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Intrafusal muscle fibres in adult muscle spindles differ in their myosin composition. After selective motor denervation intrafusal muscle fibres develop mature ultrastructural characteristics. In order to evaluate the role of fusimotor innervation on the maturation of the myosin composition of intrafusal muscle fibres we have examined with immunohistochemical techniques i) the postnatal development of muscle spindles in new-born rats and in 7-21 day old rats; ii) muscle spindles in the EDL of 21-day-old rats de-efferented at birth. For the characterization of myosins in intrafusal fibres we used three myosin antisera: antipectoral myosin, antiheart myosin and antiheart myosin adsorbed with muscle powder from the soleus muscle of guinea pig. We show in this study that during development intrafusal fibres change immunoreactivity and that in the absence of motor innervation bag fibres do not fully develop the myosin characteristics of control spindles. We conclude that the maturation of bag and bag fibres apparently requires next to the inductive influence of sensory axon terminals the presence and activity of fusimotor axons. [ABSTRACT FROM AUTHOR]

The understanding haematological malignancies at the protein level is important for the prediction of therapy response, the possibility for disease diagnostics, the development of targeted treatment, and it must be based on the knowledge regarding the molecular pathogenesis of the tumour. 'Proteomics' describes the analysis of the entire proteome of a cell or a tissue and incorporates multiple technologies, including - Western blotting, two-dimensional polyacrylamide gel electrophoresis, mass spectrometry, and ProteinChip-based technology. Although there is a limited number of studies to date in haematological malignancies, those performed highlight the potential impact of these technologies in the discovery of novel markers associated with the drug resistance and the identification of biomarkers which may facilitate the development of a rapid diagnostic test that would be easily applicable in the clinical setting. Thereby this article describes used proteomics techniques and highlights studies regarding proteomic research in haematological malignancies, namely the primarily publications concerning research of multiple myeloma, leukaemias and lymphomas.

Our experiments addressed the problem of the regulation of the number of mechanoreceptors by sensory axons and/or their peripheral target tissues. According to a previous study (Zelená et al. 1997) white leghorn chickens have more muscle spindles in the plantaris muscle (45.4+/-7.8; mean+/-SD) than the Japanese quail (35.3+/-4.8) and significantly more Herbst corpuscles in the crural region (380.0+/-85.0) than the quail (124.9+/-32.8). Embryonic chick-quail chimeras were therefore used as a model with distinct recombinations of the nerve supply and peripheral tissue for studying the developmental control of these mechanoreceptors. The chick host leg bud was replaced with a quail leg bud of equal age and vice versa on embryonic day 3, prior to the onset of innervation of the periphery. Shortly before hatching the chimeras were sacrificed and muscle spindles and Herbst corpuscles counted. Recombinations of chicken nerves with quail limb buds have shown that the richer nerve supply by chick Ia axons induced a significant increase in the number of muscle spindles in the plantaris muscles (55.5+/-13.4) of the grafted quail limb. In some instances, a similar increase in spindle numbers was also found in control legs grafted onto hosts of the same species. In the reverse type of chimera where chick embryo legs were grafted onto quail hosts, spindles developed in lower numbers (27.3+/-3.2). In that case the lower number of Ia axons in quail nerves induced a lower number of spindles in the chicken muscle. The numbers of Herbst corpuscles were, however, low in both types of chimera. Quail legs grafted onto host chick embryos contained 126.8+/-26.4 corpuscles, presumably due to a restrictive influence of the smaller crural area in the quail. Chick legs grafted onto quail hosts had only 99.6+/-34.1 crural corpuscles; the target area in chick embryo legs failed to attract more quail axons and/or to induce axonal sprouting. The developmental regulation of the number of the two types of mechanoreceptors examined in our study thus differ. While sensory axons appear to play the dominant role in the development of muscle spindles, their role seems to be restricted by hitherto unknown peripheral factors during the development of Herbst corpuscles.

Herbst corpuscles were studied in the crural region of perinatal and adult chicken and quail in order to find out their number and dimensions and to learn more about their structure, especially in relation to size. Crural corpuscles are arrayed in an encapsulated string between tibia and fibula. They are closely packed together; a small number of corpuscles is found apart from the string, often attached to the periost. The strings of corpuscles are approximately 40 mm long in adult chicken and 20 mm long in the quail. The crural region of the chicken contains 382.8 +/- 90.9 (mean +/- SD) corpuscles, the numbers ranging from 301 to 582; in the quail, the mean number is 119.2 +/- 27.9, with a range from 83 to 167 corpuscles. In the chicken, one axon supplies an average of 1.60 corpuscles; in the quail, the relation of axons to corpuscles is approximately 0.92. In both species, final numbers of crural corpuscles are already attained before hatching and no difference is found in the mean number and range of corpuscles between perinatal and adult birds. In both chicken and quail, individual strings contain corpuscles of various sizes, from large to very small. The chicken corpuscles are generally twice as large in diameter and often longer than those of the quail. The corpuscles are composed of an axon terminal that projects two rows of axonal spines into the clefts of the inner core and ends with an ultraterminal bulb; the terminal is surrounded with a bilaterally symmetrical inner core, amorphous inner space containing collagen fibrils of various thickness, and a capsule. Large chicken corpuscles contain inner cores composed of up to 100 lamellae, while quail inner cores have half that number at the most. The capsules are usually composed of 8 to 10 lamellar layers in both species, but they are thicker in the chicken than in the quail. The possible functional significance of individual structural components of Herbst corpuscles is discussed.

Tactile lamellar corpuscles were studied after freeze injury of rat toe pads under normal conditions and following permanent denervation in 1- to 65-day-old animals. In the innervated skin, digital corpuscles redifferentiated in all age groups examined during development and maturation. Characteristic of the reinnervated skin was a great diversity in the shape and size of newly formed corpuscles. Small corpuscles with only 1-3 lamellae around their terminals and well-developed corpuscles of about normal size with up to 15 lamellae were sometimes found within the same sample of skin. The regenerated corpuscles were reduced in number; they reappeared in only 50% of dermal papillae in the toe pads after freeze injury in 7-week-old rats, compared with approximately 100% of dermal papillae that contained lamellar corpuscles in normal toe-pad skin. In denervated toes, occasional corpuscular lamellar structures appeared first after freeze injury applied to 34-day-old rats. In the toe pads denervated and injured by freezing in 42- and 49-day-old rats, lamellar structures redifferentiated in about 10% of the papillae, and in 23.5% after freeze injury applied to 2-month-old rats. Unsatisfactory preservation of basal laminae at the former sites of the corpuscles and in the acellular peripheral nerve stumps, and/or insufficient migration of Schwann cells, may be responsible for the absence or abortive regeneration of lamellar structures in denervated skin of food pads after freeze injury in young rats.

The development of Meissner-like lamellar corpuscles was studied in rat toe pads under normal conditions and after crushing the sciatic nerve in 1- to 15-day-old animals. During normal development, rat lamellar corpuscles begin to differentiate first by postnatal day 8. By this time, sensory axons have grown up to the apex of dermal papillae and form axon terminals beneath epidermis. The terminals are ensheathed by lamellar cells derived from Schwann cells. First thin lamellae are formed around the terminals 8-12 days after birth, and the number of lamellar layers increases until the corpuscles become structurally mature by 20 days after birth. A mature corpuscle consists of two or more terminals, each surrounded by approximately 10 lamellae, all components being enclosed by an incomplete capsule. No lamellar corpuscles develop in toe pads after crushing the sciatic nerve in newborn rats, and only occasional corpuscles regenerate after nerve crush at 5 days of age. The corpuscles fail to develop because dermal papillae remain permanently denervated after crushing the nerve early postnatally. After nerve crush in 10-day-old rats, lamellar corpuscles regenerate by 1 month after the operation, but they remain underdeveloped: their number and size are smaller than normal even 1 year after injury, and their terminals are encircled only by 1-3 lamellar layers. After nerve crush in 15-day-old rats, the corpuscles recover upon reinnervation and their size and lamellation become almost normal.

The ultrastructure of Pacinian corpuscles of the cat located in the crural region and innervated by the interosseous nerve was studied 1 to 14 months after denervation. Both the Pacinian inner core and capsule remained well preserved one month after denervation. However, the denervated inner cores underwent progressive atrophy and wasting, which resulted in a gradual reduction of the amount of inner-core cells and lamellae, widening of interlamellar clefts, formation of empty spaces in the axial region and a considerable increase in the number of collagen fibrils. In spite of the wasting, the inner core still survived 14 months after denervation, but at least half of its volume became occupied by collagen fibrils which surrounded the remaining inner-core cells and lamellae. Collagen fibrils assembled in the denervated core were markedly thinner than those found in the capsule, as is also the case in normal Pacinian corpuscles. In the capsule, discrete focal degeneration, occasional pyknosis of the innermost capsular cells and macrophage infiltration were observed from the first month after nerve section onward, but the number of capsular layers remained within the normal range (30-40) up to 14 months after denervation.

It has been established previously that muscle stretch receptors of the rat fail to develop after neonatal denervation, but differentiate in full number per muscle after de-efferentation, when sensory innervation remains preserved. Recent immunocytochemical and morphometric studies have revealed, however, that some properties of stretch receptors are altered after motor denervation. In de-efferented muscle spindles, the maturation of myosin of the nuclear bag fibres becomes arrested. In de-efferented tendon organs, the mean length becomes increased and mean width decreased in in extensor digitorum longus muscles which become prolonged after de-efferentation, whereas the opposite changes occur in de-efferentation soleus muscles which become shortened. In spite of these alterations, however, neonatal de-efferentation does not impede the differentiation of ultrastructural characteristics and functional properties of stretch receptors. Thus motor innervation and muscle function are dispensable, whereas sensory innervation is absolutely essential for the development of stretch receptors.

The slow anterior latissimus dorsi (ALD) muscles of newly hatched chickens were transposed and cross0innervated by the mixed, predominantly fast superior brachialis nerve, and investigated 2 to 15 months after the operation. Two months after the operation, myosin ATPase activity of the cross-innervated ALD muscles was still as low as in the control ALD, although the ultrastructure and the histochemical ATPase activity already showed a mixed fibre-type pattern with a predominance of fast -type fibres around the site of nerve implantation. The change of myosin properties of thw whole cross-innervated ALD did not occur until the third month after the operation. At that time, the myosin ATPase activity increased about 2.5 times and light chains of myosin of the fast type appeared in the electrophoretic pattern. The myosin ATPase activity attained 62% of the activity found in the control fast posterior latissimus dorsi muscles at three months; subsequently it remained at about this level reaching 68% 18 months after the operation. The results indicate that approximately two thirds of the cross-innervated ALD muscle fibres became changed towards the fast type under neural influence, whereas about one third remained slow, being re-innervated by the slow-type motor fibres of the implanted nerve.

The nuclear ultrastructure of muscle fibres in congenital myofibrillar hypoplasia of piglets was studied in order to provide more information on the pathological changes present. In the initial stages of the disease, muscle fibres with a small reduction of myofibrils often had an increased number of nuclear pores. In the more advanced stages of the disease, the following nuclear abnormalities were observed in muscle fibres showing an extensive disintegration of myofibrils: 1) large dilations of the perinuclear cisternae, 2) small nuclear protrusions projecting into these dilations and 3) appositions of stray membranes of the disrupted endoplasmic reticulum to the nuclear envelope. The increase in the number of nuclear pores may be significant in the development of pathological changes in congenital myofibrillar hypoplasia which is thought to be a hereditary disease. The observed abnormalities of the nuclear envelope appear to be characteristic for muscle fibres undergoing degeneration.