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Biomedical subjects

Y Cherel

Publications and source records attributed to Y Cherel.

At least 19 recordsLinked to original sources

Morphological alterations in oxidative muscles and mitochondrial structure associated with equine atypical myopathy.

REASONS FOR PERFORMING STUDY: There is a lack of well documented studies about muscular lesions in equine atypical myopathy (EAM). OBJECTIVES: To characterise morphopathological changes of striated muscles and myocardium, to progress understanding of this disease. METHODS: Thirty-two horses age 0.5-7 years kept on pasture were referred for a sudden ataxia/myoglobinuria syndrome. Clinical examination (stiffness, muscle pain, muscle fasciculations, abnormal gait, recumbency, myoglobinuria, tachycardia, sweating) and plasma CPK, LDH and AST levels were consistent with extensive myonecrosis and, together with anamnestic data, with so-called 'equine atypical myopathy' (EAM), a disease of unknown aetiology reported since 1939. Macroscopic and microscopic (histology, histoenzymology, ultrastructure) lesions were evaluated. RESULTS: Necropsic examination revealed large areas of muscle necrosis, the extent and severity of which varied between cases and muscles, but which were clearly more constant and severe in respiratory and postural muscles and in the myocardium. Histology highlighted a multifocal and monophasic process compatible with Zenker degeneration/necrosis that mostly and segmentally affected type 1 fibres. Histochemical evaluation revealed a weak and disorganised pattern of NADH tetrazolium reductase staining, the absence of calcium salts precipitates and a dramatic accumulation of lipid droplets. Ultrastructural examination often revealed fibres of which the sole modifications were altered mitochondria and sarcoplasmic lipidosis. CONCLUSIONS: Taken together, the data suggest that a primary alteration of mitochondria should be considered, although secondary mitochondrial abnormalities have yet to be ruled out. POTENTIAL RELEVANCE: The morphological features gathered here reveal that EAM shares most of the characteristics of toxic myopathies.

Animals↗

Phosphate stimulates matrix Gla protein expression in chondrocytes through the extracellular signal regulated kinase signaling pathway.

Whereas increasing evidence suggests that inorganic phosphate (Pi) may act as a signaling molecule in mineralization-competent cells, its mechanisms of action remain largely unknown. The aims of the present work were to determine whether Pi regulates expression of matrix Gla protein (MGP), a mineralization inhibitor, in growth plate chondrocytes and to identify the involved signaling pathways. Chondrogenic ATDC5 cells and primary growth plate chondrocytes were used. Messenger RNA and protein analyses were performed by quantitative PCR and Western blotting, respectively. The activation and role of MAPKs were, respectively, determined by Western blotting and the use of specific inhibitors. Immunohistological detection of ERK1/2 was performed in rib organ cultures from newborn mice. The results indicate that Pi markedly stimulates expression of MGP in ATDC5 cells and primary growth plate chondrocytes. Investigation of the involved intracellular signaling pathways reveals that Pi activates ERK1/2 in a cell-specific manner, because the stimulation was observed in ATDC5 and primary chondrocytes, MC3T3-E1 osteoblasts, and ST2 stromal cells, but not in L929 fibroblasts or C2C12 myogenic cells. Accordingly, immunohistological detection of ERK1/2 phosphorylation in rib growth plates revealed a marked signal in chondrocytes. Finally, a specific ERK1/2 inhibitor, UO126, blocks Pi-stimulated MGP expression in ATDC5 cells, indicating that ERK1/2 mediates, mainly, the effects of Pi. These data demonstrate, for the first time, that Pi regulates MGP expression in growth plate chondrocytes, thereby suggesting a key role for Pi and ERK1/2 in the regulation of bone formation.

Animals↗

Restoration of vision in RPE65-deficient Briard dogs using an AAV serotype 4 vector that specifically targets the retinal pigmented epithelium.

Previous studies have tested gene replacement therapy in RPE65-deficient dogs using recombinant adeno-associated virus 2/2 (rAAV2/2), -2/1 or -2/5 mediated delivery of the RPE65 gene. They all documented restoration of dark- and light-adapted electroretinography responses and improved psychophysical outcomes. Use of a specific RPE65 promoter and a rAAV vector that targets transgene expression specifically to the RPE may, however, provide a safer setting for the long-term therapeutic expression of RPE65. Subretinal injection of rAAV2 pseudotyped with serotype 4 (rAAV2/4) specifically targets the RPE. The purpose of our study was to evaluate a rAAV2/4 vector carrying a human RPE65cDNA driven by a human RPE65 promoter, for the ability to restore vision in RPE65-/- purebred Briard dogs and to assess the safety of gene transfer with respect to retinal morphology and function. rAAV2/4 and rAAV2/2 vectors containing similar human RPE65 promoter and cDNA cassettes were generated and administered subretinally in eight affected dogs, ages 8-30 months (n = 6 with rAAV2/4, n = 2 with rAAV2/2). Although fluorescein angiography and optical coherence tomography examinations displayed retinal abnormalities in treated retinas, electrophysiological analysis demonstrated that restoration of rod and cone photoreceptor function started as soon as 15 days post-injection, reaching maximal function at 3 months post-injection, and remaining stable thereafter in all animals treated at 8-11 months of age. As assessed by the ability of these animals to avoid obstacles in both dim and normal light, functional vision was restored in the treated eye, whereas the untreated contralateral eye served as an internal control. The dog treated at a later age (30 months) did not recover retinal function or vision, suggesting that there might be a therapeutic window for the successful treatment of RPE65-/- dogs by gene replacement therapy.

Animals↗

Stable isotope evidence of diverse species-specific and individual wintering strategies in seabirds.

Although there is increasing evidence that climatic variations during the non-breeding season shape population dynamics of seabirds, most aspects of their winter distribution and ecology remain essentially unknown. We used stable isotope signatures in feathers to infer and compare the moulting (wintering) habitat of subantarctic petrels breeding at two distant localities (South Georgia and Kerguelen). Petrels showed species-specific wintering habitat preferences, with a similar pattern of latitudinal segregation for all but one taxon. At both localities, delta13C values indicated that blue petrels (Halobaena caerulea) moult in Antarctic waters, South Georgian diving petrels (Pelecanoides georgicus) in the vicinity of the archipelagos and/or in the Polar Frontal Zone and Antarctic prions (Pachyptila desolata) in warmer waters. In contrast, common diving petrels (Pelecanoides urinatrix) showed divergent strategies, with low and high intrapopulation variation at South Georgia and Kerguelen, respectively. Birds from Kerguelen dispersed over a much wider range of habitats, from coastal to oceanic waters and from Antarctica to the subtropics, whereas those from South Georgia wintered mainly in waters around the archipelago. This study is the first to show such striking between-population heterogeneity in individual wintering strategies, which could have important implications for likely demographic responses to environmental perturbation.

Animal Migration↗

Using stable isotopes to study resource acquisition and allocation in procellariiform seabirds.

Some procellariiform seabirds use a dual strategy for provisioning their chicks by alternating short (ST) and long (LT) foraging trips. Parent birds gain mass during LT but they lose mass while increasing the chick feeding frequency during ST. Self-feeding during LT is crucial for the success of ST because firstly most of the energy used during ST is likely to be derived from the energy stored during LT and secondly self-feeding during ST is presumed to be negligible. Self-feeding by adult procellariiforms is thus a key issue to understand allocation processes but it is still poorly known. We tested these predictions by using the stable isotope (delta(15)N and delta(13)C) technique on birds' plasma and prey with the short-tailed shearwater Puffinus tenuirostris breeding at Tasmania as a model. Parent shearwaters returning to the colony after a LT have an Antarctic/subantarctic delta(13)C signature in their plasma (-23.8 per thousand), thus indicating that they fed in cold waters, far away from their breeding colony, for their own maintenance. Parent birds returning to the colony after a ST also have a distant Antarctic/subantarctic delta(13)C signature in their plasma (-24.3 per thousand), thus verifying that self-feeding is negligible during ST and that birds fast at that time, using energy stores built up in cold waters. Plasma delta(15)N values of adults (8.8 per thousand) indicates they mainly prey upon zooplankton-eating organisms, probably mesopelagic myctophid fishes. A simple isotopic mixing model estimates that they consume by mass 87% myctophids and 13% subantarctic krill when self-feeding. Finally and as expected, the carbon isotopic signature of chick plasma (-22.2 per thousand) was intermediate between those of high- and low-latitude marine organisms and is thus in agreement with chicks being fed with a large diversity of prey species caught by adult birds from Antarctic to Tasmanian waters. One main consequence of this system is that reproduction of a Tasmanian species is controlled by resources available at great distances from the breeding colony that drive allocation decisions of parent birds.

Animal Migration↗

Aluminium hydroxide-induced granulomas in pigs.

The effect of intramuscular injection of 40 mg/2 ml aluminium hydroxide in the neck of pigs was examined in a number of ways. The investigation followed repeated slaughterhouse reports, according to which 64.8% of pigs from one particular farm were found at slaughter to have one or more nodules in the muscles of the neck (group slaughtered). The pigs had been injected with a vaccine containing 40 mg/2 ml dose of aluminium hydroxide as adjuvant. Research consisted of two phases: first, an epidemiological study was carried out, aimed at determining the risk factors for the granulomas. The results indicated that the vaccine was to be held responsible for the formation of granulomas. A clinical trial was then performed to further substantiate the initial hypothesis, by comparing pigs, which were aseptically inoculated twice with either the original vaccine or the adjuvant alone (groups vaccine and adjuvant) to pigs inoculated twice with apyrogenic bi-distilled water (group water) and to pigs inoculated once with the adjuvant and once with apyrogenic bi-distilled water (group adjuvant/water). Both studies agreed in their conclusions, which indicate that the high amount of aluminium hydroxide was the cause of the granulomas.

Adjuvants, Immunologic↗

Seasonal variations of a battery of biomarkers and physiological indices for the mussel Mytilus galloprovincialis transplanted into the northwest Mediterranean Sea.

Seasonal variations of six mussel (Mytilus galloprovincialis) biomarkers at two sites in the Mediterranean Sea were compared with physiological indices (condition, growth and gonad maturation), environmental parameters (temperature, salinity and turbidity), and chemical contamination levels. The basal levels of acetylcholinesterase (AChE), DNA adducts, benzo[a]pyrene hydroxylase (BPH), heat-shock proteins (HSP70), metallothioneins (MT) and P-glycoprotein (P-gp)-mediated multixenobiotic resistance (MXR) were estimated as early warning signals in caged mussels sampled at Carteau (native site) and La Fourcade (transplantation site) over a 2-year period. The Carteau and La Fourcade mussels have specific chemical contamination profiles but a similar range of values. For example, both are highly contaminated by heavy metals (201 and 258.4 mg kg(-1) dw, respectively) and considered as moderately impacted for polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs). However, contamination levels at Carteau are twice as high for PAHs (101.5 mg g(-1) dw) and PCBs (90.2 mg g(-1) dw) than La Fourcade. The seasonal contamination trend at Carteau showed six-fold higher levels of pyrolytic pollutants in winter. Although few tissue lesions were detected in individuals studied at either site, greater parasitic infestation was observed at Carteau. The results of findings from the two Mediterranean pilot studies support the adaptability of transplanted mussels to be used as biomarkers and to establish physiological endpoints for chemical contaminant exposure.

Animals↗

Recombinant adeno-associated virus type 2 mediates highly efficient gene transfer in regenerating rat skeletal muscle.

The recent identification of genes responsible for several muscle diseases, particularly inherited myopathies, has made gene transfer to pathologic muscle tissue an attractive research field. As early pathologic changes in myopathic muscle involve repeated necrosis-regeneration cycles, leading to the coexistence of myofibers at different stages of maturity, a delivery system for efficient, durable gene therapy of inherited muscle diseases should allow gene transfer into myofibers at any stage of maturity. Experiments with rat skeletal muscles showed that recombinant adeno-associated virus (rAAV) type 2 can be highly efficient and even improve gene transfer in regenerating as compared with mature muscle, provided that vector injection is performed during the myotube growth period of the regenerative process. At this early period of muscle regeneration, young regenerating myotubes strongly express heparan sulfate proteoglycan AAV type 2 receptor. Improvement was associated with a greater number of transduced myofibers in muscle samples and an increase in viral genomic copies in transduced muscle. No significant deleterious effects on muscle phenotype or any evident alterations in the regenerative process were observed in transduced muscles. Unlike other available viral vectors, whose transduction efficiencies are highly maturation-dependent, rAAV type 2-based vectors provide efficient in vivo gene transfer in myofibers at various stages of maturity, making AAV a promising delivery system for pathological muscle tissue.

Animals↗

Alterations of the MDV oncogenic regions in an MDV transformed lymphoblastoid cell line.

AIMS: Lymphoblastoid cell lines derived from Marek's disease virus (MDV) induced tumours have served as models of MDV latency and transformation. They are stable and can be cultured with no detectable MDV genomic alterations upon repeated passaging. An MDV transformed lymphoblastoid T cell line (T9 cell line) has been reported to contain a disrupted MDV BamHI-H fragment and a Rous associated virus insertional activation of the c-myb protooncogene. In an attempt to define the respective participation of c-myb and MDV in the transformed phenotype of T9 cells, an analysis of MDV oncogenic sequences (BamHI-H, BamHI-A, and EcoQ fragments) was performed in these cells. METHODS: Using two different passages of the T9 cell line (late and early passages), the organisation of the MDV oncogenic regions and their expression in these cells were analysed. In vivo assessment of the oncogenicity of the virus contained within these cells was assessed by injecting them into 1 day old chickens. RESULTS: In T9 cells maintained in culture for up to six months (late T9), the MDV ICP4 gene was disrupted, whereas the meq gene was actively transcribed. The alterations of the MDV genome in these cells correlated with the inability of the virus to induce the classic signs of Marek's disease in 1 day old chickens. However, early T9 cells submitted to a limited number of passages induced classic MDV pathogenicity, as efficiently as the MDV control cell line (T5), and did not show gross structural changes in the oncogenic MDV sequences. CONCLUSIONS: Although the expression pattern of the MDV oncogenes in early T9 cells was identical to the one reported for other MDV transformed cells, longterm culture of an MDV transformed cell line containing a RAV insertional activation of the c-myb protooncogene led to the disruption of the MDV BamHI-H and BamHI-A oncogenic regions. In the late T9 cells MEQ was the only detected MDV oncoprotein. These results suggest that in the late T9 cells the truncated MYB protein compensates for the loss of MDV oncoproteins and reinforce the possibility that MEQ and MYB cooperate in the maintenance of the transformed state and the tumorigenic potential of these cells.

Animals↗

X-linked vacuolated myopathy : TNF-alpha and IFN-gamma expression in muscle fibers with MHC class I on sarcolemma.

The presence and the distribution of tumor necrosis factor-alpha, interferon-gamma, and p65 subunit of nuclear factor-kappaB, molecules known to induce synergistically and to mediate major histocompatibility complex (MHC) class I expression, were determined in muscle sections from control and X-linked vacuolated myopathy patients. MHC class I colocalized with tumor necrosis factor-alpha and interferon-gamma, as well as with p65, in most of the membrane attack complex- and/or calcium-positive muscle fibers in X-linked vacuolated myopathy. These results suggest that the expression of MHC class I in X-linked vacuolated myopathy could be induced by tumor necrosis factor-alpha and interferon-gamma and partly mediated by nuclear factor-kappaB.

Gene Expression Regulation↗

Evidence of p53 mutation in an early stage of liver cancer in European flounder, Platichthys flesus (L.).

A number of flounders dwelling in highly contaminated coastal areas of Northern Europe develop liver tumours. In order to increase our understanding of the molecular pathogenesis of these sporadic tumours, we examined p53 mutations in eleven hyperplasia and six adenoma. p53 introns 4 to 8 were first sequenced to allow individual amplification of exons 5 to 8. DNA extracted from formalin-fixed livers was amplified and PCR products were directly sequenced. Two major results were obtained. (i) Flounders from different geographical areas displayed a high rate of sequence variation. Base substitutions were identified in both tumour and normal tissues and thus may be considered as polymorphic variations in individuals. (ii) One mutation was detected in two hyperplastic foci from the same flounder. This mutation was a T:A to A:T transversion at codon 147, resulting in the replacement of valine for glutamic acid. This residue took place in the L2 loop of the DNA binding surface. Its substitution by an hydrophilic and charged residue could thus impair p53 (protein) biological activity.

Adenoma, Liver Cell↗

Hyaluronidase enhances recombinant adeno-associated virus (rAAV)-mediated gene transfer in the rat skeletal muscle.

Skeletal muscle is a privileged target for long-term rAAV-mediated gene transfer in mouse, rat, dog and non-human primates. Intramuscular injections of rAAV encoding human factor IX in hemophilia B patients have been initiated, based on promising results gathered in affected dogs. We found that intramuscular rAAV administration in rats resulted in restricted transduction essentially along the myofibers axis with poor lateral diffusion. This suggested that the transduction rate might be limited by the ability of the virus to reach sites distant from the injection point. We tested whether hyaluronidase, an enzyme which dissociates the extracellular matrix, could enhance vector diffusion when injected in the rat muscle before administration of rAAV encoding either nuclear-localized beta-galactosidase (rAAVCMVnlsLacZ) or the human alpha-1-antitrypsin (rAAVCMVhAAT) under the control of the cytomegalovirus immediate--early promoter (CMV). The results showed that pretreatment of the rat anterior tibialis muscle with hyaluronidase resulted in: (1) a larger diffusion of the virus indicated by an increase in the area containing LacZ-transduced fibers, and (2) a two- to three-fold increase of transduction efficiency measured by the number of LacZ-positive fibers or by the hAAT serum concentration. We also provide evidence that hyaluronidase was well tolerated and was not associated with short- or long-term toxicity evaluated by morphological studies. Finally, in our experimental conditions, hyaluronidase did not promote rAAV dissemination to other organs as assessed by PCR to detect vector sequences. We conclude that pretreatment of skeletal muscle by hyaluronidase, a clinically available reagent, was harmless and resulted in a consistent and significant increase in rAAV diffusion and transduction levels.

Animals↗

Histopathological and immunohistochemical studies of lesions associated with Ebola virus in a naturally infected chimpanzee.

Lesions caused by the Côte d'Ivoire subtype of Ebola virus in a naturally infected young chimpanzee were characterized by histopathological and immunohistochemical methods. The predominant lesions consisted of multifocal necrosis in the liver and diffuse fibrinoid necrosis in the red pulp of the spleen. In these sites, macrophages contained large eosinophilic intracytoplasmic inclusion bodies. Immunohistochemical staining indicated that macrophages were a major site of viral replication. The absence of bronchiolar and pulmonary lesions and the paucity of antigen-containing macrophages in the lung suggested that aerosol transmission by this animal was unlikely. There were necrotic foci and antigen-containing macrophages in intestinal lymph nodes, in association with lesions caused by intestinal parasites, suggesting the possibility of virus entry through the digestive tract.

Animals↗

Factors influencing recombinant adeno-associated virus production.

Recombinant adeno-associated virus (rAAV) is produced by transfecting cells with two constructs: the rAAV vector plasmid and the rep-cap plasmid. After subsequent adenoviral infection, needed for rAAV replication and assembly, the virus is purified from total cell lysates through CsCl gradients. Because this is a long and complex procedure, the precise titration of rAAV stocks, as well as the measure of the level of contamination with adenovirus and rep-positive AAV, are essential to evaluate the transduction efficiency of these vectors in vitro and in vivo. Our vector core is in charge of producing rAAV for outside investigators as part of a national network promoted by the Association Française contre les Myopathies/Généthon. We report here the characterization of 18 large-scale rAAV stocks produced during the past year. Three major improvements were introduced and combined in the rAAV production procedure: (i) the titration and characterization of rAAV stocks using a stable rep-cap HeLa cell line in a modified Replication Center Assay (RCA); (ii) the use of different rep-cap constructs to provide AAV regulatory and structural proteins; (iii) the use of an adenoviral plasmid to provide helper functions needed for rAAV replication and assembly. Our results indicate that: (i) rAAV yields ranged between 10(11) to 5 x 10(12) total particles; (ii) the physical particle to infectious particle (measured by RCA) ratios were consistently below 50 when using a rep-cap plasmid harboring an ITR-deleted AAV genome; the physical particle to transducing particle ratios ranged between 400 and 600; (iii) the use of an adenoviral plasmid instead of an infectious virion did not affect the particles or the infectious particles yields nor the above ratio. Most of large-scale rAAV stocks (7/9) produced using this plasmid were free of detectable infectious adenovirus as determined by RCA; (iv) all the rAAV stocks were contaminated with rep-positive AAV as detected by RCA. In summary, this study describes a general method to titrate rAAV, independently of the transgene and its expression, and to measure the level of contamination with adenovirus and rep-positive AAV. Furthermore, we report a new production procedure using adenoviral plasmids instead of virions and resulting in rAAV stocks with undetectable adenovirus contamination.

Animals↗

Early stages of rabbit haemorrhagic disease virus infection monitored by polymerase chain reaction.

In order to define more accurately the initial events that take place during rabbit haemorrhagic disease virus (RHDV) infection, different organs of experimentally infected rabbits were analysed for the presence of the virus and correlated with histopathological observations. A total of 24 rabbits were intranasally inoculated with a viral suspension, and tissue samples were taken from the liver, spleen, kidney, lung, thymus, lymph node and tonsil at different intervals post-inoculation (2, 4, 6, 12, 18, 24, 30, 36, 48, 50, 51, 70 and 72 h). Histopathological observations revealed the presence of the first significant lesions at 30 h post-inoculation (p.i.) in the liver. Using an ELISA and a haemagglutination test (HAT), the virus was detected in the liver at 36 h p.i. The reverse transcriptase-polymerase chain reaction (RT-PCR) showed that the RHDV RNA was present as early as 18 h p.i. in the liver and spleen, whereas thymus, kidney, tonsil and lymph node were found to be positive after more than 36 h p.i. The lungs presented a variable positivity between 0 and 36 h p.i., but remained positive after this time.

Animals↗

Gastrointestinal tract protein synthesis and mRNA levels for proteolytic systems in adult fasted rats.

We studied protein turnover in the gastrointestinal tract of adult fasted rats, since the mechanisms responsible for protein wasting in these tissues are poorly understood. Protein mass of stomach, small intestine, and colon decreased by 14-29 and 21-49% after 1 and 5 days of fasting, respectively. The fractional rate of in vivo protein synthesis (ks) was approximately 34% lower in the stomach after 1 and 5 days of fasting due to decreased capacity for protein synthesis (Cs). In small intestine and colon, ks was not different after 1 day, but was approximately 26% lower on day 5, mainly because of a reduction in Cs. Thus protein wasting in the stomach is primarily mediated by decreased protein synthesis but not in small intestine and colon during short-term fasting. To determine which proteolytic systems may be activated in the gut, we measured mRNA levels for critical components of the lysosomal (cathepsins B and D), Ca(2+)-activated (m-calpain), and ubiquitin-dependent (ubiquitin, 14-kDa ubiquitin-conjugating enzyme E2, and C8, and C9 proteasome subunits) proteolytic pathways. mRNA levels for most of these components increased during fasting, suggesting that a coordinated activation of multiple proteolytic systems contributed to intestinal protein wasting.

Animals↗

The osteoclast generation: an in vitro and in vivo study with a genetically labelled avian monocytic cell line.

Osteoclasts are multinucleate giant cells responsible for bone resorption. Osteoclast precursors are hematopoietic mononucleate cells, which give rise to osteoclasts after fusion. Nevertheless, the precise stage of differentiation where osteoclast precursors diverge from other hematopoietic lineages is still debated. We describe here both in vitro and in vivo approaches to the study of the osteoclast differentiation pathway. We used cells of the BM2 avian monocytic cell line, which are able to differentiate into macrophages both in vitro and in vivo. In order to follow the progeny of BM2 monocytes, we have derived a BM2 cell clone expressing the nlslacZ gene (BM2nlslacZ) which has still retained the main features of the parental cell line. In vitro, when BM2nlslacZ cells were triggered toward macrophages, they participated in the formation of multinucleate osteoclast-like cells as seen by their blue nuclei. Furthermore, when BM2nlslacZ cells were injected into the blood stream of chicken embryos, they could give rise to blue nucleate macrophages in the bone marrow, as well as to osteoclasts with blue nuclei in bone. Finally, we have shown that fusion of tagged mononucleate precursor cells not only occurs with other mononucleate precursor cells but also with mature multinucleate osteoclasts. This work shows that cells already engaged in the late stages of the monocytic differentiation pathway are able to differentiate into osteoclasts and that osteoclast divergence takes place after the monocyte stage.

Animals↗

Type-specific changes in fibre size and satellite cell activation following muscle denervation in two strains of turkey (Meleagris gallopavo).

Morphological features and the chronology of muscle changes after denervation were studied over a 21 d period in 2 heavy (HW) and light-weight (LW) strains of 6-wk-old male turkeys. The atrophy of tibialis cranialis, gastrocnemius lateralis and plantaris muscles was apparent at d 3 after denervation. By d 21 the weight of these muscles had reached 45-60% of that of nondenervated contralateral muscle. Cellular lesions, such as irregularities in mitochondrial distribution or coagulative necrosis with fragmentation and lysis associated with moderate infiltration of inflammatory cells, were similar in both strains. Ten days after denervation, immunolabelling of a proliferating cell nuclear antigen (PCNA) expressed during the G1 and S phase of the cell cycle revealed satellite cell activation in denervated muscles. The number of satellite cells activated at d 21 was markedly greater in the HW than LW strain. Morphometric analysis revealed that fast twitch (type II) fibres were atrophied after denervation, whereas slow-twitch (type I) and slow tonic (type III) fibres were hypertrophied from d 10. Hypertrophy occurred more rapidly in the LW than HW strain.

Animals↗