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Babita Aneja, Mohammad Irfan, Charu Kapil, Mohamad Aman Jairajpuri, Ronan Maguire, Kevin Kavanagh, M Moshahid A Rizvi, Nikhat Manzoor, Amir Azam, Mohammad Abid
The increasing incidence of human candidiasis and the tendency of Candida species to become resistant to existing chemotherapies are well-recognized health problems. The present study demonstrates the successful synthesis of novel triazole-amino acid hybrids with potent in vitro and in vivo inhibitory activity against Candida species. Particularly, compounds 68 and 70 showed potent in vitro activity against fluconazole (FLC) resistant as well as sensitive clinical isolates of Candida albicans. Time kill curve analysis of lead inhibitors 68 and 70 showed their fungistatic nature...
October 13, 2016: Organic & Biomolecular Chemistry
Carsten Paul Bramlage, Britta Froelich, Manuel Wallbach, Joan Minguet, Clemens Grupp, Cornelia Deutsch, Peter Bramlage, Michael Koziolek, Gerhard Anton Müller
In patients with rheumatic diseases, reliable markers for determining disease activity are scarce. One potential parameter is the level of immunoglobulin free light chains (FLCs), which is known to be elevated in the blood of patients with certain rheumatic diseases. Few studies have quantified FLCs in urine, a convenient source of test sample, in patients with different rheumatic diseases. We carried out a retrospective analysis of patients with rheumatic disease attending the University hospital of Goettingen, Germany...
October 12, 2016: Clinical Rheumatology
Thomas Dejoie, Jill Corre, Helene Caillon, Cyrille Hulin, Aurore Perrot, Denis Caillot, Eileen Boyle, Marie-Lorraine Chretien, Jean Fontan, Karim Belhadj, Sabine Brechignac, Olivier Decaux, Laurent Voillat, Philippe Rodon, Olivier Fitoussi, Carla Araujo, Lotfi Benboubker, Charlotte Fontan, Mourad Tiab, Pascal Godmer, Odile Luycx, Olivier Allangba, Jean-Michel Pignon, Jean-Gabriel Fuzibet, Laurence Legros, Anne-Marie Stoppa, Mamoun Dib, Brigitte Pegourie, Frederique Orsini-Piocelle, Lionel Karlin, Bertrand Arnulf, Murielle Roussel, Laurent Garderet, Mohamad Mohty, Nathalie Meuleman, Chantal Doyen, Pascal Lenain, Margaret Macro, Xavier Leleu, Thierry Facon, Philippe Moreau, Michel Attal, Herve Avet-Loiseau
Guidelines for monitoring multiple myeloma patients expressing light chains only (light chain multiple myeloma; LCMM) rely on measurements of the monoclonal protein in urine. Alternatively serum free light chain (sFLC) measurements have better sensitivity over urine methods, however, demonstration that improved sensitivity provides any clinical benefit is lacking. Here we compared the performance of serum and urine measurements in 113 (72κ, 41λ) newly diagnosed LCMM patients enrolled onto the IFM-2009 trial...
October 11, 2016: Blood
Jing Shao, GaoXiang Shi, TianMing Wang, DaQiang Wu, ChangZhong Wang
Candida tropicalis has emerged as an important pathogenic fungus in nosocomial infections due to its recalcitrant resistance to conventional antifungal agents, especially to fluconazole (FLC). Berberine (BBR) is a bioactive herbal-originated alkaloids and has been reported to possess antifungal functions against C. albicans. In this paper, we tried to figure out the antifungal mechanisms of BBR and/or FLC in a clinical C. tropicalis isolate 2006. In the microdilution test, the minimum inhibitory concentration (MIC) of BBR was found 16 μg/mL with fractional inhibitory concentration index (FICI) 0...
2016: Frontiers in Microbiology
Stefanie Rosa, Susan Duncan, Caroline Dean
Antisense transcription through genic regions is pervasive in most genomes; however, its functional significance is still unclear. We are studying the role of antisense transcripts (COOLAIR) in the cold-induced, epigenetic silencing of Arabidopsis FLOWERING LOCUS C (FLC), a regulator of the transition to reproduction. Here we use single-molecule RNA FISH to address the mechanistic relationship of FLC and COOLAIR transcription at the cellular level. We demonstrate that while sense and antisense transcripts can co-occur in the same cell they are mutually exclusive at individual loci...
October 7, 2016: Nature Communications
Alfredo Gagliardi, Claudio Carbone, Angela Russo, Rosanna Cuccurullo, Anna Lucania, Paola Della Cioppa, Gabriella Misso, Michele Caraglia, Catello Tommasino, Lucia Mastrullo
Monoclonal gammopathies are characterized by serum monoclonal component (MC) plus an intact immunoglobulin and a free light chain (FLC), or a combination of both. The measurement of FLC with Freelite(®) is the standard practice recommended by International Myeloma Working Group guidelines. Recently, Hevylite(®) heavy/light chains (HLC) assays were introduced to specifically target junctional epitopes between the heavy and light chains of intact immunoglobulins, allowing the independent quantification of the involved (MC) and uninvolved (polyclonal immunoglobulin background) HLC isotype...
October 2016: Oncology Letters
Pamela Thomson, Emilio Mayayo, Loida López-Fernández, Josep Guarro, Javier Capilla
Cryptococcus albidus and Cryptococcus laurentii are uncommon species of this genus that in recent decades have increasingly caused opportunistic infections in humans, mainly in immunocompromised patients; the best therapy for such infection being unknown. Using a murine model of systemic infection by these fungi, we have evaluated the efficacy of amphotericin B (AMB) at 0.8 mg/kg, administered intravenously, fluconazole (FLC) or voriconazole (VRC), both administered orally, at 25 mg/kg and the combination of AMB plus VRC against three C...
October 3, 2016: Mycoses
H J Park, W-Y Kim, J M Pardo, D-J Yun
Plants have adapted to environmental changes and stresses over generations. The decision of transition from the vegetative to reproductive stage is critical, particularly under unfavorable conditions. Thus, plants appear to have developed mechanisms by which environmental factors or inputs are transmitted to stress response signaling pathways to confer tolerance and are simultaneously integrated into flowering regulation pathways (photoperiod, vernalization, autonomous, and gibberellic acid signaling) to propagate the next generation...
2016: International Review of Cell and Molecular Biology
Kanji Miyazaki, Kenshi Suzuki
Capillary electrophoresis/immunosubtraction (CE/IS) is a simple method for detecting and immunotyping serum or urine monoclonal proteins. To our knowledge, there are no previous reports of the use of CE/IS for characterizing patients with Immunoglobulin light chain (AL) amyloidosis, and there are no convincing data available to compare CE/IS with serum immunofixation electrophoresis (IFE) and free light chain (FLC) assay. The aim of this study was to evaluate the clinical utility of CE/IS in patients with AL amyloidosis as a diagnostic accuracy study...
September 28, 2016: Amyloid: the International Journal of Experimental and Clinical Investigation
Phillipa White, Dimitra Sakellari, Helen Roberts, Idyli Risafi, Martin Ling, Paul Cooper, Mike Milward, Iain Chapple
AIMS: To investigate ex vivo peripheral neutrophil extracellular trap (NET) production and their subsequent degradation by plasma in chronic periodontitis patients, and periodontally and systemically healthy-matched controls. MATERIALS AND METHODS: Chronic periodontitis patient and control (n=40 pairs) peripheral blood neutrophils were stimulated for NET quantification. A subset of patients received non-surgical periodontal therapy (n=19) and NETs were quantified 3-months later alongside controls...
September 28, 2016: Journal of Clinical Periodontology
Tatiana Prokaeva, Brian Spencer, Fangui Sun, Richard M O'Hara, David C Seldin, Lawreen H Connors, Vaishali Sanchorawala
BACKGROUND: Serum and urine immunofixation electrophoreses (SIFE/UIFE) are used for clonal detection in plasma cell dyscrasias, while serum free light chain (sFLC) testing provides quantitation of clonal disease. Up to 20% of patients with light chain (AL) amyloidosis may present with normal FLC ratio (FLCr). METHODS: We assessed the diagnostic, quantitative and prognostic potential of serum heavy light chain ratio (HLCr) in 199 untreated patients at initial evaluation...
September 28, 2016: Amyloid: the International Journal of Experimental and Clinical Investigation
Irit Avivi, Yael C Cohen, Erel Joffe, Noam Benyamini, Viki Held-Kuznetsov, Svetlana Trestman, Evangelos Terpos, Meletios A Dimopoulos, Efstathios Kastritis
Multiple myeloma (MM) is a multi-subclonal malignancy with relatively high heterogeneity. Patients who initially presented with both monoclonal-protein (MP) and free light chain (FLC) secretion but then relapsed with a light chain escape pattern have been shown to reflect disease clonal evolution and to bare a worse prognosis. We hypothesized that a discordant MP/FLC pattern at diagnosis may reflect a similar clonal evolution that had occurred prior to diagnosis of active myeloma, conferring a worse outcome...
September 19, 2016: Hematological Oncology
Sergio Barros-Gomes, Brittney Williams, Lara F Nhola, Martha Grogan, Joseph F Maalouf, Angela Dispenzieri, Patricia A Pellikka, Hector R Villarraga
OBJECTIVES: This study evaluated whether 2-dimensional speckle-tracking echocardiography (2D-STE) has incremental value for prognosis over traditional clinical, echocardiographic, and serological markers-with main focus on the current prognostic staging system-in light-chain (AL) amyloidosis patients with preserved left ventricular ejection fraction. BACKGROUND: Cardiac amyloidosis (CA) is the major determinant of outcome in AL amyloidosis. The current prognostic staging system is based primarily on serum levels of cardiac troponin T (cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and free light chain differential (FLC-diff)...
September 8, 2016: JACC. Cardiovascular Imaging
Wenli Feng, Jing Yang, Yiru Wang, Jinyu Chen, Zhiqin Xi, Zusha Qiao
To better understand the association between the ERG11 gene and drug resistance in Candida krusei, C. krusei strains were isolated from patients from January 2010 to May 2013. Susceptibility to 5-fluorocytosine (5-FC), amphotericin B (AMB), voriconazole (VRC), fluconazole (FLC), and itraconazole (ITR) were tested by broth microdilution method. Mutations were detected using PCR amplification and gene sequencing. Expression levels of ERG11 were measured by real-time PCR and compared by a 2-tailed Student's t test between ITR-susceptible strains and ITR-resistant strains...
July 14, 2016: Canadian Journal of Microbiology
Caroline Moreau, Brice Autier, Thibault Cavey, Emmanuel Rouger, James Norwood, Claude Bendavid, Martine Escoffre, Martine Sébillot, Olivier Decaux
BACKGROUND: Free light chain (FLC) assays are essential for diagnosis and follow-up of plasma cell dyscrasia. Two assays are available: Freelite (Binding Site) and N Latex FLC (Siemens). The aim of our study was to evaluate the impact of renal failure on concordance and correlation between the 2 FLC assays. METHODS: FLC measurements using both assays were performed on 1215 fresh serum samples from patients with or without monoclonal gammopathy and renal failure...
August 10, 2016: Clinical Lymphoma, Myeloma & Leukemia
Peiqiang Feng, Hailong Guo, Wei Chi, Xin Chai, Xuwu Sun, Xiumei Xu, Jinfang Ma, Jean-David Rochaix, Dario Leister, Haiyang Wang, Congming Lu, Lixin Zhang
Light is a major environmental factor regulating flowering time, thus ensuring reproductive success of higher plants. In contrast to our detailed understanding of light quality and photoperiod mechanisms involved, the molecular basis underlying high light-promoted flowering remains elusive. Here we show that, in Arabidopsis, a chloroplast-derived signal is critical for high light-regulated flowering mediated by the FLOWERING LOCUS C (FLC). We also demonstrate that PTM, a PHD transcription factor involved in chloroplast retrograde signaling, perceives such a signal and mediates transcriptional repression of FLC through recruitment of FVE, a component of the histone deacetylase complex...
September 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
Alexander H Kirsch, Raphael Lyko, Lars-Göran Nilsson, Werner Beck, Michael Amdahl, Petra Lechner, Andreas Schneider, Christoph Wanner, Alexander R Rosenkranz, Detlef H Krieter
BACKGROUND: Compared to high-flux dialysis membranes, novel medium cut-off (MCO) membranes show greater permeability for larger middle molecules. METHODS: In two prospective, open-label, controlled, randomized, crossover pilot studies, 39 prevalent hemodialysis (HD) patients were studied in four dialysis treatments as follows: study 1, three MCO prototype dialyzers (AA, BB and CC with increasing permeability) and one high-flux dialyzer in HD; and study 2, two MCO prototype dialyzers (AA and BB) in HD and high-flux dialyzers in HD and hemodiafiltration (HDF)...
September 1, 2016: Nephrology, Dialysis, Transplantation
Yan-Hui Zhou, Ming Zhang, Rong-Xiu Zhu, Jiao-Zhen Zhang, Fei Xie, Xiao-Bin Li, Wen-Qiang Chang, Xiao-Ning Wang, Zun-Tian Zhao, Hong-Xiang Lou
Twelve new heptaketides, biatriosporins A-L (1-12), biatriosporin M (13) (a ramulosin derivative), and 19 known compounds (14-32) were isolated from the endolichenic fungus Biatriospora sp. (8331C). The structures of these compounds were determined by analyzing MS and NMR data. The absolute configurations of compounds 1, 2, 7, and 9 were determined by single-crystal X-ray diffraction analysis, whereas compound 10 was deduced with Mosher's method. Four of the compounds were active in an antifungal assay. The most potent compound, compound 4, also sensitized clinically derived azole-resistant Candida albicans strains to fluconazole (FLC)...
September 23, 2016: Journal of Natural Products
Punit Yadav, Mark Cook, Paul Cockwell
BACKGROUND: Renal impairment (RI) is a common complication of multiple myeloma (MM). Around 50% of patients with MM have RI at presentation, and up to 5% require dialysis treatment. Severe acute kidney injury (AKI) as a cause of RI is a particular challenge as historically the survival of patients who sustain this complication and require dialysis is very poor. However, in this current period, survival is improving and the focus is on optimum use of novel chemotherapies and the evaluation of extra-corporeal therapies for removal of serum immunoglobulin light chains...
March 2016: Kidney Diseases
Mindy C Kohlhagen, David R Barnidge, John R Mills, Joshua Stoner, Kari M Gurtner, Andrea M Liptac, Denise I Lofgren, Patrick M Vanderboom, Angela Dispenzieri, Jerry A Katzmann, Maria A V Willrich, Melissa R Snyder, David L Murray
BACKGROUND: Current recommendations for screening for monoclonal gammopathies include serum protein electrophoresis (PEL), imunofixation electrophoresis (IFE), and free light chain (FLC) ratios to identify or rule out an M-protein. The aim of this study was to examine the feasibility of an assay based on immunoenrichment and MALDI-TOF-MS (MASS-SCREEN) to qualitatively screen for M-proteins. METHODS: Serum from 556 patients previously screened for M-proteins by PEL and IFE were immunopurified using a κ/λ-specific nanobody bead mixture...
October 2016: Clinical Chemistry
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