bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemical behaviour of sphalerite and arsenopyrite in hydrothermal and metamorphic environments
Authors: Scott S. D.
Published: December 2006

Examples of application of equilibria in the systems Fe-Zn-S, Cu-Fe-Zn-S, Fe-As-S, and Fe-Zn-As-S are drawn from modern sulphide-forming hydrothermal vents on the East Pacific Rise, from ancient vein deposits and from metamorphosed sulphide ores. The ZnS content (1.2 and 1.3 mole %) of Cu-Fe-S intermediate solid solution (iss) from the sea-floor deposits gives temperatures of equilibration of 331° and 335 °C from experimental curves, in excellent agreement with the 350 °C expected from actual measurement of the hot springs. Heterogeneities in sphalerite in these deposits do not necessarily represent disequilibrium during deposition but can be explained simply by small fluctuations in aS2. Diagrams of log aS2vs. 1000/T, K for sphalerite and arsenopyrite are useful for estimating temperature and activity of sulphur in hydrothermal or metamorphosed deposits provided that equilibrium can be demonstrated and the systems are properly buffered.

The sphalerite geobarometer has had wide applications, some successful (mostly vein deposits) and some not (particularly metamorphosed ores in which chalcopyrite is in contact with sphalerite). Compositions of sphalerites which are totally enclosed within metablastic pyrites represent preserved high P-T equilibria which have been isolated from further reaction during subsequent retrograde conditions by the inert encapsulating pyrite and may provide more reliable estimates of pressure.
Pyrrhotine-pentlandite ore textures: a mechanistic approach
Authors: Kelly D. P. , Vaughan D. J.
Published: December 2006

The kinetics and mechanisms of pentlandite [(Fe,Ni)9S8] exsolution from the monosulphide solid solution [or MSS (Fe,Ni)1−xS] have been studied by synthesis and annealing experiments in part of the Fe-Ni-S system particularly relevant to sulphide nickel orebodies. This experimental work has been combined with the examination of the compositions and textures of pyrrhotine-pentlandite intergrowths from a variety of ore deposits. Isothermal annealing of MSS compositions with varying M:S and Fe:Ni ratios at 400 °C shows the formation of a sequence of textures which depend for their full development chiefly on initial M:S ratio and annealing time. The full sequence of textures starts with heterogeneous nucleation of pentlandite at MSS grain boundaries, the growth of these blebs to form ‘rims’, nucleation of finer bladed particles arranged ‘en échelon’ along fractures, and, finally, homogeneous nucleation of fine orientated pentlandite lamellae. Using the information from the annealing experiments, the inter-growths produced by cooling in the natural ores are interpreted using a simplified Time-Temperature-Transformation Model.
The chemistry, reflectance, and cell size of the erlichmanite (OsS2)-laurite (RuS2) series
Authors: Bowles J. F. W. , Atkin D. , Lambert J. L. M. , Deans T. , Phillips R.
Published: December 2006

Microprobe analyses of members of the erlichmanite-laurite series from Guma Water and Senduma, Sierra Leone and Tanah Laut, Borneo, indicate that complete solid solution is possible between OsS2 and RuS2 with considerable substitution of Os and Ru by Ir, Rh, and Pt. The cell size of the erlichmanite from Guma Water is a = 5.6183±0.0003 Å at a composition (Os0.61Ru0.30Ir0.06Rh0.03)Σ0.93S2 whilst the laurite from Senduma has a composition of (Ru0.88Os0.05Ir0.04 Rh0.03)Σ0.93S2 and a cell size of a = 5.6089±0.0005 Å. Substitution of Os for Ru provides the predominant cause of the variation of cell size. Substitution by other elements of the platinum group appears to produce little effect on cell size and is presumably controlled by genesis rather than considerations of crystal chemistry or structure. The recorded analyses for these elements indicate a pre-dominance of Ir over Rh for members of the series containing more than about 15% of the laurite molecule. For the remainder of the series Rh is more important than Ir. The reflectance in air and oil of the members of the series from Sierra Leone and Borneo are presented and the microhardness of the erlichmanite from Guma Water shown to be 1854 kg/mm2. This is the first report of laurite from Senduma, Sierra Leone.
The Witwatersrand pyrites and metamorphism
Authors: Hallbauer D. K. , Gehlen K. von
Published: December 2006

Evidence obtained from morphological and extensive trace element studies, and from the examination of mineral and fluid inclusions in Witwatersrand pyrites, shows three major types of pyrite: (i) detrital pyrite (rounded pyrite crystals transported into the depositional environment); (ii) synsedimentary pyrite (round and rounded aggregates of fine-grained pyrite formed within the depositional environmen); and (iii) authigenic pyrite (newly crystallized and/or recrystallized pyrite formed after deposition). The detrital grains contain mineral inclusions such as biotite, feldspar, apatite, zircon, sphene, and various ore minerals, and fluid inclusions with daughter minerals. Most of the inclusions are incompatible with an origin by sulphidization. Recrystallized authigenic pyrite occurs in large quantities but only in horizons or localities which have been subjected to higher temperatures during the intrusion or extrusion of younger volcanic rocks. Important additional findings are the often substantial amounts of pyrite and small amounts of particles of gold found in Archaean granites (Hallbauer, 1982) as possible source rocks for the Witwatersrand detritus. Large differences in Ag and Hg content between homogeneous single gold grains within a hand specimen indicate a lack of metamorphic homogenization. The influence of metamorphism on the Witwatersrand pyrites can therefore be described as only slight and generally negligible.
Deformation and recrystallization of pyrite
Authors: McClay K. R. , Ellis P. G.
Published: December 2006

A detailed study of pyrite in a number of metamorphosed, stratiform, sediment-hosted Pb-Zn deposits has shown the importance of cataclastic deformation, pressure-solution, and grain growth in the deformation and textural development of pyrite. Primary depositional or early diagenetic microstructures are preserved in pyritic ores deformed or metamorphosed at grades up to mid-upper greenschist facies, whereas at higher temperatures only metablastic or annealed pyrite textures are found. Brittle deformation is found at all metamorphic grades and is favoured by coarse grain-sizes. Pressure-solution is a major deformation mechanism in fine-grained pyritic ores in low-grade metamorphic environments. Grain growth and annealing dominate at higher metamorphic temperatures and are likely to have obliterated any evidence of deformation by dislocation processes. Significant macroscopic ductility of fine-grained pyritic ores in low-grade environments may be accounted for by a combination of pressure-solution, grain boundary sliding, and cataclastic flow.
Silver mineralization at Sark's Hope mine, Sark, Channel Islands
Authors: Ixer R. A. , Stanley C. J.
Published: December 2006

Sark's Hope silver-lead lode, which was mined during the 1830s and 1840s cuts a Late Precambrian granite at the southernmost point of the island of Sark. The primary ore assemblage is pyrite, galena, chalcopyrite, tennantite, tetrahedrite, sphalerite, marcasite, arsenopyrite, pyrrhotine, bravoite, enargite, and the silver minerals pyrargyrite, pearceite, polybasite, and acanthite. Gangue minerals are hematitic quartz, calcite, and illite. Alteration products include chalcosine, covelline, blaubleibender covelline, limonite, malachite, azurite, cerussite, and anglesite. The generalized paragenesis is of early Fe, Co, Ni, As, and S species and later minerals of Pb, Cu, Ag, Zn, Fe, As, Sb, and S. The earliest alteration products are copper sulphides; these are followed by lead and copper carbonates and sulphates, and hydrated iron and manganese oxides. Growth zoning is a common feature of many of the ore minerals, and electron microprobe analysis shows that this is sometimes related to compositional differences. Tetrahedrite and tennantite, particularly, exhibit a wide range of compositions.
Sb-rich rutile in the manganese concentrations at St. Marcel-Praborna, Aosta Valley, Italy: petrology and crystal-chemistry
Authors: Smith David C. , Perseil Elena-Adriana
Published: December 2006

The petrographical, crystal-chemical and petrogenetical aspects of rutile rich in antimony (up to 33.75 wt.% Sb2O5; equal to 0.2 Sb5+ per O = 2) from St. Marcel-Praborna in the Aosta Valley, Italy, were re-examined. These compositions occur in two different petrographical environments (within the rock matrix or as microinclusions within Sb-rich titanite) in the manganese concentrations at this locality. The new data confirm our earlier hypothesis that two distinct petrogenetical/crystal-chemical processes both occurred: 1. Sb-metasomatism of pre-existing Sb-free rutile inclusions; and 2. creation of neoblastic Sb-rich rutile by the expulsion of Ti from pre-existing Sb-free titanite being metasomatized by Sb to form Sb-rich titanite. In the literature, Sb in minerals is variably considered as being trivalent and/or pentavalent. This work demonstrates that within rutile it is entirely Sb5+, substituting for Ti4+ by the following heterovalent cation exchange mechanism which is also the dominant one in the host Sb-rich titanite: 2 viR4+ = viR3+ + viR5+, where viR3+ = (Al,Cr,Mn,Fe)3+. A near-perfect correlation of ΣR5+vs. ΣR3+ (r > 0.98) is perturbed only by the presence of trace amounts of Ca2+, Sr2+ and Ba2+. Traces of Mn4+, Si4+ and/or (OH)− might also be present. These alkaline earth cations are the largest cations ever recorded in the rutile structure and are seemingly too large to occupy normal octahedral sites. The cation exchange mechanism involved might be that found in the ‘trirutile’ mineral group: 3 viR4+ = viR2+ + 2 viR5+. Alternatively these large divalent cations may be situated in the lozenge-shaped tunnels of the rutile structure, by analogy with other large cations occupying the wider subrectangular tunnels in the analogous cryptomelane/hollandite/priderite, romanéchite and todorokite mineral groups. This leads to a possible new cation exchange mechanism for the rutile structure: 2 viR4+ + tunelvacant = 2 viR3+ + tunnelR2+.
Crystal structure refinement of miargyrite, AgSbS2
Authors: Smith Joseph V. , Pluth Joseph J. , Han Shao-Xu
Published: December 2006

Miargyrite is the low-temperature monoclinic derivative of a high temperature cubic galena/halite structure. The essential features of its crystal structure (Knowles, 1959) were confirmed, but the details of the bonding changed [new space group C121; a 12.824(1), b 4.4060(3), c 13.193(1) Å, β 98.567(6)°]. The octahedral connectivity of galena/halite is severely distorted: Ag(1), 2S each at 2.53, 2.66 & 3.39 Å; Ag(2), 2 each at 2.54, 2.62 and 3.44; Ag(3), 2.38, 2.40, 3.05, 3.05, 3.53, 3.58; Sb(1), 2.45, 2.50, 2.51, 3.22 3.28, 3.41; Sb(2), 2.45, 2.50, 2.51, 3.22, 3.28, 3.41. The short distances define the following coordinations: very distorted tetrahedral Ag(1) and (2); near-linear Ag(3) at 178.9(2)° trigonal-pyramidal Sb(1) and (2) at 92.0, 93.6 and 96.8°. The ten shortest S-S distances range from 3.61 to 3.77 Å.
Crystal structure of austinite, CaZn(AsO4)OH
Authors: Clark Lori A. , Pluth Joseph J. , Steele Ian , Smith Joseph V. , Sutton Stephen R.
Published: December 2006

Austinite belongs to the adelite mineral group of calcium and lead arsenates, and has the conichalcite/descloizite type of crystal structure. The crystal structure of nearly pure austinite, CaZn(AsO4)OH, was redetermined (R = 0.014) and the absolute configuration identified. The space group P212121 and cell parameters a 7.5092(8), b 9.0438(9), c 5.9343(8) Å match previous data. Zinc octahedra share edges to form chains parallel to c. Arsenic tetrahedra share vertices with the Zn octahedra to generate a compact framework. Calcium square antiprisms share edges to make chains parallel to a that occupy the channels in the zinc-arsenic framework.
The crystal structure of mawbyite, PbFe2(AsO4)2(OH)2
Authors: Kharisun  , Taylor M. R. , Bevan D. J. M. , Rae A. D. , Pring A.
Published: December 2006

The crystal structure of mawbyite, PbFe2(AsO4)2(OH)2 has been refined. The mineral is monoclinic, C2/m with a = 9.066(4), b = 6.286(3) c = 7.564(3) Å, β = 114.857(5)°, Z = 2; the structure has been refined to a conventional R = 4.3% using 361 observed reflections [I> 3σ(I)]. The structure contains chains of edgesharing Fe(O,OH)6 octahedra which are linked by AsO4 tetrahedra and Pb atoms in distorted square antiprismatic co-ordination. The hydrogen bonding network in the structure has been modelled using bond valence calculations. Mawbyite is confirmed to be isostructural with tsumcorite and dimorphous with carminite and the relationship between these two structures is discussed.
Al-rich warwickite from lnglefield Land, North-West Greenland
Authors: Uitterdijk Appel Peter W.
Published: December 2006

Warwickite constitutes about 5% of an outcrop of metamorphosed ultramafic rocks of Precambrian age in North-West Greenland. It occurs as slender grains, several millimetres long, and in anhedral grains up to 5 mm in size, together with forsterite, pleonaste, phlogopite, magnetite ± tourmaline. Post-metamorphic alteration of warwickite produced a network of boron-rich minerals and magnetite. The warwickite, containing up to 9.72% Al2O3, displays a significantly different chemical composition from warwickite elsewhere, such as that in recrystallized limestones from the type locality Warwick, New York, and in lamproitic and carbonatite-like rocks at Jumilla, Spain.
Igneous graphite in enstatite chondrites
Authors: Rubin Alan E.
Published: December 2006

Igneous graphite, a rare constituent in terrestrial mafic and ultramafic rocks, occurs in three EH and one EL enstatite chondrite impact-melt breccias as 2–150 µm long euhedral laths, some with pyramidal terminations. In contrast, graphite in most enstatite chondrites exsolved from metallic Fe-Ni as polygonal, rounded or irregular aggregates. Literature data for five EH chondrites on C combusting at high temperatures show that Abee contains the most homogeneous C isotopes (i.e. δ13C = −8.1 ± 2.1‰); in addition, Abee's mean δ13C value is the same as the average high-temperature C value for the set of five EH chondrites. This suggests that Abee scavenged C from a plurality of sources on its parent body and homogenized the C during a large-scale melting event. Whereas igneous graphite in terrestrial rocks typically forms at relatively high pressure and only moderately low oxygen fugacity (e.g., ∼ 5 kbar, logfO2 ∼ −10 at 1200°C), igneous graphite in asteroidal meteorites formed at much lower pressures and oxygen fugacities.
Plasmacytoid DCs regulate recall responses by rapid induction of IL-10 in memory T cells
Authors: Kvale Espen O. , Fløisand Yngvar , Lund-Johansen Fridtjof , Rollag Halvor , Farkas Lorant , Ghanekar Smita , Brandtzaeg Per , Jahnsen Frode L. , Olweus Johanna
Published: December 2006

Dendritic cells (DCs) are believed to regulate T cell-mediated immunity primarily by directing differentiation of naive T cells. Here, we show that a large fraction of CD4+ memory cells produce IL-10 within the first hours after interaction with plasmacytoid DCs (PDCs). In contrast, CD11c+ DCs induce IFN-γ and little IL-10. IL-10–secreting T cells isolated after 36 hours of culture with PDCs suppressed antigen-induced T-cell proliferation by an IL-10–dependent mechanism, but were distinct from natural and type 1 regulatory T cells. They proliferated strongly and continued to secrete IL-10 during expansion with PDCs, and after restimulation with immature monocyte-derived DCs or CD11c+ DCs. The IL-10–producing T cells acquired the ability to secrete high levels of IFN-γ after isolation and subsequent coculture with PDCs or CD11c+ DCs. Compared to CD11c+ DCs, PDCs were superior in their ability to selectively expand T cells that produced cytokines on repeated antigenic challenge. The DC-dependent differences in cytokine profiles were observed with viral recall antigen or staphylococcal enterotoxin B and were independent of extracellular type I interferon or IL-10. Our results show that DCs can regulate memory responses and that PDCs rapidly induce regulatory cytokines in effector T cells that can suppress bystander activity.
HIV inhibits CD4+ T-cell proliferation by inducing indoleamine 2,3-dioxygenase in plasmacytoid dendritic cells
Authors: Boasso Adriano , Herbeuval Jean-Philippe , Hardy Andrew W. , Anderson Stephanie A. , Dolan Matthew J. , Fuchs Dietmar , Shearer Gene M.
Published: December 2006

Infection with the human immunodeficiency virus type-1 (HIV) results in acute and progressive numeric loss of CD4+ T-helper cells and functional impairment of T-cell responses. The mechanistic basis of the functional impairment of the surviving cells is not clear. Indoleamine 2,3-dioxygenase (IDO) is an immunosuppressive enzyme that inhibits T-cell proliferation by catabolizing the essential amino acid tryptophan (Trp) into the kynurenine (kyn) pathway. Here, we show that IDO mRNA expression is elevated in peripheral blood mononuclear cells (PBMCs) from HIV+ patients compared with uninfected healthy controls (HCs), and that in vitro inhibition of IDO with the competitive blocker 1-methyl tryptophan (1-mT) results in increased CD4+ T-cell proliferative response in PBMCs from HIV-infected patients. We developed an in vitro model in which exposure of PBMCs from HCs to either infectious or noninfectious, R5- or X4-tropic HIV induced IDO in plasmacytoid dendritic cells (pDCs). HIV-induced IDO was not inhibited by blocking antibodies against interferon type I or type II, which, however, induced IDO in pDCs when added to PBMC cultures. Blockade of gp120/CD4 interactions with anti-CD4 Ab inhibited HIV-mediated IDO induction. Thus, induction of IDO in pDCs by HIV may contribute to the T-cell functional impairment observed in HIV/AIDS by a non–interferon-dependent mechanism.
Reduced-intensity conditioning for myeloma: lower nonrelapse mortality but higher relapse rates compared with myeloablative conditioning
Authors: Crawley Charles , Iacobelli Simona , Björkstrand Bo , Apperley Jane F. , Niederwieser Dietger , Gahrton Gösta ,   for the Chronic Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT)
Published: December 2006

Despite the widespread adoption of reduced-intensity conditioning (RIC) for myeloma, there are few data comparing outcomes with RIC with myeloablative conditioning (MAC). We report the outcomes of patients undergoing allogeneic transplantations for myeloma and reported to the EBMT. A minimum data set was available on 320 RIC and 196 MAC allografts performed between 1998 and 2002. The RIC patients were older (51 vs 45 years) with more progressive disease (28% vs 21%) and more had received a prior transplant (76% vs 11%). In addition, there was a longer time to transplantation and an increased use of peripheral blood and T-cell depletion. For RIC and MAC, respectively, the nonrelapse mortality (NRM) at 2 years was 24% and 37% (P = .002); overall survival, 38.1% and 50.8% (not significant [ns]); and progression-free survival (PFS), 18.9% and 34.5% (P = .001). On multivariate analysis, RIC was associated with a reduction in NRM (HR, 0.5), but this was offset by an increase in relapse risk (HR, 2.0), and the conditioning intensity did not impact on overall survival or retain significance for PFS. These data suggest that there is a continuing need to investigate dose intensity in the conditioning for myeloma allografts.
Blockade of adaptive defensive changes in cholesterol uptake and synthesis in AML by the addition of pravastatin to idarubicin + high-dose Ara-C: a phase 1 study
Authors: Kornblau Steven M. , Banker Deborah E. , Stirewalt Derek , Shen Danny , Lemker Elizabeth , Verstovsek Srdan , Estrov Zeev , Faderl Stefan , Cortes Jorge , Beran Miloslav , Jackson C. Ellen , Chen Wenjing , Estey Elihu , Appelbaum Frederick R.
Published: December 2006

Following exposure to cytotoxic agents, acute myeloid leukemia (AML) blasts elevate cellular cholesterol in a defensive adaptation that increases chemoresistance, but blockade of HMG-CoA reductase with statins restores chemosensitivity in vitro. This phase 1 study evaluated adding pravastatin (PV) (40-1680 mg/day, days 1-8) to idarubicin (Ida) ([12 mg/(M2 · day), days 4-6]) + high-dose cytarabine (Ara-C; HDAC) [1.5 g/(M2 · day) by CI, days 4-7] in 15 newly diagnosed and 22 salvage patients with unfavorable (n = 26) or intermediate (n = 10) prognosis cytogenetics. Compared with historical experience with Ida-HDAC, the duration of neutropenia and throbmbocytopenia and the toxicity profile were unaffected by the addition of PV. During PV loading (day 0-4) serum triglyceride and total and LDL cholesterol levels decreased in nearly all patients. Pharmacokinetic studies demonstrated higher and more sustained serum PV levels with PV doses above 1280 mg/day. CR/CRp was obtained in 11 of 15 new patients, including 8 of 10 with unfavorable cytogenetics, and 9 of 22 salvage patients. An MTD for PV + Ida-HDAC was not reached. Addition of PV to Ida-HDAC was safe, and the encouraging response rates support conducting further trials evaluating the effect of cholesterol modulation on response in AML.
Deep and comparative analysis of the mycelium and appressorium transcriptomes of Magnaporthe grisea using MPSS, RL-SAGE, and oligoarray methods
Authors: Gowda Malali , Venu RC , Raghupathy Mohan B , Nobuta Kan , Li Huameng , Wing Rod , Stahlberg Eric , Couglan Sean , Haudenschild Christian D , Dean Ralph , Nahm Baek-Hie , Meyers Blake C , Wang Guo-Liang
Published: December 2006

Background

Rice blast, caused by the fungal pathogenMagnaporthe grisea, is a devastating disease causing tremendous yield loss in rice production. The public availability of the complete genome sequence ofM. griseaprovides ample opportunities to understand the molecular mechanism of its pathogenesis on rice plants at the transcriptome level. To identify all the expressed genes encoded in the fungal genome, we have analyzed the mycelium and appressorium transcriptomes using massively parallel signature sequencing (MPSS), robust-long serial analysis of gene expression (RL-SAGE) and oligoarray methods.

Results

The MPSS analyses identified 12,531 and 12,927 distinct significant tags from mycelia and appressoria, respectively, while the RL-SAGE analysis identified 16,580 distinct significant tags from the mycelial library. When matching these 12,531 mycelial and 12,927 appressorial significant tags to the annotated CDS, 500 bp upstream and 500 bp downstream of CDS, 6,735 unique genes in mycelia and 7,686 unique genes in appressoria were identified. A total of 7,135 mycelium-specific and 7,531 appressorium-specific significant MPSS tags were identified, which correspond to 2,088 and 1,784 annotated genes, respectively, when matching to the same set of reference sequences. Nearly 85% of the significant MPSS tags from mycelia and appressoria and 65% of the significant tags from the RL-SAGE mycelium library matched to theM. griseagenome. MPSS and RL-SAGE methods supported the expression of more than 9,000 genes, representing over 80% of the predicted genes inM. grisea. About 40% of the MPSS tags and 55% of the RL-SAGE tags represent novel transcripts since they had no matches in the existingM. griseaEST collections. Over 19% of the annotated genes were found to produce both sense and antisense tags in the protein-coding region. The oligoarray analysis identified the expression of 3,793 mycelium-specific and 4,652 appressorium-specific genes. A total of 2,430 mycelial genes and 1,886 appressorial genes were identified by both MPSS and oligoarray.

Conclusion

The comprehensive and deep transcriptome analysis by MPSS and RL-SAGE methods identified many novel sense and antisense transcripts in theM. griseagenome at two important growth stages. The differentially expressed transcripts that were identified, especially those specifically expressed in appressoria, represent a genomic resource useful for gaining a better understanding of the molecular basis ofM. griseapathogenicity. Further analysis of the novel antisense transcripts will provide new insights into the regulation and function of these genes in fungal growth, development and pathogenesis in the host plants.
Intracellular expression of toll-like receptor 4 in neuroblastoma cells and their unresponsiveness to lipopolysaccharide
Authors: Hassan Ferdaus , Islam Shamima , Tumurkhuu Gantsetseg , Naiki Yoshikazu , Koide Naoki , Mori Isamu , Yoshida Tomoaki , Yokochi Takashi
Published: December 2006

Background

Recently it has been reported that, toll-like receptors (TLRs) are expressed on a series of tumor cells, such as colon cancer, breast cancer, prostate cancer, melanoma and lung cancer. Although some cancer cells like melanoma cells are known to respond to lipopolysaccharide (LPS) via TLR4, not all cancer cells are positive for TLR4. There is little information on the expression and function of TLR4 in neuroblastoma cells. In this study, we investigated the expression of TLR4 in human neuroblastoma NB-1 cell line.

Methods

Expression and localization of TLR4 were detected by reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometric analysis, respectively. Activation of nuclear factor (NF)-κB by LPS was detected by degradation of IκB-α and NF-κB luciferase assay. Activation and expression of mitogen-activated protein (MAP) kinase and interferon regulatory factor (IRF)-3 was detected by immunoblot analysis.

Results

Human NB-1 neuroblastoma cells expressed intracellular form of TLR4, but not the cell surface form. Further, NB-1 cells express CD14, MD2 and MyD88, which are required for LPS response. However, LPS did not significantly induce NF-κB activation in NB-1 cells although it slightly degraded IκB-α. NB-1 cells expressed no IRF-3, which plays a pivotal role on the MyD88-independent pathway of LPS signaling. Collectively, NB-1 cells are capable to avoid their response to LPS.

Conclusion

Although human NB-1 neuroblastoma cells possessed all the molecules required for LPS response, they did not respond to LPS. It might be responsible for intracellular expression of TLR4 or lack of IRF-3.
p150 ADAR1 isoform involved in maintenance of HeLa cell proliferation
Authors: Wang Haifang , Hou Zheng , Wu Yumei , Ma Xue , Luo Xiaoxing
Published: December 2006

Background

RNA-specific adenosine deaminase ADAR1 is ubiquitously expressed in a variety of mammalian cells and tissues. Although its physiological importance in non-nervous tissues has been confirmed by analysis of null mutation phenotypes, few endogenous editing substrates have been identified in numerous peripheral tissues and biological function of ADAR1 has not been fully understood.

Methods

A conditional site-specific, ribozyme-based gene knock-down strategy was utilized to study the function of full-length isoform of ADAR1 (p150 protein) in HeLa cell. Double-stable HeLa cell lines were developed by transfecting HeLa Tet-On cells with a pTRE-derived plasmid that can express a hammerhead ribozyme against mRNA of p150 ADAR1 isoform under induction condition. Semi-quantitative RT-PCR and Western blotting were performed to measure the expression of p150 in selected cell clones. Cell proliferation was evaluated by means of MTT assay and growth curve analysis. Cellular morphological changes were observed under light microscope. Flow Cytometry was used for cell cycle analysis. Growth rate of cell transplants in BALB/c nude mice was also investigated.

Results

Both HeLa cell proliferation in vitro and the growth rate of transplanted HeLa cell-derived tumors in nude mice in vivo were significantly inhibited due to reduced expression of ADAR1 p150. Additionally, cell cycle analysis showed that cell progression from G1 phase to S phase was retarded in the ADAR1 p150 suppressed cells.

Conclusion

Our results suggest that normal expression and functioning of p150 ADAR1 is essential for the maintenance of proper cell growth. The mechanisms underlying ADAR1's action might include both editing of currently unknown double-stranded RNAs and interacting with other cellular dsRNA-related processes.
Exosomes released by EBV-infected nasopharyngeal carcinoma cells convey the viral Latent Membrane Protein 1 and the immunomodulatory protein galectin 9
Authors: Keryer-Bibens Cécile , Pioche-Durieu Catherine , Villemant Cécile , Souquère Sylvie , Nishi Nozomu , Hirashima Mitsuomi , Middeldorp Jaap , Busson Pierre
Published: December 2006

Background

Nasopharyngeal carcinomas (NPC) are consistently associated with the Epstein-Barr virus (EBV). Their malignant epithelial cells contain the viral genome and express several antigenic viral proteins. However, the mechanisms of immune escape in NPCs are still poorly understood. EBV-transformed B-cells have been reported to release exosomes carrying the EBV-encoded latent membrane protein 1 (LMP1) which has T-cell inhibitory activity. Although this report suggested that NPC cells could also produce exosomes carrying immunosuppressive proteins, this hypothesis has remained so far untested.

Methods

Malignant epithelial cells derived from NPC xenografts – LMP1-positive (C15) or negative (C17) – were used to prepare conditioned culture medium. Various microparticles and vesicles released in the culture medium were collected and fractionated by differential centrifugation. Exosomes collected in the last centrifugation step were further purified by immunomagnetic capture on beads carrying antibody directed to HLA class II molecules. Purified exosomes were visualized by electron microscopy and analysed by western blotting. The T-cell inhibitory activities of recombinant LMP1 and galectin 9 were assessed on peripheral blood mononuclear cells activated by CD3/CD28 cross-linking.

Results

HLA-class II-positive exosomes purified from C15 and C17 cell supernatants were containing either LMP1 and galectin 9 (C15) or galectin 9 only (C17). Recombinant LMP1 induced a strong inhibition of T-cell proliferation (IC50 = 0.17 nM). In contrast recombinant galectin 9 had a weaker inhibitory effect (IC50 = 46 nM) with no synergy with LMP1.

Conclusion

This study provides the proof of concept that NPC cells can release HLA class-II positive exosomes containing galectin 9 and/or LMP1. It confirms that the LMP1 molecule has intrinsic T-cell inhibitory activity. These findings will encourage investigations of tumor exosomes in the blood of NPC patients and assessment of their effects on various types of target cells.
Development of a pooled probe method for locating small gene families in a physical map of soybean using stress related paralogues and a BAC minimum tile path
Authors: Shopinski Kay L , Iqbal Muhammad J , Shultz Jeffry L , Jayaraman Dheepakkumaran , Lightfoot David A
Published: December 2006

Background

Genome analysis of soybean (Glycine max L.) has been complicated by its paleo-autopolyploid nature and conserved homeologous regions. Landmarks of expressed sequence tags (ESTs) located within a minimum tile path (MTP) of contiguous (contig) bacterial artificial chromosome (BAC) clones or radiation hybrid set can identify stress and defense related gene rich regions in the genome. A physical map of about 2,800 contigs and MTPs of 8,064 BAC clones encompass the soybean genome. That genome is being sequenced by whole genome shotgun methods so that reliable estimates of gene family size and gene locations will provide a useful tool for finishing. The aims here were to develop methods to anchor plant defense- and stress-related gene paralogues on the MTP derived from the soybean physical map, to identify gene rich regions and to correlate those with QTL for disease resistance.

Results

The probes included 143 ESTs from a root library selected by subtractive hybridization from a multiply disease resistant soybean cultivar 'Forrest' 14 days after inoculation with Fusarium solani f. sp. glycines (F. virguliforme). Another 166 probes were chosen from a root EST library (Gm-r1021) prepared from a non-inoculated soybean cultivar 'Williams 82' based on their homology to the known defense and stress related genes. Twelve and thirteen pooled EST probes were hybridized to high-density colony arrays of MTP BAC clones from the cv. 'Forrest' genome. The EST pools located 613 paralogues for 201 of the 309 probes used (range 1–13 per functional probe). One hundred BAC clones contained more than one kind of paralogue. Many more BACs (246) contained a single paralogue of one of the 201 probes detectable gene families. ESTs were anchored on soybean linkage groups A1, B1, C2, E, D1a+Q, G, I, M, H, and O.

Conclusion

Estimates of gene family sizes were more similar to those made by Southern hybridization than by bioinformatics inferences from EST collections. When compared to Arabidopsis thaliana there were more 2 and 4 member paralogue families reflecting the diploidized-tetraploid nature of the soybean genome. However there were fewer families with 5 or more genes and the same number of single genes. Therefore the method can identify evolutionary patterns such as massively extensive selective gene loss or rapid divergence to regenerate the unique genes in some families.
The shunt from the cyclooxygenase to lipoxygenase pathway in human osteoarthritic subchondral osteoblasts is linked with a variable expression of the 5-lipoxygenase-activating protein
Authors: Maxis Kelitha , Delalandre Aline , Martel-Pelletier Johanne , Pelletier Jean-Pierre , Duval Nicolas , Lajeunesse Daniel
Published: December 2006

Osteoarthritis (OA) is characterized by articular cartilage degradation and hypertrophic bone changes with osteophyte formation and abnormal bone remodeling. Two groups of OA patients were identified via the production of variable and opposite levels of prostaglandin E2 (PGE2) or leukotriene B4 (LTB4) by subchondral osteoblasts, PGE2 levels discriminating between low and high subgroups. We studied whether the expression of 5-lipoxygenase (5-LO) or 5-LO-activating protein (FLAP) is responsible for the shunt from prostaglandins to leukotrienes. FLAP mRNA levels varied in low and high OA groups compared with normal, whereas mRNA levels of 5-LO were similar in all osteoblasts. Selective inhibition of cyclooxygenase-2 (COX-2) with NS-398-stimulated FLAP expression in the high OA osteoblasts subgroup, whereas it was without effect in the low OA osteoblasts subgroup. The addition of PGE2 to the low OA osteoblasts subgroup decreased FLAP expression but failed to affect it in the high OA osteoblasts subgroup. LTB4 levels in OA osteoblasts were stimulated about twofold by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) plus transforming growth factor-β (TGF-β), a situation corresponding to their effect on FLAP mRNA levels. Treatments with 1,25(OH)2D3 and TGF-β also modulated PGE2 production. TGF-β stimulated PGE2 production in both OA osteoblast groups, whereas 1,25(OH)2D3 alone had a limited effect but decreased the effect of TGF-β in the low OA osteoblasts subgroup. This modulation of PGE2 production was mirrored by the synthesis of COX-2. IL-18 levels were only slightly increased in a subgroup of OA osteoblasts compared with normal; however, no relationship was observed overall between IL-18 and PGE2 levels in normal and OA osteoblasts. These results suggest that the shunt from the production of PGE2 to LTB4 is through regulation of the expression of FLAP, not 5-LO, in OA osteoblasts. The expression of FLAP in OA osteoblasts is also modulated differently by 1,25(OH)2D3 and TGF-β depending on their endogenous low and high PGE2 levels.
Informed consent for research obtained during the intensive care unit stay
Authors: Chenaud Catherine , Merlani Paolo , Luyasu Samuel , Ricou Bara
Published: December 2006

Introduction

Patients in the intensive care unit (ICU) may be in an inadequate condition to give their informed consent for research. The aim of this study was to analyse the ability to recall participation in a clinical trial for which ICU patients had given their consent.

Methods

The data presented are a two-step observational study: first, a protocolled informed consent procedure was conducted then the informed consent was given by the patient, and second, a patient interview was held 10 ± 2 days later by the same investigator. The primary endpoints were the ability to recall their participation in the clinical trial, as well as its purpose and related risks. As secondary endpoints, we investigated whether asking questions about the clinical trial or reading the informative leaflet was related to the recall. To be included in the study, the patient had to have a Glasgow Coma Scale score of 15, be fully oriented and free of mechanical ventilation, and be judged competent by both the investigator and the attending physician. Patients admitted to the ICU after major surgery or trauma were eligible. However, patients who refused to participate, or those whose next-of-kin gave consent, were excluded.

Results

Of the 44 patients, 35 (80%) recognized, 10 to 12 days after informed consent had been obtained, that they had participated in the clinical trial, but only 14 out of 44 (32%) could recall the clinical trial purpose and its related risks. More patients with complete recall had read the informative leaflet or asked at least one question before signing the informed consent. Asking at least one question was associated with complete recall.

Conclusion

Our results confirm that obtaining informed consent for research during an ICU stay is associated with poor patient recall of participation in a clinical trial and its components (purpose and risk). Whether encouraging reading the informative leaflet and asking questions about the clinical trial improves the informed consent procedure remains to be fully investigated.
Trimodality Treatment and Selective Organ Preservation for Bladder Cancer
Authors: Rödel Claus , Weiss Christian , Sauer Rolf
Published: December 2006

Standard treatment for muscle-invasive bladder cancer is cystectomy. Trimodality treatment, including transurethral resection of the bladder tumor (TURBT), radiation therapy and chemotherapy, has been shown to produce survival rates comparable to those of cystectomy. With these programs, cystectomy has been reserved for patients with incomplete response or local relapse. During the past 15 years, organ preservation by trimodality treatment has been investigated in prospective series from single centers and cooperative groups, with more than 1,000 patients included. Five-year overall survival rates in the range of 50% to 60% have been reported, and approximately three quarters of the surviving patients maintained their bladder. Clinical criteria helpful in determining ideal patients for bladder preservation include early tumor stage (including high-risk T1 disease), a visibly complete TURBT, and absence of ureteral obstruction. Close coordination among all disciplines is required to achieve optimal results. Future investigations will focus on (1) optimizing radiation techniques and incorporating more effective systemic chemotherapy, and (2) the proper selection of patients based on molecular makers.
Systemic Chemotherapy for Advanced Bladder Cancer: Update and Controversies
Authors: Garcia Jorge A. , Dreicer Robert
Published: December 2006

Despite improvements in surgical techniques and outcomes, 5-year survival rates for patients with muscle-invasive bladder cancer remain suboptimal. Almost 50% of patients will eventually progress and develop systemic disease. Although various single agents have shown activity in patients with advanced or metastatic disease, randomized trials have demonstrated the utility of cisplatin-based combinations regimens. Despite relatively high objective response rates, the impact on survival in patients with advanced disease has been quite limited. Surgical resection in selected patients achieving significant objective response to cytotoxic therapy can contribute to long-term survival rates. The role of salvage therapy in advanced disease remains undefined. Evaluation of several active compounds has yielded unimpressive results with low objective response rates and overlapping CIs. Recognition that the maximum benefit from conventional cytotoxics has been achieved has led to the recent initiation of a number of clinical trials evaluating targeted agents in the management of advanced urothelial cancer.
Role of Cytokine Therapy in 2006 and Beyond for Metastatic Renal Cell Cancer
Authors: Parton Marina , Gore Martin , Eisen Tim
Published: December 2006

Metastatic renal cell cancer (mRCC) has a long history as a disease with poor prognosis and limited therapeutic options. Immunotherapy has been the mainstay of treatment since the 1980s, and there have been a number of largely phase II studies examining various schedules of interferon-alpha and interleukin-2 based treatments. With the development of molecular targeted drugs the armentarium against mRCC has significantly expanded and cytokine treatments should be only directed at those most likely to benefit with durable remissions and prolonged survival.
Evolving Principles of Surgical Management and Prognostic Factors for Outcome in Renal Cell Carcinoma
Authors: Lam John S. , Breda Alberto , Belldegrun Arie S. , Figlin Robert A.
Published: December 2006

The generally accepted principles for the surgical management of renal cell carcinoma (RCC) were first described more than 30 years ago. Since then, much has changed in the understanding of the basic biology and genetics of kidney cancer. Improvements in cross-sectional imaging has allowed for more accurate preoperative clinical staging of renal tumors, and the necessity of completing all the components of the radical nephrectomy have been questioned. Surgical techniques have also evolved, and technology has advanced to make possible new methods of managing renal tumors. The TNM staging system is currently the most extensively used system to provide prognostic information for RCC. However, data published in the last few years has led to significant controversies as to whether further revisions are needed and whether improvements can be made with the introduction of new, more accurate and predictive prognostic factors. Furthermore, the recent discovery of molecular tumor markers are expected to revolutionize the staging of RCC and lead to the development of new therapies based on molecular targeting. This review will examine the evolving principles in the surgical management of RCC as well as provide an update on current staging modalities and prognostic factors.
Immunotherapy for Renal Cell Cancer
Authors: Yang James C. , Childs Richard
Published: December 2006

For eligible patients, the value of immunotherapy for metastatic clear-cell renal cancer is its curative potential, as demonstrated by long-term follow-up after interleukin-2. Advances in cellular therapies, manipulation of activating and inhibitory receptors on T cells and modification of allotransplantation regimens have all produced new tumor regressions in patients who did not respond to conventional interleukin-2 regimens. It is clear that renal cancer remains one of the most immunoresponsive of human malignancies and that advances in immune modulation are again translating into clinical responses for patients with this disease. As the array of biologic therapies for renal cancer expands with the approval of tyrosine kinase inhibitors, immunotherapy, the only modality that can cure widespread renal cancer, must not be overlooked.
Biology and Genetics of Adult Male Germ Cell Tumors
Authors: Houldsworth Jane , Korkola James E. , Bosl George J. , Chaganti R. S. K.
Published: December 2006

Adult male germ cell tumors (GCTs) arise by transformation of totipotent germ cells. They have the unique potential to activate molecular pathways, in part mimicking those occurring during gametogenesis and normal human development, as evidenced by the array of histopathologies observed in vivo. Recent expression profiling studies of GCTs along with advances in embryonic stem-cell research have contributed to our understanding of the underlying biology of the disease. Gain of the short arm of chromosome 12 detected in almost all adult GCTs appears to be multifunctional in germ cell tumorigenesis on the basis of the observed overexpression of genes mapped to this region involved in maintenance of pluripotency and oncogenesis. Expression signatures associated with the different histopathologies have yielded clues as to the functional mechanisms involved in GCT invasion, loss of pluripotency, and lineage differentiation. Genomic and epigenomic abnormalities that contribute to or cause these events have been identified by traditional genome analyses and continue to be revealed as genome-scanning technologies develop. Given the high sensitivity of most GCTs to cisplatin-based treatment, these tumors serve as an excellent model system for the identification of factors associated with drug resistance, including differentiation status and acquisition of genomic alterations. Overall, adult male GCTs provide a unique opportunity for the examination of functional links between transformation and pluripotency, genomic and epigenomic abnormalities and lineage differentiation, and the identification of genetic features associated with chemotherapy resistance.
Targeted Therapy for Metastatic Renal Cell Carcinoma
Authors: Motzer Robert J. , Bukowski Ronald M.
Published: December 2006

The discovery of a relationship for the VHL tumor suppressor gene, hypoxia inducible factor-1 alpha, and vascular endothelial growth factor in the growth of clear-cell renal cell carcinoma (RCC) has identified a pathway for novel targeted therapy. This study evaluated the impact of these agents on metastatic RCC (mRCC), and highlights recent phase II and III trials. A systematic review examined the clinical data for novel targeted agents in mRCC, with a focus on randomized phase II and III trials of the novel targeted agents sunitinib, temsirolimus, sorafenib, and bevacizumab. Several agents, including the small-molecule targeted inhibitors sunitinib, temsirolimus, sorafenib, and the monoclonal antibody bevacizumab, have demonstrated antitumor activity in randomized trials. Superior activity was found with sunitinib and temsirolimus versus cytokines in first-line therapy. Improved progression-free survival was reported with sorafenib and bevacizumab given second-line compared with placebo. Targeted therapies show promising activity in this disease, and they have been changing patient management. Sunitinib and sorafenib were recently approved by the US Food and Drug Administration for treatment of mRCC, These drugs are currently included in clinical practice.
Superficial and Muscle-Invasive Bladder Cancer: Principles of Management for Outcomes Assessments
Authors: Parekh Dipen J. , Bochner Bernard H. , Dalbagni Guido
Published: December 2006

Bladder cancer is a heterogeneous disease. Non–muscle-invasive bladder cancer embraces a spectrum of tumors with varying degrees of clinical behavior. Transurethral resection remains the surgical mainstay for the treatment of non–muscle-invasive bladder cancer. In an attempt to decrease the recurrence or progression rate, intravesical chemotherapy or immunotherapy is also used. Radical cystectomy with bilateral pelvic lymph node dissection remains the gold standard for treating muscle-invasive bladder cancer. Over the last decade, the orthotopic neobladder has gained widespread popularity as the preferred mode of urinary diversion in both males and females with similar oncologic and functional outcomes. Well-designed trials with effective chemotherapy have shown a beneficial role for neoadjuvant chemotherapy.