Myeloid sarcomas: a histologic, immunohistochemical, and cytogenetic study

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Evaluation of lung flute in sputum samples for molecular analysis of lung cancer

BACKGROUND: Molecular analysis of sputum provides a promising approach for lung cancer diagnosis, yet is limited by the difficulty in collecting the specimens from individuals who can’t spontaneously expectorate sputum. Lung Flute is a small self-powered audio device that can induce sputum by generating sound waves and vibrating in the airways of the lungs. Here we propose to evaluate the usefulness of Lung Flute for sputum sampling to assist diagnosis of lung cancer. METHODS: Forty-three stage I lung cancer patients and 47 cancer-free individuals who couldn’t spontaneously cough sputum were instructed to use Lung Flute for sputum sampling. Expressions of two microRNAs, miRs-31 and 210, were determined in the specimens by qRT-PCR. The results were compared with sputum cytology. RESULTS: Sputum was easily collected from 39 of 43 (90.7%) lung cancer patients and 42 of 47 (89.4%) controls with volume ranges from 1 to 5 ml (median, 2.6 ml). The specimens had less than 4% oral squamous cells, indicating that sputum was obtained from low respiratory tract. Expressions of miRs-31 and 210 in sputum were considerably higher in cancer patients than cancer-free individuals (8.990 vs. 4.514; 0.6847 vs. 0.3317; all P <0.001). Combined use of the two miRNAs produced a significantly higher sensitivity (61.5% vs. 35.9%, P = 0.002) and a slightly lower specificity (90.5% vs. 95.2%, p = 0.03) compared with cytology for lung cancer diagnosis. CONCLUSION: Lung Flute could potentially be useful in convenient and efficient collection of sputum for molecular diagnosis of lung cancer

Synthesis of nitroxyl radical by direct nucleophilic functionalization of a C-H bond in the azadiene systems

Cyclic dinitrones underwent nucleophilic substitution of the hydrogen atom in the reaction with a paramagnetic carbanion, the lithium derivative of 4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-1-oxyl 3-oxide, to give polyfunctional nitronyl nitroxyls. © 2012 Springer Science+Business Media New York

A comparative study of optical properties and X-ray induced luminescence of octahedral molybdenum and tungsten cluster complexes

© 2017 The Royal Society of Chemistry. Octahedral metal cluster complexes have high potential for biomedical applications. In order to evaluate the benefits of these moieties for combined CT/X-ray luminescence computed tomography, this paper compares photoluminescence, radiodensity and X-ray induced luminescence properties of eight related octahedral molybdenum and tungsten cluster complexes [{M 6 I 8 }L 6 ] n (where M is Mo or W and L is I - , NO 3 - , OTs - or OH - /H 2 O). This article demonstrates that despite the fact that molybdenum cluster complexes are better photoluminescence emitters, tungsten cluster complexes, in particular (Bu 4 N) 2 [{W 6 I 8 }I 6 ], demonstrate significantly higher X-ray induced luminescence due to a combination of relatively good photoluminescence properties and high X-ray attenuation. Additionally, photo-degradation of [{M 6 I 8 }(NO 3 ) 6 ] 2- was evaluated

Circulating miR-181 is a prognostic biomarker for amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a relentless neurodegenerative disease of the human motor neuron system, where variability in progression rate limits clinical trial efficacy. Therefore, better prognostication will facilitate therapeutic progress. In this study, we investigated the potential of plasma cell-free microRNAs (miRNAs) as ALS prognostication biomarkers in 252 patients with detailed clinical phenotyping. First, we identified, in a longitudinal cohort, miRNAs whose plasma levels remain stable over the course of disease. Next, we showed that high levels of miR-181, a miRNA enriched in neurons, predicts a greater than two-fold risk of death in independent discovery and replication cohorts (126 and 122 patients, respectively). miR-181 performance is similar to neurofilament light chain (NfL), and when combined together, miR-181 + NfL establish a novel RNA–protein biomarker pair with superior prognostication capacity. Therefore, plasma miR-181 alone and a novel miRNA–protein biomarker approach, based on miR-181 + NfL, boost precision of patient stratification. miR-181-based ALS biomarkers encourage additional validation and might enhance the power of clinical trials

Extracellular microRNAs exhibit sequence-dependent stability and cellular release kinetics

Multiple studies have described extracellular microRNAs (ex-miRNAs) as being remarkably stable despite the hostile extracellular environment, when stored at 4oC or lower. Here we show that many ex-miRNAs are rapidly degraded when incubated at 37oC in the presence of serum (thereby simulating physiologically relevant conditions). Stability varied widely between miRNAs, with half-lives ranging from similar to 1.5 hours to more than 13 hours. Notably, ex-miRNA half-lives calculated in two different biofluids (murine serum and C2C12 mouse myotube conditioned medium) were highly similar, suggesting that intrinsic sequence properties are a determining factor in miRNA stability. By contrast, ex-miRNAs associated with extracellular vesicles (isolated by size exclusion chromatography) were highly stable. The release of ex-miRNAs from C2C12 myotubes was measured over time, and mathematical modelling revealed miRNA-specific release kinetics. While some ex-miRNAs reached the steady state in cell culture medium within 24 hours, the extracellular level of miR-16 did not reach equilibrium, even after 3 days in culture. These findings are indicative of miRNA-specific release and degradation kinetics with implications for the utility of ex-miRNAs as biomarkers, and for the potential of ex-miRNAs to transfer gene regulatory information between cells

New approach to synthesis of nitronyl and imino nitroxides based on SNH methodology

It is shown that SN H approach opens new possibilities in the synthesis of polyfunctional nitronyl and imino nitroxides. It is found that the interaction of 4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-3-oxide-1- oxyl lithium salt Li1 with 3,6-diaryl-1,2,4-triazines leads to formation of the corresponding triazines bearing nitronyl nitroxide or imino nitroxide substituent at position 5 of the heterocycle. The reaction of Li1 with pyridazine-N-oxide gives rise to nitroxide with buten-3-ynyl substituent 5. Spin-labeled 5 could be readily transformed by the use of 1,3-dipolar and nucleophilic addition reactions, as well as oxidative coupling, that gives a large group of new paramagnets: 2-(1H-pyrazol-5-yl)vinyl-, 2-ethynylcyclopropyl- , 2-(3-(ethoxycarbonyl) isoxazol-5-yl)vinyl-, 1-(pyrrolidin-1-yl)but-3-ynyl- substituted nitronyl nitroxide and a diradical - 2,2′-((1E,7E)-octa-1,7- dien-3,5-diyne-1,8-diyl)bis(4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-3-oxide- 1-oxyl). The new nitroxides were characterized by X-ray single crystal data, ESR and static magnetic susceptibility measurements. © ARKAT USA, Inc

Structural Basis for a Neutralizing Antibody Response Elicited by a Recombinant Hantaan Virus Gn Immunogen

Hantaviruses are a group of emerging pathogens capable of causing severe disease upon zoonotic transmission to humans. The mature hantavirus surface presents higher-order tetrameric assemblies of two glycoproteins, Gn and Gc, which are responsible for negotiating host cell entry and constitute key therapeutic targets. Here, we demonstrate that recombinantly derived Gn from Hantaan virus (HTNV) elicits a neutralizing antibody response (serum dilution that inhibits 50% infection [ID50], 1:200 to 1:850) in an animal model. Using antigen-specific B cell sorting, we isolated monoclonal antibodies (mAbs) exhibiting neutralizing and non-neutralizing activity, termed mAb HTN-Gn1 and mAb nn-ITN-Gn2, respectively. Crystallographic analysis reveals that these mAbs target spatially distinct epitopes at disparate sites of the N-terminal region of the HTNV Gn ectodomain. Epitope mapping onto a model of the higher order (Gn-Gc)(4) spike supports the immune accessibility of the mAb HTN-Gn1 epitope, a hypothesis confirmed by electron cryo-tomography of the antibody with virus-like particles. These data define natively exposed regions of the hantaviral Gn that can be targeted in immunogen design. IMPORTANCE The spillover of pathogenic hantaviruses from rodent reservoirs into the human population poses a continued threat to human health. Here, we show that a recombinant form of the Hantaan virus (HTNV) surface-displayed glycoprotein, Gn, elicits a neutralizing antibody response in rabbits. We isolated a neutralizing (HTN-Gn1) and a non-neutralizing (nn-ITN-Gn2) monoclonal antibody and provide the first molecular-level insights into how the Gn glycoprotein may be targeted by the antibody-mediated immune response. These findings may guide rational vaccine design approaches focused on targeting the hantavirus glycoprotein envelope.Peer reviewe