Apport de la tomographie par émission de positons au 18F-fluorodéoxyglucose (TEP-FDG) dans la prise en charge du cancer du canal anal

ObjectiveTo evaluate the contribution of FDG-PET in the management of anal carcinoma, with special emphasis on its impact on therapeutic strategy.Materials and methodsFrom March 2005 to August 2008, 48 PET were performed on 43 patients with anal epidermoid carcinoma, in initial staging (IS: 20 exams), therapeutic response assessment (TRA: 11), and recurrence assessment (RA: 17). We compared initial therapeutic strategies defined on conventional assessment results, to final ones chosen after PET.ResultsPET revealed lesions that were undetected by conventional investigation in 23% of cases (IS: 25%; TRA: 18%; RA: 23%) and cleared suspicious lesions in 21% of cases (IS: 10%; TRA: 18%; RA: 35%). It influenced the therapeutic strategy, and sometimes even modified it radically, in 44% of cases (IS: 35%; TRA: 54%; RA: 47%). This therapeutic impact was stronger in settings with diagnostic ambiguity, in which PET allowed to specify the diagnosis and to orientate consequently the therapeutic choice.ConclusionPET is interesting in the management of anal carcinoma, especially in uncertain diagnostic settings, in which the metabolic information brought allows to influence the therapeutic choice in almost half of the cases.     

Phagocytosis is coupled to the formation of phagosome-associated podosomes and a transient disruption of podosomes in human macrophages

Phagocytosis consists in ingestion and digestion of large particles, a process strictly dependent on actin re-organization. Using synchronized phagocytosis of IgG-coated latex beads (IgG-LB), zymosan or serum opsonized-zymosan, we report the formation of actin structures on both phagocytic cups and closed phagosomes in human macrophages. Their lifespan, size, protein composition and organization are similar to podosomes. Thus, we called these actin structures phagosome-associated podosomes (PAPs). Concomitantly to the formation of PAPs, a transient disruption of podosomes occurred at the ventral face of macrophages. Similarly to podosomes, which are targeted by vesicles containing proteases, the presence of PAPs correlated with the maturation of phagosomes into phagolysosomes. The ingestion of LB without IgG did not trigger PAPs formation, did not lead to podosome disruption and maturation to phagolysosomes, suggesting that these events are linked together. Although similar to podosomes, we found that PAPs differed by being resistant to the Arp2/3 inhibitor CK666. Thus, we describe a podosome subtype which forms on phagosomes where it probably serves several tasks of this multifunctional structure.     

Hereditary retinoblastoma: can balanced insertion entirely explain the differences of expressivity among families?

Summary Although the retinoblastoma gene has been isolated and sequenced, the difference in penetrance and expressivity among families has not yet been fully explained. Balanced chromosomal insertion involving the 13q14 regions has been shown to account for some families with several unaffected carriers. Since there could be cases with karyotypically undetectable insertions, we tested whether this mechanism was general enough to explain the whole difference in expressivity among families. Using 166 pedigrees, reported in nine series available in the literature (including our own), we conclude that balanced insertion cannot entirely explain the familial data, even if we allow for a reduced viability of unbalanced gametes. Other mechanisms are proposed and discussed in this paper.     

Effects of electrical stimulation upon post-hatching development of fibre types in normally innervated fast and slow latissimus dorsii muscles of the chicken

In chicken, the main characteristic properties of muscle fibre types in slow anterior (ALD) and fast posterior (PLD) latissimus dorsii are acquired during post-hatching development. At day 4 it becomes possible to distinguish between alpha' and beta' fibre types in ALD muscle. At the same time, mATPase staining and NADH-TR activity permit recognition of alpha w and alpha R fibres within PLD muscle. During further development, muscle fibre typology progressively changes towards the adult slow and fast type. Chronic stimulation at a slow rhythm (5 Hz) of PLD prevents the change in relative proportions of alpha R and alpha W fibres within the muscle that occurs in normal post-hatching development and increases the number of beta R fibres. Moreover, oxidative activity is increased in all muscle fibre types following stimulation. In ALD muscle, chronic stimulation at a fast rhythm (40 Hz) results in a decrease in oxidative activity and inhibits the differentiation of alpha' and beta' muscle fibre types. This study demonstrates that in young chicken, the pattern of activity influences the differenciation of fibre types in slow and fast muscles.     

Endonuclease G: a (dG)n X (dC)n-specific DNase from higher eukaryotes.

An endonuclease activity (termed endonuclease G) that selectively cleaves DNA at (dG)n X (dC)n tracts has been partially purified from immature chicken erythrocyte nuclei. Sites where n greater than or equal to 9 are cleaved in a manner that resembles types II and III restriction nucleases. The nicking rate of the G-strand is 4- to 10-fold higher than that of the C-strand depending on the length of the (dG)n X (dC)n tract and/or nucleotide composition of the flanking sequences. Endonuclease G hydrolyzes (dG)24 X (dC)24 of supercoiled DNA in a bimodal way every 9-11 nucleotides, the maxima in one strand corresponding to minima in the opposite, suggesting that it binds preferentially to one side of the double helix. The nuclease produces 5' phosphomonoester ends and its activity is dependent on Mg2+ or Mn2+. The wide distribution and high relative activity of endonuclease G in a variety of tissues and species argues for a general role of the enzyme. The striking correlation between genetic instability and poly(dG) X poly(dC) tracts in DNA suggests that these sequences and endonuclease G are involved in recombination processes.     

Role of the reticuloendothelial system in the catabolism of low density lipoprotein in the rat

The role of the reticuloendothelial system (RES) in receptor-independent catabolism of human low density lipoprotein (h-LDL) was evaluated in the rat in vivo after blockade of its phagocytic activity with gadolinium chloride (GaCl3). After blockade of the RES with GaCl3, the recovery of [125I] h-LDL in the liver of 17 alpha-ethinyl oestradiol-treated rats (EE-rats), was decreased by 37 and 16%, 15 and 60 min after h-LDL injection, respectively. This decrease did not result in a decreased LDL degradation which represented 14 and 55% of the injected dose in the two groups of rats after 15 and 60 min respectively, both on GaCl3 and control rats. Contrasting with EE-rats, the catabolism of h-LDL in untreated rats is much slower and takes place essentially through a receptor-independent mechanism. Six hours after the injection of [125I] h-LDL, 64% of the dose was degraded. This proportion decreased to 45% after blockade of the RES phagocytic activity. This 30 percent difference represents the proportion of h-LDL catabolized by receptor-independent mechanisms present in the Küpffer and endothelial cells. We conclude from our study that in the normal rat, the parenchymal cells of the liver on the one hand and the Küpffer and endothelial cells on the other hand contribute 70 and 30% respectively to the receptor-independent catabolism of low density lipoproteins in vivo.     

Differential regulation by dexamethasone of glucocorticoid receptor messenger RNA concentrations in neuronal cultures derived from fetal rat hypothalamus and cerebral cortex

1. Differential regulation, by dexamethasone, of glucocorticoid receptor gene expression was studied in three different neuronal cultures derived from hypothalamus amygdala, and cerebral cortex. 2. Cellular glucocorticoid receptor (GR) mRNA concentration was measured by hybridization using a 32P-labeled RNA probe complementary to a 2.2-kb fragment of the glucocorticoid receptor mRNA. Changes in the amount of GR mRNA were evaluated in relation to the content of beta-actin mRNA. 3. In cells derived from either hypothalamus or cerebral cortex, we observed a complex pattern of GR mRNA concentrations which were characterized by cyclic variations of GR mRNA content during continuous treatment with dexamethasone for up to 72 hr. 4. In contrast to cells derived from the hypothalamus where a persistent 30-40% reduction in GR mRNA levels was seen for up to a least 72 hr, we observed, in cells derived from the cerebral cortex, a sustained increased (1.4-fold) of the GR mRNA at this same time interval.     

Lampetra (Eudontomyzon) gracilis,a synonym of Eudontomyzon danfordi

Synopsis Evidence is presented which suggests that the nonparasitic lamprey, Lampetra (Eudontomyzon) gracilis Kux, 1965, is conspecific with the parasitic lamprey Eudontomyzon danfordi Regan, 1911. The diagnostic characters of the holotype and of the non-type material of E. gracilis are features found in E. danfordi specimens in their second and final year of adult life, thereby making the former a junior synonym of the latter.     

Ionic transporting systems of skeletal muscle in relation with innervation and their involvement in myotonic diseases

Excitation-contraction coupling describes the series of events that begins with propagated action potential on the muscle fiber surface membrane and leads to the twitch contraction of the fiber. The generation of an action potential during excitation requires rapid sequential changes in membrane conductances of Na⁺, Ca²⁺, and K⁺ ions that depend upon the opening and closing of the respective channels. Myotonic disorders are inherited diseases whose clinical manifestations include electrophysiological signs such as increased excitability and delayed relaxation of the muscles after voluntary contraction. All these disorders appears to be due to an abnormality of the muscle itself since they persist after section or blocking of the motor nerve after curarization. Most experimental and clinical data suggest that human myotonia arises from genetically-induced structural and functional alterations of the muscle membrane. The purpose of this article is to focus on the more recent developments in the molecular and pharmacological analysis of cation transporting systems such as ionic channels and (Na⁺, K⁺) ATPase in myotonic disorders.Special issue dedicated to Dr. Lawrence Austin.