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.     

Digest: The contribution of historical climate events in shaping the modern latitudinal diversity gradient of ancient reptiles

It is recognized that biodiversity changes across the planet latitudinally; however, the timing of and reasons for diversity loss at higher latitudes are not well understood. Meseguer and Condamine investigate phylogenies and fossil evidence of reptilian species and determine that global warming and cooling events allowed asymmetric extinction and dispersion across latitudes, suggesting a hypothesis where climate profoundly shapes the latitudinal diversity gradient in certain taxa.     

Simultaneous radioimmunoassay of progesterone, androst-4-enedione, pregnenolone, dehydroepiandrosterone and 17-hydroxyprogesterone in specific regions of human brain

Simultaneous determination of progesterone, androst-4-enedione, pregnenolone, dehydroepiandrosterone (DHEA) and 17-hydroxyprogesterone has been developed for human cerebral tissue. Before immunoassay, steroids were separated on a Celite column with propylene glycol as stationary phase with hexane containing increasing proportions of dichloromethane as mobile phase. This system allowed separation of steroids of similar polarity, especially of pregnenolone and progesterone. The brain regions studied cortex (prefrontal, parietal and temporal), cerebellum and corpus callosum, were obtained after autopsy from 9 women and 1 man between 76 and 93 years of age. Steroids were found in all regions. The overall concentrations expressed in nmol/kg of tissue were: 10.1, 7.6, 120.7, 19.6 and 10.4 respectively, for progesterone, androst-4-enedione, pregnenolone, dehydroepiandrosterone and 17-hydroxyprogesterone, corresponding to 7.3, 4.9, 74, 6.5 and 9.2 times the plasma levels. These very high concentrations, not previously described in human brain tissue, pose the question of the existence of local biosynthetic pathways independent of the peripheral endocrine gland system as well as that of progressive accumulation of steroids over a lifetime. Concentrations of each steroid in each subject varied little among the various brain regions studied, but there was much variation among the subjects with respect to the concentrations of a given steroid.     

Influence of a prolonged tamoxifen administration on steroidogenesis by incubated rat testes

Tamoxifen was administered i.m. for 9 days to adult male rats in a daily dose of 100 micrograms or 1 mg. The treatment resulted in a significant reduction of the plasma levels of testosterone and LH, without modification of the plasma levels of FSH and of the testes weight. Upon incubation, the testes from the tamoxifen-treated rats produced less testosterone and 7 alpha-hydroxytestosterone, but metabolized [4-14C]testosterone in the same way as the control animals. Small doses of hCG (0.5 i.u. for 9 days) were unable to modify the tamoxifen effect on the testicular function, while tamoxifen significantly inhibited the increase of the plasma levels of testosterone induced by the administration of moderate doses of hCG (1.5 i.u. or 2.5 i.u. for 9 days) to hypophysectomized rats. Tamoxifen treatment, however, did not modify significantly the reactivity of the testes towards high doses of hCG (10 i.u.), administered either 2 h before sacrifice or for 9 days. It is concluded that a prolonged administration of tamoxifen in the rat has, besides an indirect effect resulting from a decrease of the LH levels, a direct inhibitory influence on the testicular testosterone formation, which can be reversed by high doses of hCG.     

Influence of neonatal androgenization on the testicular steroidogenesis in the adult rat

The in vitro testicular steroidogenesis of male rats, androgenized on the third postnatal day by a single injection of 1 mg testosterone propionate, was investigated when the animals were 100 days old. The neonatal androgenization resulted in a 25% lower testes weight, significantly increased plasma levels of FSH (P less than 0.01) and LH (P less than 0.02), and normal levels of testosterone. Although the testes were hypotrophic, the incubation of the testes pairs yielded the same amounts of testosterone, 7 alpha-hydroxytestosterone and 5 alpha-androstane-(3 alpha + 3 beta), 17 beta-diol as in the control animals. However, the steroidogenic response to an acute hCG stimulation was reduced. From incubations of testes homogenates with various labelled steroid precursors it could be inferred that the activity of the 17 alpha-hydroxylase, the 3 beta-hydroxysteroid dehydrogenase-isomerase and the 17 beta-hydroxysteroid dehydrogenase, expressed per unit of incubated protein, was significantly increased in the testes of the androgenized rats. These data indicate that the basal steroidogenesis in neonatally androgenized male rats is maintained by an increased synthesis per unit of tissue, possibly under influence of an increased gonadotrophic stimulus, but that the maximum steroidogenic capacity is reduced.     

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.