in a variable number of fibres, not only from one patient to another, but from one muscle to another. The rest of the fibre may be normal or show various lesions with no specific characteristics. Histoenzymology may show rarefaction or disappearance of the II fibres, relative hypotrophy of I or II fibres, or the absence of any oxidative phosphorylase activity in the central axis. The latter shows changes with regard to ATPase activity ("structured core" and "non-structured core"). Electron microscopy shows changes in varying degree in the axis, possibly to the extent of myofibrillary destruction, contrasting with the absence of or only slight changes in the rest of the fibre. Two cases, one in a child and the other in a 24-year-old woman, are reported, illustrating the above findings. Various interpretations have been suggested for this condition. Certain authors accept the existence of progressive transformation of the II fibres, whilst others describe pathology of the Z striae or a disturbance in the distribution of the mitochondria. Similarities with other muscular lesions, in particular rod myopathy, have been envisaged.

The toxicity of nitrite and especially of nitrosamines lay down an important problem. The assessment of dangers for the man depends for a great part of the knowledge of the form of nitrite in the diet. The estimate of the part of "free nitrite" and "bound nitrite" in the cured meat products is a first access of this problem.

Previous investigations described two kinds of enigmatic ultrastructures in Hydra mesogloea, "tubular bodies" and "particles". Evidence is presented that "tubular bodies" are cytoplasmic spiral processes, 1 500 A thick, often containing polysaccharidic particles (900 A in diameter). Large extracellular "particles" (450-800 A) are also identified as polysaccharides. These particles are enclosed in a meshwork of closely arranged fibrils. The relationship of the "tubular bodies" to polysaccharidic extracellular particles is discussed.

A new lethal case of nemaline myopathy is reported. Muscle biopsy at 20 days of age permitted the diagnosis but this boy died at the 35th day of life. In a review of the literature (15 similar cases) the authors analyse the diagnostic, histopathogenic, genetic and evolutive aspects of this heterogeneous disorder, apparently less "benign" than previously thought.

We report a case of a boy of 13 who was born with muscular hypotony which has tended to improve over the course of the years. We was examined for the first time when he was 4 years old and a diagnosis was made of "congenital myopathy". Examination showed curved feet, gothie palate, severe laxity of the ligaments, and spider fingers which evoked Marfan's syndrome. The present myopathy is concentrated in the shoulder girdle and the E.M.G. showed "myogenic" tracings. Biopsy of the deltoid showed the presence of large numbers of rods in all muscle fibers stained with Engel's modified trichromic stain, localized mainly under the sarcolemma. Histochemical staining showed no evidence of differences in the fibers, all of which had the same enzymatic activity. A diagnosis was made of nemaline myopathy. As we were able to follow clinical progress in this case for nine consecutive years we could confirm that not only was the disease non-progressive but that it was regressing in this patient.

The authors present and illustrate most of the ultrastructural abnormalities encountered in skeletal muscle in cases of neuromuscular disease. The diagnostic significance of the changes are discussed but emphasis is laid on the nonspecific character of most of them. For diagnostic purposes, examination by light microscopy remains the preferred approach, but electron microscopy enables the nature and origins of the lesions to be better defined and is a very valuable technique in exploring the pathogenesis of muscular diseases.

The effect of the reperfusion on the pathological appearance of experimental myocardial infarction has been studied in the rat (87 animals). Following permanent ischemia (33 animals sacrified after 1, 6, 24 and 48 hours), there appeared a reproducible extended transversal infarction marked by an uniform sequence of histologic, histoenzymatic and ultrastructural changes. Following temporary ischemia (54 animals), the pathological patterns were marked by myofibrillar degeneration (contraction band necrosis), cellular edema, calcium deposits and interstitial hemorrhages. These changes appeared after reperfusion of short duration (10 minutes). Sarcolemmal and capillary permeability alterations could be the main factor involved in the reperfusion injury. Similar tissue damage have been found in clinical conditions in subendocardial hemorrhagic necrosis after cardiopulmonary by-pass, and in reperfused infarction.

Cardiac and skeletal muscles exhibit regularly spaced light and dark transverse striations (the I and A bands respectively). Consequently, when they are illuminated by a laser beam, they behave like diffraction gratings. The diffraction line spacing varies inversely with the sarcomere length. Real-time kinetics of sarcomere can be measured with a high accuracy. The analysis of the diffraction pattern indicates a high degree of synchronization of sarcomere movements (contraction and relaxation). This technique represents a powerful method to analyse the mechanical behaviour of heart muscle at subcellular level.

Ultra microscopic study of three glomic tumours established the presence in these of myoepithelial cells with a cytoplasma rich in fibrils and deprived of secretory granules. These typical cells are very different of these of chimioreceptors of chromophile system.

Experiments have been carried out to explore the proteolytic cleavage of rabbit skeletal myofibrils by a calcium dependent neutral proteinase (CaANP). Polyacrylamide gel elctrophoresis on great slabs showed the ability of CaANP to degrade myofibrils more readily than supposed. Besides the hydrolysis of troponin T and the apparition of degradation product of 30,000 molecular weight, the activity of this enzyme is obvious too on some components of the M-line and on heavy subunits of tropomyosin as well as on three unidentified proteic fractions. The variety of the degradation products which appear suggest that the specificity of CaANP is not as selective as presumed. The participation of this proteinase in the postmorten evolution of muscle and its intervention in the turnover of myofibrillar proteins is discussed.

An electron microscope study of the arrector pili muscle, using biopsies obtained from clinically and histologically healthy skin in 3 cases of scleroderma, showed the primary origin of the muscle disorders. They showed a certain number of changes, both of the differentiated cytoplasm and of the common cytoplasm.

Two cases, one being probably familial, of ocular myopathy are reported. In both the onset was in childhood by ptosis of the eyelids and the course lasted more than 20 years. The patients (32 and 49 years) presented involvement of the ocular muscles as well as of the facial, pharyngolaryngeal, neck and limb muscles. There was, in both cases, marked body weight loss which could not be explained by the muscular atrophy alone, and a thyroid nodule which was not accompanied by evident change in thyroid function. Muscle biopsy studies were carried out : electron microscopy showed in both cases aggregates of mitochondria exhibiting various changes ; in one case histochemistry demonstrated that these changes were confined to type 1 muscle fibres. These cases of descending ocular myopathy can be included therefore in the group of the smaller than myopathies with abnormal mitochondria greater than.

The mechanical performance of the myocardium depends upon factors intrinsic to the myofibrils ("contractility") and upon the physicochemical conditions surrounding the cells ("inotropic state"). A precise description of cardiac muscle performance requires a knowledge of 4 variables: length, force, velocity and time. In vivo the problem is further complicated by the presence in the ventricle of spatio-temporal nonuniformities (activation sequence, fiber orientation) and by the fact that major determinants of the inotropic state, such as sympathetic tone, are hard to verify. The indices expected to reflect the tension-velocity-length relation of the myofibrils, either during isovolumic contraction (peak(+)dP/dt) or during ejection (end-systolic relations between pressure or stress and volume, relations between ejection fraction and stress) can generally detect acute changes in inotropic state. Up to now, however, none of these indices has been shown to be very sensitive in detecting basal alterations in contractility. Considering the practical and theoretical limitations on study of an intact ventricle, it would appear indispensable, if we want greater precision in detecting functional alterations of the myocardium, to supplement study of ventricular mechanics by biochemical and morphological analysis of the myocardium.

We present some observations differing from the idea that neurons precisely control the differentiation of muscle fibre histochemical properties and show that, in a few cases, innervation does not influence the development of myofibrillar ATPase properties. Moreover, we report that a regional variation of the acid stability of myofibrillar ATPase may occur in the polar zone of intrafusal fibres in chick PLD muscle spindles, a zone devoid of innervation. This observation is related to a similar variation in the polar zone of rat intrafusal fibres (Kucera et al., 1978). New examples are presented supporting the conclusion that the differentiation of the properties of ATPase activity, and thus of fibre types, takes place, at least in some cases, independently of the type of innervation received.