Cutaneous metastasis of occult hepatocellular carcinoma: a case report

BACKGROUND: Skin metastases from hepatocellular carcinoma (HCC) represented only 0.8% of all known cutaneous metastases in a recent large series. The most frequent site appears to be the head, but this fact has received little attention. An accurate cytologic diagnosis is extremely difficult in patients with unknown liver dysfunction. We report the cytologic features of a face metastasis from occult HCC. CASE: A 65-year-old woman presented with a mass in the right preauricular region of 2 months' duration. Her past medical history was noncontributory. Fine needle aspiration cytology was performed. Following the cytologic diagnosis, computed tomography revealed a 6-cm mass in the right lobe of the liver, portal vein thrombosis and involvement of the superior vena cava. The smears were very cellular. The most frequent pattern was trabecular with transmural endothelization. The cells had an epithelial appearance and polyhedral shape, exhibiting distinct borders. The nuclei were centrally placed, with a prominent nucleolus. The cytoplasm was granular. There were numerous atypical bare nuclei. Subsequent staining with antihepatocyte showed positivity in most tumor cells. The final diagnosis was metastatic HCC. CONCLUSION: HCCs should be considered in the differential diagnosis of carcinomas metastatic to the face, even in the absence of liver symptoms.     

Differential expression of the three multicopper oxidases from Myxococcus xanthus

Myxococcus xanthus is a soil bacterium that undergoes a unique life cycle among the prokaryotes upon starvation, which includes the formation of macroscopic structures, the fruiting bodies, and the differentiation of vegetative rods into coccoid myxospores. This peculiarity offers the opportunity to study the copper response in this bacterium in two different stages. In fact, M. xanthus vegetative rods exhibit 15-fold-greater resistance against copper than developing cells. However, cells pre-adapted to this metal reach the same levels of resistance during both stages. Analysis of the M. xanthus genome reveals that many of the genes involved in copper resistance are redundant, three of which encode proteins of the multicopper oxidase family (MCO). Each MCO gene exhibits a different expression profile in response to external copper addition. Promoters of cuoA and cuoB respond to Cu(II) ions during growth and development; however, they show a 10-fold-increased copper sensitivity during development. The promoter of cuoC shows copper-independent induction upon starvation, but it is copper up-regulated during growth. Phenotypic analyses of deletion mutants reveal that CuoB is involved in the primary copper-adaptive response; CuoA and CuoC are necessary for the maintenance of copper tolerance; and CuoC is required for normal development. These roles seem to be carried out through cuprous oxidase activity.     

Syntaxin and VAMP association with lipid rafts depends on cholesterol depletion in capacitating sperm cells

Sperm cells represent a special exocytotic system since mature sperm cells contain only one large secretory vesicle, the acrosome, which fuses with the overlying plasma membrane during the fertilization process. Acrosomal exocytosis is believed to be regulated by activation of SNARE proteins. In this paper, we identified specific members of the SNARE protein family, i.e., the t-SNAREs syntaxin1 and 2, and the v-SNARE VAMP, present in boar sperm cells. Both syntaxins were predominantly found in the plasma membrane whereas v-SNAREs are mainly located in the outer acrosomal membrane of these cells. Under non-capacitating conditions both syntaxins and VAMP are scattered in well-defined punctate structures over the entire sperm head. Bicarbonate-induced in vitro activation in the presence of BSA causes a relocalization of these SNAREs to a more homogeneous distribution restricted to the apical ridge area of the sperm head, exactly matching the site of sperm zona binding and subsequent induced acrosomal exocytosis. This redistribution of syntaxin and VAMP depends on cholesterol depletion and closely resembles the previously reported redistribution of lipid raft marker proteins. Detergent-resistant membrane isolation and subsequent analysis shows that a significant proportion of syntaxin emerges in the detergent-resistant membrane (raft) fraction under such conditions, which is not the case under those conditions where cholesterol depletion is blocked. The v-SNARE VAMP displays a similar cholesterol depletion-dependent lateral and raft redistribution. Taken together, our results indicate that redistribution of syntaxin and VAMP during capacitation depends on association of these SNAREs with lipid rafts and that such a SNARE-raft association may be essential for spatial control of exocytosis and/or regulation of SNARE functioning.     

Staying out in the cold: glacial refugia and mitochondrial DNA phylogeography in ancient European brown bears

Models for the development of species distribution in Europe typically invoke restriction in three temperate Mediterranean refugia during glaciations, from where recolonization of central and northern Europe occurred. The brown bear, Ursus arctos, is one of the taxa from which this model is derived. Sequence data generated from brown bear fossils show a complex phylogeographical history for western European populations. Long-term isolation in separate refugia is not required to explain our data when considering the palaeontological distribution of brown bears. We propose continuous gene flow across southern Europe, from which brown bear populations expanded after the last glaciation.     

Eradication of Helicobacter pylori for the prevention of peptic ulcer rebleeding

AIM: To evaluate the effect of Helicobacter pylori eradication on ulcer bleeding recurrence in a prospective, long-term study including more than 400 patients. METHODS: Patients with peptic ulcer bleeding were prospectively included. H. pylori infection was confirmed by rapid urease test, histology or (13)C-urea breath test. Several eradication regimens were used. Ranitidine 150 mg was administered daily until eradication was confirmed by breath test 8 weeks after completing eradication therapy. Patients with therapy failure received a second or third course of therapy. Patients with eradication success did not receive maintenance anti-ulcer therapy, and were controlled yearly with a repeated breath test. RESULTS: Four hundred and twenty-two patients were followed up for at least 12 months, with a total of 906 patient-years of follow up. Mean age was 59 years, and 35% were previous nonsteroidal anti-inflammatory drug (NSAID) users. Sixty-nine percent had duodenal, 24% gastric, and 7% pyloric ulcer. Recurrence of bleeding was demonstrated in two patients at 1 year (incidence: 0.22% per patient-year of follow up), which occurred after NSAID use in both cases. CONCLUSION: Peptic ulcer rebleeding does not occur in patients with complicated ulcers after H. pylori eradication. Maintenance anti-ulcer (antisecretory) therapy is not necessary if eradication is achieved.     

Environmental evaluation of single-use and reusable cups

Goal, Scope and Background The objective of the study was to determine the environmental effects of the resuable cup used during a major event (which took place in Barcelona, Universal Forum of Cultures, 2004), compared with a single-use cup of the same composition (polypropylene) but with different physical characteristics such as mass, shape and capacity. Methods To perform the environmental evaluations and the comparison of both types of cups, the SimaPro software developed and marketed by PRé Consultants was used. The environmental evaluation of the reusable cup was compared with that of a single-use cup using the LCA methodology [6]. The functional unit used was: ‘Serving 1000 liters of draught beverages’. The objective of the study was to find the minimum number of cycles the reusable cup has to do so that its environmental impact is smaller than that of the single-use cup. Results and Conclusions Taking into account all the hypotheses put forward, the study drew the conclusion that the minimum number of uses of the reusable cup necessary for it to have a smaller environmental impact than the single-use cup is 10. The contribution of each process taking part in the entire life cycle of the cups was also studied in detail. In the case of the single-use cup, the most important contribution to all the impact categories is due to the production of polypropylene and the fabrication of the cup, except for the heavy metals category where it is due to the management of the waste coming from the cup’s use. In the case of the reusable cup being used 10 times, the contribution to the different impact categories of the waste generated by the cup’s use is negligible compared to the contribution of the fabrication and washing processes. In addition, the washing process is the one which contributes most to the ozone layer depletion, heavy metals and carcinogens categories. As the number of uses of the reusable cup increases, the contribution to all the environmental impact categories decreases. However, this reduction is not as significant for the ozone layer depletion, heavy metals and carcinogens categories. This is due to the washing process and the fact that the electrical consumption associated with it increases with the number of washings and, consequently, of uses. Recommendations and Perspectives From the environmental point of view, the reusable cup must be used at least 10 times to have less impact than the single-use cup. This is mainly due to the higher weight of the reusable cup and, therefore, the greater amount of raw material needed for its fabrication. If the LCA methodology had been introduced during the design of the reusable cup, its weight would have been lower. This modification would have resulted in a reduction of the environmental impact associated with the use of the reusable cup and, consequently, a smaller number of uses would have been necessary to attain the same level of impact as the single-use cup.     

Modelling the niche for a marine vertebrate: a case study incorporating behavioural plasticity,proximate threats and climate change

The integration of satellite telemetry, remotely sensed environmental data, and habitat/environmental modelling has provided for a growing understanding of spatial and temporal ecology of species of conservation concern. The Republic of Cape Verde comprises the only substantial rookery for the loggerhead turtle Caretta caretta in the eastern Atlantic. A size related dichotomy in adult foraging patterns has previously been revealed for adult sea turtles from this population with a proportion of adults foraging neritically, whilst the majority forage oceanically. Here we describe observed habitat use and employ ecological niche modelling to identify suitable foraging habitats for animals utilising these two distinct behavioural strategies. We also investigate how these predicted habitat niches may alter under the influence of climate change induced oceanic temperature rises. We further contextualise our niche models with fisheries catch data and knowledge of fisheries ‘hotspots’ to infer threat from fisheries interaction to this population, for animals employing both strategies. Our analysis revealed repeated use of coincident oceanic habitat, over multiple seasons, by all smaller loggerhead turtles, whilst larger neritic foraging turtles occupied continental shelf waters. Modelled habitat niches were spatially distinct, and under the influence of predicted sea surface temperature rises, there was further spatial divergence of suitable habitats. Analysis of fisheries catch data highlighted that the observed and modelled habitats for oceanic and neritic loggerhead turtles could extensively interact with intensive fisheries activity within oceanic and continental shelf waters of northwest Africa. We suggest that the development and enforcement of sustainable management strategies, specifically multi‐national fisheries policy, may begin to address some of these issues; however, these must be flexible and adaptive to accommodate potential range shift for this species.     

Tor1, Sch9 and PKA downregulation in quiescence rely on Mtl1 to preserve mitochondrial integrity and cell survival

Here we show that Mtl1, member of the cell wall integrity pathway of Saccharomyces cerevisiae, plays a positive role in chronological life span (CLS). The absence of Mtl1 shortens CLS and causes impairment in the mitochondrial function. This is reflected in a descent in oxygen consumption during the postdiauxic state, an increase in the uncoupled respiration and mitochondrial membrane potential and also a descent in aconitase activity. We demonstrate that all these effects are a consequence of signalling defects suppressed by TOR1 (target of rapamycin) and SCH9 deletion and less efficiently by Protein kinase A (PKA) inactivation. Mtl1 also plays a role in the regulation of both Bcy1 stability and phosphorylation, mainly in response to glucose depletion. In postdiauxic phase and in conditions of glucose depletion, Mtl1 negatively regulates TOR1 function leading to Sch9 inactivation and Bcy1 phosphorylation converging in PKA inhibition. Slt2/Mpk1 kinase partially contributes to Bcy1 phosphorylation, although additional targets are not excluded. Mtl1 links mitochondrial dysfunction with TOR and PKA pathways in quiescence, glucose being the main signalling molecule.