Glycoprotein IIb/IIIa receptor antagonists in acute myocardial infarction and primary coronary stenting: Not always effective

Glycoprotein IIb/IIIa antagonists have been shown to be effective in reducing thrombotic complications prior to high-risk coronary interventions. Some studies have reported improved coronary flow after abciximab in slow or no-reflow phenomenon. We report a case in which abciximab did not clear the thrombotic occlusion or restore artery flow. Further studies are needed into the refractory no-flow phenomenon.     

Somatostatin interferes with thyrotropin-induced G1-S transition mediated by cAMP-dependent protein kinase and phosphatidylinositol 3-kinase. Involvement of RhoA and cyclin E x cyclin-dependent kinase 2 complexes

cAMP-mediated cell proliferation is a complex process that involves multiple pathways. Using a cAMP-dependent cell system, FRTL-5 thyroid cells, we have previously demonstrated the existence of a precise autocrine loop in the control of cell proliferation that involves the positive effector thyrotropin (TSH) and the general inhibitor somatostatin. In search of the regulatory mechanisms responsible for the TSH and somatostatin control of cell proliferation, we analyzed the cell cycle regulatory proteins and the cellular pathways involved in the action of both signals. The results show that specific inhibition of cAMP-dependent protein kinase (PKA) and phosphatidylinositol (PI) 3-kinase blocks independently TSH-induced FRTL-5 cell proliferation and that somatostatin interferes with both signals. Each pathway activates different proteins required for G(1)/S progression. Thus, PKA is responsible for the TSH-induction of 3-hydroxy-3-methylglutaryl-CoA reductase mRNA levels, RhoA activation, and down-regulation of p27(kip1). These correlated events are necessary for FRTL-5 cell proliferation after TSH stimulation. Moreover, TSH through PKA pathway increases cyclin-dependent kinase 2 levels, whereas PI 3-kinase signaling increases cyclin E levels. Together, both pathways finally converge, increasing the formation and activation of cyclin E x cyclin-dependent kinase 2 complexes and the phosphorylation of the retinoblastoma protein, two important steps in the transition from G(1) to S phase in growth-stimulated cells. Somatostatin exerts its antiproliferative effect inhibiting more upstream the TSH stimulation of PKA and PI 3-kinase, interfering with the TSH-mediated increases of intracellular cAMP levels by inactivation of adenylyl cyclase activity. Together, these results suggest the existence of a PKA-dependent pathway and a new PKA-independent PI 3-kinase pathway in the TSH/cAMP-mediated proliferation of FRTL-5 thyroid cells.     

Binding interactons of collagen I, laminin and fibronectin with immobilized Escherichia coli 0157:H7 using a surface plasmon resonance biosensor

Real-time interactions of collagen I, fibronectin, laminin, hyaluronic acid and chondroitin sulfate with immobilized Escherichia coli O157:H7 cells were studied with a surface plasmon resonance biosensor. Results showed that collagen I and laminin bound to the E.coli surface but fibronectin had very low binding while hyaluronic acid and chondroitin sulfate had no detectable interaction. Calcium ion inhibited laminin binding but enhanced collagen I binding. This research provides a model system to study the interactions of bacterial cells with extracellular matrix components. © Rapid Science Ltd. 1998     

Nitrogen distribution and leaf area indices in relation to photosynthetic nitrogen use efficiency in savanna grasses

Leaf photosynthetic characteristics, distribution patterns of nitrogen content per unit leaf area (n_L) and leaf area production per unit n_Lwere measured in natural stands of a C₄ grass (Hyparrhenia rufa) from the seasonal savannas and of a C₄grass (Paspalum fasciculatum) and two C₃grasses (Leersia hexandra and Hymenachne amplexicaulis) from the flooded savannas in central Venezuela. Daily rates of canopy photosynthesis (P_cD) as well as the optimal leaf area production per unit n_Lat which P_cDfor a given total amount of nitrogen in the canopy (i.e., canopy-PNUE) is maximized were also calculated. The C₃and C₄species from the flooded savannas had similar light saturated rates of photosynthesis per unit n_L(i.e. leaf-PNUE) and similar canopy-PNUEs which was in strong contrast with previous studies. Especially H. rufa but also L. hexandra and H. amplexicaulis had leaf- and canopy-PNUEs which were considerably higher than the values calculated for most other species with the same photosynthetic pathway (i.e., C₃or C₄). In contrast to previous studies, differences in the light gradient in the canopy between stands only partially explained differences in N distribution. Measured leaf area indices were greater and the average n_L values were consequently smaller than the calculated optima. There was, however, a very strong linear correlation between the optimal and actual average n_Lindicating that even though the model overestimated average n_L, it did predict the differences in leaf area production per unit nitrogen – the inverse average n_L– very well. This result strongly indicates that leaf area production per unit of leaf nitrogen increases with leaf-PNUE and decreases with the extinction coefficient for light. Grass species from seasonal savannas have extremely high leaf-PNUEs and thus optimally produce large amounts of leaf area per unit n_L. This helps explain how stands of these species may have high leaf area indices and achieve high photosynthetic productivity despite the very low nutrient availability at which they grow.     

Subterranean rodents of the genus Ctenomys (Caviomorpha, Ctenomyidae) follow the converse to Bergmann's rule

Aim We analysed body‐size variation in relation to latitude, longitude, elevation and environmental variables in Ctenomys (tuco‐tucos), subterranean rodents in the Ctenomyidae (Caviomorpha). We tested the existence of inter‐ and intraspecific size clines to determine if these rodents follow Bergmann's rule, to compare intra‐ and interspecific size trends and to assess the relevance of the subterranean lifestyle on these trends. Location South America, south of 15° latitude. Methods This paper is based on 719 specimens of tuco‐tucos from 133 localities of Argentina, Bolivia, Chile, Paraguay, Peru and Uruguay, representing 47 named species and 32 undescribed forms. Intraspecific analyses were performed for Ctenomys talarum Thomas, 1898 and the Ctenomys perrensi Thomas, 1896 species complex. Head and body length and weight were used for estimating body size. Geographical independent variables included latitude, longitude and altitude. Environmental independent variables were mean minimal and maximal monthly temperature, mean annual temperature, mean minimal and maximal precipitation, and total annual precipitation. To estimate seasonality, the annual variability of the climatic factors was calculated as their coefficients of variation and the difference between maximum and minimum values. Mean annual actual evapotranspiration (AET), and mean annual, January (summer) and July (winter) potential evapotranspiration (PET) values were also calculated for each locality, as well as annual, summer and winter water balance (WB). Statistical analyses consisted of simple and multiple regression and nonparametric correlation. Results Body size of Ctenomys decreases interspecifically from 15°00′ S to 48°15′ S and from 56°33′ W to 71°46′ W, and is positively correlated with ambient temperature and precipitation. The best predictors of body size according to multiple regression analyses were mean annual temperature, the difference between mean maximum and minimum annual temperatures, annual PET, the difference between summer and winter PET, and annual and winter water balance. These patterns are repeated, but not identically, at a smaller geographical scale within the species C. talarum and the superspecies C. perrensi. Main conclusions Tuco‐tucos follow the converse to Bergmann's rule at the interspecific level. At the intraspecific level some parallel trends were observed, but the smaller scale of these analyses, involving a very reduced variation of environmental factors, necessitates caution in interpreting results. The subterranean lifestyle probably insulates these rodents from the external temperature. The observed latitudinal body‐size gradients are more probably related to seasonality, ambient energy, primary productivity and/or intensity of predation.     

The Expression of the Ubiquitin Ligase SIAH2 (Seven In Absentia Homolog 2) Is Increased in Human Lung Cancer

Objectives

Lung cancer is the leading cause of cancer-related deaths worldwide. Overall 5-year survival has shown little improvement over the last decades. Seven in absentia homolog (SIAH) proteins are E3 ubiquitin ligases that mediate proteasomal protein degradation by poly-ubiquitination. Even though SIAH proteins play a key role in several biological processes, their role in human cancer remains controversial. The aim of the study was to document SIAH2 expression pattern at different levels (mRNA, protein level and immunohistochemistry) in human non-small cell lung cancer (NSCLC) samples compared to surrounding healthy tissue from the same patient, and to analyse the association with clinicopathological features.

Materials and Methods

One hundred and fifty-two samples from a patient cohort treated surgically for primary lung cancer were obtained for the study. Genic and protein expression levels of SIAH2 were analysed and compared with clinic-pathologic variables.

Results

The present study is the first to analyze the SIAH2 expression pattern at different levels (RNA, protein expression and immunohistochemistry) in non-small cell lung cancer (NSCLC). We found that SIAH2 protein expression is significantly enhanced in human lung adenocarcinoma (ADC) and squamous cell lung cancer (SCC). Paradoxically, non-significant changes at RNA level were found, suggesting a post-traductional regulatory mechanism. More importantly, an increased correlation between SIAH2 expression and tumor grade was detected, suggesting that this protein could be used as a prognostic biomarker to predict lung cancer progression. Likewise, SIAH2 protein expression showed a strong positive correlation with fluorodeoxyglucose (2-deoxy-2(¹⁸F)fluoro-D-glucose) uptake in primary NSCLC, which may assist clinicians in stratifying patients at increased overall risk of poor survival. Additionally, we described an inverse correlation between the expression of SIAH2 and the levels of one of its substrates, the serine/threonine kinase DYRK2.

Conclusions

Our results provide insight into the potential use of SIAH2 as a novel target for lung cancer treatment.     

Differences in Type I Interferon Signaling Antagonism by Dengue Viruses in Human and Non-Human Primate Cell Lines

Background/ObjectivesIn vitro studies have shown that dengue virus (DENV) can thwart the actions of interferon (IFN)-α/β and prevent the development of an antiviral state in infected cells. Clinical studies looking at gene expression in patients with severe dengue show a reduced expression of interferon stimulated genes compared to patients with dengue fever. Interestingly, there are conflicting reports as to the ability of DENV or other flaviviruses to inhibit IFN-α/β signaling.ConclusionsThe ability of DENVs to inhibit IFN-α/β signaling is conserved. Although some variation in the inhibition was observed, the moderate differences may be difficult to correlate with clinical outcomes. DENVs were unable to inhibit pSTAT1 in NHP cell lines, but their ability to inhibit pSTAT1 in primary Rhesus macaque dendritic cells suggests that this may be a cell specific phenomena or due to the transformed nature of the cell lines.