作者: Saada, Véronique ; Fernandez-Zapico, Martin E ; Michea, Paula ; Soumelis, Vassili ; Ribrag, Vincent ; Solary, Eric ; Patnaik, Mrinal M ; Duchmann, Matthieu ; Niyongere, Sandrine ; Droin, Nathalie ; Fontenay, Michaela ; Pierron, Gérard ; Rameau, Philippe ; Diop, M'boyba Khadija ; Noël, Floriane ; King, Rebecca L ; Itzykson, Raphael ; Fenaux, Pierre ; Lucas, Nolwenn ; Willekens, Christophe ; Howard, Matthew T ; Padron, Eric ; Kosmider, Olivier

Islands of CD123^high cells have been commonly described in the bone marrow of patients with chronic myelomonocytic leukemia (CMML). Using a multiparameter flow cytometry assay, we detected an excess of CD123⁺ mononucleated cells that are lineage-negative, CD45⁺, CD11c^-, CD33^-, HLA-DR⁺, BDCA-2⁺, BDCA-4⁺ in the bone marrow of 32/159 (20%) patients. Conventional and electron microscopy, flow cytometry detection of cell surface markers, gene expression analyses, and the ability to synthesize interferon alpha in response to Toll-like receptor agonists identified these cells as bona fide plasmacytoid dendritic cells (pDCs). Whole-exome sequencing of sorted monocytes and pDCs identified somatic mutations in genes of the oncogenic RAS pathway in the two cell types of every patient. CD34⁺ cells could generate high amount of pDCs in the absence of FMS-like tyrosine kinase 3-ligand (FLT3L). Finally, an excess of pDCs correlates with regulatory T cell accumulation and an increased risk of acute leukemia transformation. These results demonstrate the FLT3L-independent accumulation of clonal pDCs in the bone marrow of CMML patients with mutations affecting the RAS pathway, which is associated with a higher risk of disease progression.

2010-05-10·Biomacromolecules2区 · 化学

Readily Controllable Step-Growth Polymerization Method for Poly(lactic acid) Copolymers Having a High Glass Transition Temperature

2区 · 化学

Article

作者: Södergård, Anders ; Stolt, Mikael ; Inkinen, Saara

Poly(lactic acid) (PLA) copolymers having a significantly higher glass transition temperature (T(g)) than that of high molar mass PLA homopolymers (typically 60 +/- 5 degrees C) were prepared. Lactic acid was copolymerized with 1,4:3,6-dianhydro-D-glucitol (isosorbide, ISB) and succinic acid (SA-2), 1,2,3,4-butanetetracarboxylic acid (BTCA-4) or 1,2,3,4,5,6-cyclohexanehexacarboxylic acid (HCA-6). The highest T(g)s obtained for the copolymers containing BTCA-4 and HCA-6 were 80 and 86 degrees C, respectively. The polymers were prepared by step-growth polymerization in the melt phase, which is an easily operable and simple PLA production method in comparison to the ring-opening polymerization (ROP) route. It was shown that the T(g) and the cross-linking induced by the polyfunctional carboxylic acid comonomers could be readily controlled by choosing a suitable polymerization time and temperature. Similar improvement in the T(g) as achieved for the copolymers of BTCA-4 and HCA-6 was not observed for linear copolymers containing ISB and SA-2.

2004-12-01·Journal of Natural Products2区 · 生物学

New 3-Oxo-chol-4-en-24-oic Acids from the Marine Soft Coral Eleutherobia sp.

2区 · 生物学

Article

作者: Hope, Håkon ; Molinski, Tadeusz F. ; Lievens, Sarah C.

Two novel cholic acid derivatives and three known steroids were isolated from an octocoral Eleutherobiasp. from Pohnpei Micronesia along with the known briareins minabein-1 (6), minabein-4 (7), minabein-6 (8), minabein-8 (9), and minabein-9 (10). X-ray crystallographic analysis of the known compound minabein-4 allowed assignment of its correct relative and absolute stereochemistry. Consequently, a different structure proposed for the same compound (named independently as nui-inoalide-D) is incorrect.

100 项与 miniABCA-4 相关的药物交易

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