Added Value of Computed Tomography Virtual Intravascular Endoscopy in the Evaluation of Coronary Arteries with Stents or Plaques

Coronary computed tomography angiography (CCTA) is a widely used imaging modality for diagnosing coronary artery disease (CAD) but is limited by a high false positive rate when evaluating coronary arteries with stents and heavy calcifications. Virtual intravascular endoscopy (VIE) images generated from CCTA can be used to qualitatively assess the vascular lumen and might be helpful for overcoming this challenge. In this study, one hundred subjects with coronary stents underwent both CCTA and invasive coronary angiography (ICA). A total of 902 vessel segments were analyzed using CCTA and VIE. The vessel segments were first analyzed on CCTA alone. Then, using VIE, the segments were classified qualitatively as either negative or positive for in-stent restenosis (ISR) or CAD. These results were compared, using ICA as the reference, to determine the added diagnostic value of VIE. Of the 902 analyzed vessel segments, CCTA/VIE had sensitivity, specificity, accuracy, positive predictive value, and negative predictive value (shown in %) of 93.9/90.2, 96.2/98.2, 96.0/97.7, 70.0/83.1, and 99.4/99.0, respectively, in diagnosing ISR or CAD, with significantly improved specificity (p = 0.025), accuracy (p = 0.046), and positive predictive value (p = 0.047). VIE can be a helpful addition to CCTA when evaluating coronary arterie

A Non-coding RNA of Insect HzNV-1 Virus Establishes Latent Viral Infection through MicroRNA

Heliothis zea nudivirus-1 (HzNV-1) is an insect virus previously known as Hz-1 baculovirus. One of its major early genes, hhi1, is responsible for the establishment of productive viral infection; another gene, pag1, which expresses a non-coding RNA, is the only viral transcript detectable during viral latency. Here we showed that this non-coding RNA was further processed into at least two distinct miRNAs, which targeted and degraded hhi1 transcript. This is a result strikingly similar to a recent report that herpes simplex virus produces tightly-regulated latent specific miRNAs to silence its own key early transcripts. Nevertheless, proof for the establishment of viral latency by miRNA is still lacking. We further showed that HzNV-1 latency could be directly induced by pag1-derived miRNAs in cells infected with a pag1-deleted, latency-deficient virus. This result suggests the existence of a novel mechanism, where miRNAs can be functional for the establishment of viral latency

Ligation of lymphocyte function-associated antigen-1 on monocytes decreases very late antigen-4-mediated adhesion through a reactive oxygen species-dependent pathway

Monocyte-endothelial adhesion plays an important role in monocyte trafficking and hence is important for immune responses and pathogenesis of inflammatory diseases including atherosclerosis. The cross-talk between different integrins on monocytes may be crucial for a coordinated regulation of the cellular adhesion during the complex process of transendothelial migration. By using monoclonal antibodies and recombinant intercellular adhesion molecule 1 (ICAM-1) to engage lymphocyte function-associated antigen 1 (LFA-1) on monocytic cells, we found that the cellular adhesion to vascular cell adhesion molecule 1 (VCAM-1) mediated by very late antigen 4 (VLA-4) was suppressed after this treatment and the suppression depended on the presence of reactive oxygen species (ROSs). Inhibition of production of RoSs through the use of inhibitor of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, but not inhibitors of mitochondrial electron transport chain or xanthine oxidase, revealed that this suppression on VLA-4-mediated cellular binding was mediated by Ross produced by phagocyte NADPH oxidase. Activation of phosphoinositol-3 kinase and Akt appears to mediate this NADPH oxidase activation through p47 phox phosphorylation and Rac-1 activation. Our results provide a novel pathway in which Ross play a critical role in integrin cross-talk in monocytes. This signaling pathway may be important for cellular transition from firm arrest to diapedesis during monocyte trafficking. (C) 2004 by The American Society of Hematology

Seasonal variation and spatial distribution of carbonaceous aerosols in Taiwan

To investigate the physico-chemical properties of aerosols in Taiwan, an observation network was initiated in 2003. In this work, the measurements of the mass concentration and carbonaceous composition of PM(10) and PM(2.5) are presented. Analysis on the data collected in the first 5-years, from 2003 to 2007, showed that there was a very strong contrast in the aerosol concentration and composition between the rural and the urban/suburban stations. The five-year means of EC at the respective stations ranged from 0.9 +/- 0.04 to 4.2 +/- 0.1 mu gC m(-3). In rural areas, EC accounted for 2-3% of PM(10) and 3-5% of PM(2.5) mass loadings, comparing to 4-6% of PM(10) and 4-8% of PM(2.5) in the urban areas. It was found that the spatial distribution of EC was consistent with CO and NO(x) across the network stations, suggesting that the levels of EC over Taiwan were dominated by local sources. The measured OC was split into POC and SOC counterparts following the EC tracer method. Five-year means of POC ranged from 1.8 +/- 0.1 to 9.7 +/- 0.2 mu gC m(-3) among the stations. It was estimated that the POM contributed 5-17% of PM(10) and 7-18% of PM(2.5) in Taiwan. On the other hand, the five-year means of SOC ranged from 1.5 +/- 0.1 to 3.8 +/- 0.3 mu gC m(-3). The mass fractions of SOM were estimated to be 9-19% in PM(10) and 14-22% in PM(2.5). The results showed that the SOC did not exhibit significant urban-rural contrast as did the POC and EC. A significant cross-station correlation between SOC and total oxidant was observed, which means the spatial distribution of SOC in Taiwan was dominated by the oxidant mixing ratio. Besides, correlation was also found between SOC and particulate nitrate, implying that the precursors of SOA were mainly from local anthropogenic sources. In addition to the spatial distribution, the carbonaceous aerosols also exhibited distinct seasonality. In northern Taiwan, the concentrations of all the three carbonaceous components (EC, POC, and SOC) reached their respective minima in the fall season. POC and EC increased drastically in winter and peaked in spring, whereas the SOC was characterized by a bimodal pattern with the maximal concentration in winter and a second mode in summertime. In southern Taiwan, minimal levels of POC and EC occurred consistently in summer and the maxima were observed in winter, whereas the SOC peaked in summer and declined in wintertime. The discrepancies in the seasonality of carbonaceous aerosols between northern and southern Taiwan were most likely caused by the seasonal meteorological settings that dominated the dispersion of air pollutants. Moreover, it was inferred that the Asian pollution outbreaks could have shifted the seasonal maxima of air pollutants from winter to spring in the northern Taiwan, and that the increases in biogenic SOA precursors and the enhancement in SOA yield were responsible for the elevated SOC concentrations in summer

Epidemiology of invasive fungal diseases among patients with haematological disorders in the Asia-Pacific: a prospective observational study

AbstractWe conducted a 2-year multicentre prospective observational study to determine the epidemiology of and mortality associated with invasive fungal diseases (IFDs) among patients with haematological disorders in Asia. Eleven institutions from 8 countries/regions participated, with 412 subjects (28.2% possible, 38.3% probable and 33.5% proven IFDs) recruited. The epidemiology of IFDs in participating institutions was similar to Western centres, with Aspergillus spp. (65.9%) or Candida spp. (26.7%) causing the majority of probable and proven IFDs. The overall 30-day mortality was 22.1%. Progressive haematological disorder (odds ratio [OR] 5.192), invasive candidiasis (OR 3.679), and chronic renal disease (OR 6.677) were independently associated with mortality

Acetogenin and Prenylated Flavonoids from Helminthostachys zeylanica with Inhibitory Activity on Superoxide Generation and Elastase Release by Neutrophils

One new acetogenin, 6-hydroxy-8-pentadecyloxocane-2,7-dione (1), and four new prenylated flavonoids, 4 '' a,5 '',6 '',7 '',8 '',8 '' a-hexahydro-5,3',4'-trihydroxy-5 '',5 '',8 '' a-trimethyl-4H-chromeno[2 '',3 '': 7,6] flavone (2), 4 '' a,5 '',6 '',7 '',8 '',8 '' a-hexahydro5,3', 4',-trihydroxy-5 '',5 '',8 '' a-trimethyl-4Hchromeno[2 '', 3 '': 7,8] flavone (3), 2-(3,4-dihydroxyphenyl)6-((2,2-dimethyl-6-methylenecyclohexyl) methyl)-5,7-dihydroxy-chroman-4-one (4), and 2-(3,4-dihydroxy-2-[(2,6,6-trimethylcyclohex-2-enyl) methyl] phenyl)-3,5,7-trihydroxy-4H-chromen-4-one (5), together with six known compounds, were isolated and purified from the rhizomes of Helminthostachys zeylanica by column chromatography and high performance liquid chromatography (HPLC) via bioactivity-guided fractionation isolation. The structures of the new isolates were elucidated by spectroscopic methods. Compounds 1, 3, and 5 showed inhibitory activities on either superoxide anion generation or elastase release by human neutrophils in response to formyl-L-methionyl-L-leucyl-L-phenylalanine/cytochalasin B (FMLP/CB)

Science Development

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68479/2/10.1177_107554708500600404.pd

Time-Dependent Fatigue Crack Propagation Behavior of Two Solid-Solution-Strengthened Ni-Based Superalloys—INCONEL 617 and HAYNES 230

The fatigue crack propagation (FCP) as well as the sustained loading crack growth (SLCG) behavior of two solid-solution-strengthened Ni-based superalloys, INCONEL 617 (Special Metals Corporation Family of Companies) and HAYNES 230 (Haynes International, Inc., Kokomo, IN), were studied at increased temperatures in laboratory air under a constant stress-intensity- factor (K) condition. The crack propagation tests were conducted using a baseline cyclic triangular waveform with a frequency of 1 3 Hz. Various hold times were imposed at the maximum load of a fatigue cycle to study the hold time effect. The results show that a linear elastic fracture mechanics (LEFM) parameter, stress intensity factor (K), is sufficient to describe the FCP and SLCG behavior at the testing temperatures ranging from 873 K to 1073 K (600 C to 800 C). As observed in the precipitation-strengthened superalloys, both INCONEL 617 and HAYNES 230 exhibited the time-dependent FCP, steady SLCG behavior, and existence of a damage zone ahead of crack tip. A thermodynamic equation was adapted to correlate the SLCG rates to determine thermal activation energy. The fracture modes associated with crack propagation behavior were discussed, and the mechanism of time-dependent FCP as well as SLCG was identified. Compared with INCONEL 617, the lower crack propagation rates of HAYNES 230 under the time-dependent condition were ascribed to the different fracture mode and the presence of numerous W-rich M6C-type and Cr-rich M23C6-type carbides. Toward the end, a phenomenological model was employed to correlate the FCP rates at cycle/time-dependent FCP domain. All the results suggest that an environmental factor, the stress assisted grain boundary oxygen embrittlement (SAGBOE) mechanism, is mainly responsible for the accelerated time dependent FCP rates of INCONEL 617 and HAYNES 230

Role of calcineurin in Porphyromonas gingivalis-induced myocardial cell hypertrophy and apoptosis

Background and objective: Periodontal pathogen Porphyromonas gingivalis (P. gingivalis) increased cardiomyocyte hypertrophy and apoptosis whereas Actinobaeillus actinomycetemcomitans and Prevotella intermedia had no effects. The purpose of this study is to clarify the role of calcineurin signaling pathway in P. gingivalis-induced H9c2 myocardial cell hypertrophy and apoptosis. Methods: DNA fragmentation, nuclear condensation, cellular morphology, calcineurin protein, Bcl2- associated death promoter (Bad) and nuclear factor of activated T cell (NFAT)-3 protein products in cultured H9c2 myocardial cell were measured by agarose gel electrophoresis, DAPI, immunofluorescence, and Western blotting following P. gingivalis and/or pre-administration of CsA (calcineurin inhibitors cyclosporin A). Results: P. gingivalis not only increased calcineurin protein, NFAT-3 protein products and cellular hypertrophy, but also increased DNA fragmentation, nuclear condensation and Bad protein products in H9c2 cells. The increased cellular sizes, DNA fragmentation, nuclear condensation, and Bad of H9c2 cells treated with P. gingivalis were all significantly reduced after pre-administration of CsA. Conclusion: Our findings suggest that the activity of calcineurin signal pathway may be initiated by P. gingivalis and further lead to cell hypertrophy and death in culture H9c2 myocardial cells

GNL3L stabilizes the TRF1 complex and promotes mitotic transition

Telomeric repeat binding factor 1 (TRF1) is a component of the multiprotein complex “shelterin,” which organizes the telomere into a high-order structure. TRF1 knockout embryos suffer from severe growth defects without apparent telomere dysfunction, suggesting an obligatory role for TRF1 in cell cycle control. To date, the mechanism regulating the mitotic increase in TRF1 protein expression and its function in mitosis remains unclear. Here, we identify guanine nucleotide-binding protein-like 3 (GNL3L), a GTP-binding protein most similar to nucleostemin, as a novel TRF1-interacting protein in vivo. GNL3L binds TRF1 in the nucleoplasm and is capable of promoting the homodimerization and telomeric association of TRF1, preventing promyelocytic leukemia body recruitment of telomere-bound TRF1, and stabilizing TRF1 protein by inhibiting its ubiquitylation and binding to FBX4, an E3 ubiquitin ligase for TRF1. Most importantly, the TRF1 protein-stabilizing activity of GNL3L mediates the mitotic increase of TRF1 protein and promotes the metaphase-to-anaphase transition. This work reveals novel aspects of TRF1 modulation by GNL3L