Cellular expression of interleukin 2 (IL-2) and its receptor (IL-2R, CD25) in lung tumours

In view of the unclear prognostic and diagnostic role of interleukin 2 (IL-2) and its receptor in human tumours, we examined the cellular expression of IL-2 and of the subunit α of its receptor (IL-2Rα, CD25) in relation to the proliferative activity of various subtypes of lung tumours. The immunocytochemical ABC technique was applied to archival tissue material of neuroendocrine lung tumours: lung carcinoids, including typical carcinoids (TC), atypical carcinoids (AC) and small-cell lung cancers (SCLC) and squamous cell lung cancers (non-small cell lung cancers, NSCLC). Expression of IL-2 was detected in all types of lung tumours. The highest frequency of IL-2 expression (93%) was noted and the most pronounced semi-quantitatively evaluated expression of IL-2 was detected in AC tumour cells. The expression was more pronounced as compared to neoplastic SCLC (p = 0.01) and NSCLC cells (p = 0.005). The results suggest a negative correlation between IL-2 expression and the proliferative activity of tumour cells (evaluated by expression of Ki-67) in AC. The frequency of detection of IL-2 receptor (IL-Rα, CD25) was the highest in NSCLC (94%). Semi-quantitative expression of IL-2R, like that of IL-2, also dominated in the group of atypical lung carcinoids but manifested a significant difference only as compared to typical carcinoids (p = 0.014). Within the groups of tumours studied no correlation could be detected between cellular expressions of IL-2 and IL-2R. Our results demonstrate variable expression of IL-2 and its receptor in various types of lung tumours, but no simple relationship could be detected between tissue expression of the markers and proliferative activity. Appraisal of the diagnostic and/or prognostic significance of the results requires further study

Dexamethasone as Abortive Treatment for Refractory Seizures or Status Epilepticus in the Inpatient Setting

Refractory seizures or status epilepticus (RS/SE) continues to be a challenge in the inpatient setting. Failure to abort a seizure with antiepileptic drugs (AEDs) may lead to intubation and treatment with general anesthesia exposing patients to complications, extending hospitalization, and increasing the cost of care. Studies have shown a key role of inflammatory mediators in seizure generation and termination. We describe 4 patients with RS/SE that was aborted when dexamethasone was added to conventional AEDs: a 61-year-old female with temporal lobe epilepsy who presented with delirium, nonconvulsive status epilepticus, and oculomyoclonic status; a 56-year-old female with history of traumatic left frontal lobe hemorrhage who developed right face and hand epilepsia partialis continua followed by refractory focal clonic seizures; a 51-year-old male with history of traumatic intracranial hemorrhage who exhibited left-sided epilepsia partialis continua; and a 75-year-old female with history of breast cancer who manifested nonconvulsive status epilepticus and refractory focal clonic seizures. All patients continued experiencing RS/SE despite first- and second-line therapy, and one patient continued to experience RS/SE despite third-line therapy. Failure to abort RS/SE with conventional therapy motivated us to administer intravenous dexamethasone. A 10-mg load was given (except in one patient) followed by 4.0- 5.2 mg q6h. All clinical and electrographic seizures stopped 3-4 days after starting dexamethasone. When dexamethasone was discontinued 1-3 days after seizures stopped, all patients remained seizure-free on 2-3 AEDs. The cessation of RS/SE when dexamethasone was added to conventional antiseizure therapy suggests that inflammatory processes are involved in the pathogenesis of RS/SE

Development of extracellular matrix supported 3D culture of renal cancer cells and renal cancer stem cells

Novel experimental conditions of cancer cell line culture have evolved throughout the recent years, with significantly growing interest in xeno-free, serum-free and three-dimensional culture variants. The choice of proper culture media may enable to mimic tumor microenvironment and promotion of cancer stem cells proliferation. To assess whether stem-like phenotype inducing media may be applied in renal cancer stem cell research, we performed a widespread screening of 13 cell culture media dedicated for mesenchymal cells, stem cells as well as mesenchymal stem cells. We have also screened extracellular matrix compounds and selected optimal RCC 3D—ECM supported culture model. Our results revealed that 786-O as well as HKCSCs cell line cultures in xeno-free media (NutriStem/StemXvivo) and laminin coated plates provide a useful tool in RCC cancer biology research and at the same time enable effective drug toxicity screening. We propose bio-mimic 3D RCC cell culture model with specific low-serum and xeno-free media that promote RCC cell viability and stem-like phenotype according to the tested genes encoding stemness factors including E-cadherin, N-cadherin, HIF1, HIF2, VEGF, SOX2, PAX2 and NESTIN

The legacy of cover crops on the soil habitat and ecosystem services in a heavy clay, minimum tillage rotation

Abstract Cover crops are grown as potential ways to improve soil fertility, soil structure, and biodiversity, while reducing weed/pest burdens. Yet, increased costs (in both time and fuel), farmer knowledge requirements, and yield uncertainty (green bridge effect and variable crop establishment) have led to hesitation among farmers. This study was conducted at the field scale (covering an area of nearly 20 hectares) to determine whether different cover crop mixtures affected soil properties and ecosystem services on a heavy clay soil. Measurements of soil chemistry, physics, biology, weed abundance, and subsequent crop performance were taken within a minimum tillage management system, across three cover crop mixtures (commonly sold to UK farmers). The cover crop mixtures included oats (Avena sativa), radish (Raphanus sativus), phacelia (Phacelia tanacetifolia), vetch (Vicia sativa), legumes, buckwheat (Fagopyrum esculentum) and a bare stubble control followed by a spring oat crop. Soil physics (penetrometer and bulk density) and chemistry (N, P, K, Mg, Ca, and organic matter) varied little across treatments, although there was significantly lower Mg in the cover crop including legumes and an increase in NO3 within this treatment. Soil biology and botanical composition were also assessed, monitoring earthworm and mesofauna abundance; and sown and unsown (weed) biomass. Epigeic earthworms were found to have significantly larger abundance in cover crop mixtures with radish present, although other meso- and macrofauna did not differ. Significant weed suppression was found during both the cover crop growing period and as a legacy in the subsequent crop, leading to significant yield increases and economic benefits in some treatments. Our study confirms that cover crops are providing benefits, even on heavy clay soils, including improvements in nutrient leaching risk reduction, weed suppression, and crop yield, coupled with wider ecosystem benefits. We therefore consider cover crops to have a role in sustainable management of arable rotations

A surface groove essential for viral Bcl-2 function during chronic infection in vivo

Antiapoptotic Bcl-2 family proteins inhibit apoptosis in cultured cells by binding BH3 domains of proapoptotic Bcl-2 family members via a hydrophobic BH3 binding groove on the protein surface. We investigated the physiological importance of the BH3 binding groove of an antiapoptotic Bcl-2 protein in mammals in vivo by analyzing a viral Bcl-2 family protein. We show that the gamma-herpesvirus 68 (gammaHV68) Bcl-2 family protein (gammaHV68 v-Bcl-2), which is known to inhibit apoptosis in cultured cells, inhibits both apoptosis in primary lymphocytes and Bax toxicity in yeast. Nuclear magnetic resonance determination of the gammaHV68 v-Bcl-2 structure revealed a BH3 binding groove that binds BH3 domain peptides from proapoptotic Bcl-2 family members Bax and Bak via a molecular mechanism shared with host Bcl-2 family proteins, involving a conserved arginine in the BH3 peptide binding groove. Mutations of this conserved arginine and two adjacent amino acids to alanine (SGR to AAA) within the BH3 binding groove resulted in a properly folded protein that lacked the capacity of the wild-type gammaHV68 v-Bcl-2 to bind Bax BH3 peptide and to block Bax toxicity in yeast. We tested the physiological importance of this v-Bcl-2 domain during viral infection by engineering viral mutants encoding a v-Bcl-2 containing the SGR to AAA mutation. This mutation resulted in a virus defective for both efficient reactivation of gammaHV68 from latency and efficient persistent gammaHV68 replication. These studies demonstrate an essential functional role for amino acids in the BH3 peptide binding groove of a viral Bcl-2 family member during chronic infection

Phonon and plasmon excitation in inelastic electron tunneling spectroscopy of graphite

The inelastic electron tunneling spectrum (IETS)of highly oriented pyrolitic graphite (HOPG) has been measured with scanning tunneling spectroscopy (STS) at 6K. The observed spectral features are in very good agreement with the vibrational density of states (vDOS) of graphite calculated from first principles. We discuss the enhancement of certain phonon modes by phonon-assisted tunneling in STS based on the restrictions imposed by the electronic structure of graphite. We also demonstrate for the first time the local excitation of surface-plasmons in IETS which are detected at an energy of 40 meV.Comment: PRB rapid communication, submitte

Contrasting crystal packing arrangements in triiodide salts of radical cations of chiral bis(pyrrolo[3,4-d])tetrathiafulvalenes

Crystal structures of six 1 : 1 triiodide salts of a series of enantiopure bis(pyrrolo[3,4-d])TTF derivatives, the first structures of radical cation salts reported for this bis(pyrrolo) donor system, show three different arrangements of triiodide ions, organised either in head-to-tail pairs, in infinite lines, or in a castellated arrangement. The complex crystal structures, obtained by electrocrystallisation, are influenced by the presence of solvent, for example changing an ABCABC packing arrangement to ABAB with inclusion of THF, as well as by the size of the chiral side chain

Systems Analysis for a Venus Aerocapture Mission

Previous high level analysis has indicated that significant mass savings may be possible for planetary science missions if aerocapture is employed to place a spacecraft in orbit. In 2001 the In-Space Propulsion program identified aerocapture as one of the top three propulsion technologies for planetary exploration but that higher fidelity analysis was required to verify the favorable results and to determine if any supporting technology gaps exist that would enable or enhance aerocapture missions. A series of three studies has been conducted to assess, from an overall system point of view, the merit of using aerocapture at Titan, Neptune and Venus. These were chosen as representative of a moon with an atmosphere, an outer giant gas planet and an inner planet. The Venus mission, based on desirable science from plans for Solar System Exploration and Principal Investigator proposals, to place a spacecraft in a 300km polar orbit was examined and the details of the study are presented in this paper

Cassini/Huygens Probe Entry, Descent, and Landing (EDL) at Titan Independent Technical Assessment

Starting in January 2004, the NESC has received several communications from knowledgeable technical experts at NASA expressing shared concerns (mainly at the Langley Research Center (LaRC) and Ames Research Center (ARC)) about Huygens mission success. It was suggested that NASA become more technically involved directly in the analysis of Huygens' entry, descent and landing (EDL) focusing on the parachute deployment trigger performance and the resultant effects on the operation of the parachute system, and the determination of the radiative heating environment at Titan by ESA and the corresponding thermal protection system (TPS) response. A NESC Team was formed and tasked to provide an independent assessment of these concerns. The results of that assessment are documented in this report