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[PMID]: 29523024
[Au] Autor:Abdollahpour-Alitappeh M; Hashemi Karouei SM; Lotfinia M; Amanzadeh A; Habibi-Anbouhi M
[Ad] Address:a Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases , Shahid Beheshti University of Medical Sciences , Tehran , Iran.
[Ti] Title:A developed antibody-drug conjugate rituximab-vcMMAE shows a potent cytotoxic activity against CD20-positive cell line.
[So] Source:Artif Cells Nanomed Biotechnol;:1-8, 2018 Mar 09.
[Is] ISSN:2169-141X
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Rituximab is a chimeric monoclonal antibody directed against B-lymphocyte specific antigen CD20, which is used for the treatment of B-cell malignancies. However, the effectiveness of rituximab is limited partly due to treatment resistance. The aim of this study was to develop rituximab-based antibody drug conjugate (ADC) to enhance rituximab activity. In this study, monomethyl auristatin E (MMAE) was covalently conjugated to dithiothreitol -reduced rituximab via a valine-citrulline peptide linker (rituximab-vcMMAE). The conjugates were then characterized by using nonreducing sodium dodecyl sulfate-polyacrylamide electrophoresis (SDS-PAGE) and cell-based enzyme-linked immunosorbent assay (ELISA). The cytotoxic activity of the ADC was evaluated against Raji (human B-cell lymphoma; CD20-positive) and MOLT-4 (T lymphoblast; acute lymphoblastic leukemia; CD20-negative) cell lines. In addition, the colony formation assay was used to identify the propagation ability of ADC-treated cells in vitro. Results from nonreducing SDS-PAGE revealed various species of rituximab-MC-Val-Cit-PABC-MMAE (rituximab-vcMMAE), as compared with unconjugated rituximab. The binding capacity of rituximab-vcMMAE to the CD20-positive cell was similar to that of the parental rituximab. Most importantly, our results revealed that rituximab-vcMMAE was highly potent against the CD20-positive cell line, but not against the CD20-negative cell. At the same time, rituximab-vcMMAE was able to inhibit colony formation in CD20-positive cells. These data indicate that rituximab-vcMMAE may be a highly effective and selective therapy for the treatment of B-cell lymphoma.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher
[do] DOI:10.1080/21691401.2018.1449119

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[PMID]: 29486248
[Au] Autor:Zhao M; Li P; Xie Y; Liu X; Cheng L; Liu T; Kong L; Wang O; Han F
[Ad] Address:Key Laboratory for Genetic Hearing Disorders in Shandong, Binzhou Medical University, 346 Guanhai Road, Yantai, Shandong, 264003, PR China; Department of Biochemistry and Molecular Biology, Binzhou Medical University, 346 Guanhai Road, Yantai, Shandong, 264003, PR China.
[Ti] Title:Recombinant protein of the first two ectodomains of cadherin 23 from erl mice shows impairment in Ca -dependent proteolysis protection.
[So] Source:Protein Expr Purif;147:55-60, 2018 Feb 24.
[Is] ISSN:1096-0279
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The erl mouse is a mouse model of nonsyndromic autosomal recessive deafness (DFNB12) on the C57BL/6J background. This project was carried out to express the first two ectodomains of cadherin 23 (CDH23 EC1+2) of erl mice in Escherichia coli and identify the Ca -binding ability of the recombinant protein. DNA sequences of CDH23 EC1+2 from wild type and erl mice were synthesized and cloned into pBV220 plasmids. Recombinant plasmids were transformed into Escherichia coli and expression of CDH23 EC1+2 was induced by increasing the temperature from 30 °C to 42 °C. The proteins were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and antigenicity of proteins was identified by Western Blotting. Inclusion bodies were denatured in 8 M urea, purified by ion-exchange and gel filtration chromatography and refolded with dialysis in buffer containing 0.1% sarkosyl. The Ca -binding ability of CDH23 EC1+2 was determined by Ca -dependent proteolysis protection. The results showed that the sizes and sequences of inserts in recombinant plasmids were consistent with expectation and that the recombinant proteins were found mainly in the form of inclusion bodies which maintain antigenicity. After refolding, the secondary structures of recombinant proteins were measured by circular dichroism (CD) spectra. Moreover, CDH23 EC1+2 from the erl mice showed less Ca -dependent proteolysis protection comparing with that of the wild type control. We therefore concluded that impairment of Ca -dependent protein interaction was likely involved in the progressive hearing loss in erl mice. The results may aid in understanding the mechanism of hearing loss in DFNB12.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:Publisher

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[PMID]: 29521586
[Au] Autor:Tian YS; Zhong D; Liu QQ; Zhao XL; Sun HX; Jin J; Wang HN; Li GZ
[Ad] Address:Department of Neurology, The First Affiliated Hospital, Harbin Medical University, Harbin, Heilong Jiang Province, China.
[Ti] Title:Upregulation of miR-216a exerts neuroprotective effects against ischemic injury through negatively regulating JAK2/STAT3-involved apoptosis and inflammatory pathways.
[So] Source:J Neurosurg;:1-12, 2018 Mar 09.
[Is] ISSN:1933-0693
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:OBJECTIVE Ischemic stroke remains a significant cause of death and disability in industrialized nations. Janus tyrosine kinase (JAK) and signal transducer and activator of transcription (STAT) of the JAK2/STAT3 pathway play important roles in the downstream signal pathway regulation of ischemic stroke-related inflammatory neuronal damage. Recently, microRNAs (miRNAs) have emerged as major regulators in cerebral ischemic injury; therefore, the authors aimed to investigate the underlying molecular mechanism between miRNAs and ischemic stroke, which may provide potential therapeutic targets for ischemic stroke. METHODS The JAK2- and JAK3-related miRNA (miR-135, miR-216a, and miR-433) expression levels were detected by real-time quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blot analysis in both oxygen-glucose deprivation (OGD)-treated primary cultured neuronal cells and mouse brain with middle cerebral artery occlusion (MCAO)-induced ischemic stroke. The miR-135, miR-216a, and miR-433 were determined by bioinformatics analysis that may target JAK2, and miR-216a was further confirmed by 3' untranslated region (3'UTR) dual-luciferase assay. The study further detected cell apoptosis, the level of lactate dehydrogenase, and inflammatory mediators (inducible nitric oxide synthase [iNOS], matrix metalloproteinase-9 [MMP-9], tumor necrosis factor-α [TNF-α], and interleukin-1ß [IL-1ß]) after cells were transfected with miR-NC (miRNA negative control) or miR-216a mimics and subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) damage with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, annexin V-FITC/PI, Western blots, and enzyme-linked immunosorbent assay detection. Furthermore, neurological deficit detection and neurological behavior grading were performed to determine the infarction area and neurological deficits. RESULTS JAK2 showed its highest level while miR-216a showed its lowest level at day 1 after ischemic reperfusion. However, miR-135 and miR-433 had no obvious change during the process. The luciferase assay data further confirmed that miR-216a can directly target the 3'UTR of JAK2, and overexpression of miR-216a repressed JAK2 protein levels in OGD/R-treated neuronal cells as well as in the MCAO model ischemic region. In addition, overexpression of miR-216a mitigated cell apoptosis both in vitro and in vivo, which was consistent with the effect of knockdown of JAK2. Furthermore, the study found that miR-216a obviously inhibited the inflammatory mediators after OGD/R, including inflammatory enzymes (iNOS and MMP-9) and cytokines (TNF-α and IL-1ß). Upregulating miR-216a levels reduced ischemic infarction and improved neurological deficit. CONCLUSIONS These findings suggest that upregulation of miR-216a, which targets JAK2, could induce neuroprotection against ischemic injury in vitro and in vivo, which provides a potential therapeutic target for ischemic stroke.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:Publisher
[do] DOI:10.3171/2017.5.JNS163165

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[PMID]: 29520600
[Au] Autor:Zhang X; Gao T; Peng Q; Song L; Zhang J; Chai Y; Sun D; Song F
[Ad] Address:College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, 163319, China.
[Ti] Title:A strong promoter of a non-cry gene directs expression of the cry1Ac gene in Bacillus thuringiensis.
[So] Source:Appl Microbiol Biotechnol;, 2018 Mar 08.
[Is] ISSN:1432-0614
[Cp] Country of publication:Germany
[La] Language:eng
[Ab] Abstract:Bacillus thuringiensis bacteria show insecticidal activities that rely upon the production of insecticidal crystal proteins, which are encoded by cry or cyt genes and can target a variety of insect pests. It has been shown that cry1Ac is the only cry gene in B. thuringiensis subsp. kurstaki HD73 (B. thuringiensis HD73) and its expression is controlled by both σ and σ . Here, we report a novel σ -dependent strong promoter of a non-cry gene (HD73_5014), which can direct strong cry1Ac gene expression in B. thuringiensis HD73. We constructed an E. coli-B. thuringiensis shuttle vector (pHT315-P -1Ac) for cry1Ac gene expression, using the HD73_5014 gene promoter. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blot analysis showed that expression of the cry1Ac gene directed by the HD73_5014 gene promoter was at the same level as that directed by the previously known strongest cry promoter, P . However, this strain did not form typical bipyramidal crystals in mother cells, as observed by transmission electron microscopy and atomic force microscope. The strain with Cry1Ac protein expression under the control of the HD73_5014 gene promoter (P -cry1Ac) showed insecticidal activity against Plutella xylostella similar to that under the control of the orf1cry8E gene promoter (P -cry1Ac). Collectively, these results suggest that the HD73_5014 gene promoter, as a non-cry gene promoter, would be an efficient transcriptional element for cry gene expression. These data also show the possibility for improving Cry production by searching for transcriptional elements in not only cry genes, but also non-cry genes.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:Publisher
[do] DOI:10.1007/s00253-018-8836-5

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[PMID]: 29493231
[Au] Autor:Zhao F; Yu Y; Liu W; Zhang J; Liu X; Liu L; Yin H
[Ad] Address:Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Engineering and Technology Research Center of Food Additives , Beijing Technology and Business University , Beijing 100048 , China.
[Ti] Title:Small Molecular Weight Soybean Protein-Derived Peptides Nutriment Attenuates Rat Burn Injury-Induced Muscle Atrophy by Modulation of Ubiquitin-Proteasome System and Autophagy Signaling Pathway.
[So] Source:J Agric Food Chem;, 2018 Mar 08.
[Is] ISSN:1520-5118
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:This article describes results of the effect of dietary supplementation with small molecular weight soybean protein-derived peptides on major rat burn injury-induced muscle atrophy. As protein nutrients have been previously implicated to play an important role in improving burn injury outcomes, optimized more readily absorbed small molecular weight soybean protein-derived peptides were evaluated. Thus, the quantity, sodium dodecyl sulfate polyacrylamide-gel electrophoresis patterns, molecular weight distribution, and composition of amino acids of the prepared peptides were analyzed, and a major full-thickness 30% total body surface area burn-injury rat model was utilized to assess the impact of supplementation with soybean protein-derived peptides on initial systemic inflammatory responses as measured by interferon-gamma (IFN-γ), chemokine (C-C motif) ligand 2 (CCL2, also known as MCP-1), chemokine (C-C motif) ligand 7 (CCL7, also known as MCP-3), and generation of muscle atrophy as measured by tibialis anterior muscle (TAM) weight relative to total body weight. Induction of burn injury-induced muscle atrophy ubiquitin-proteasome system (UPS) signaling pathways in effected muscle tissues was determined by Western blot protein expression measurements of E3 ubiquitin-protein ligase TRIM-63 (TRIM63, also known as MuRF1) and F-box only protein 32 (FBXO32, also known as atrogin-1 or MAFbx). In addition, induction of burn injury-induced autophagy signaling pathways associated with muscle atrophy in effected muscle tissues was assessed by immunohistochemical analysis as measured by microtubule-associated proteins 1 light chain 3 (MAP1LC3, or commonly abbreviated as LC3) and beclin-1 (BECN1) expression, as well as relative induction of cytoplasmic-liberated form of MAP1LC3 (LC3-I) and phagophore and autophagosome membrane-bound form of MAP1LC3 (LC3-II), and BECN1 protein expression by Western blot analysis. Nutrient supplementation with small molecular weight soybean protein-derived peptides resulted a significant reduction in burn injury-induced inflammatory markers, muscle atrophy, induction of TRIM63 and FBXO32 muscle atrophy signaling pathways, and induction of autophagy signaling pathways LC3 and BECN1 associated with muscle atrophy. These results implicated that small molecular weight soybean-derived peptides dietary supplementation could be used as an adjunct therapy in burn injury management to reduce the development or severity of muscle atrophy for improved burn patient outcomes.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:Publisher
[do] DOI:10.1021/acs.jafc.7b05387

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[PMID]: 29458684
[Au] Autor:Wise MG; Horvath E; Young K; Sahm DF; Kazmierczak KM
[Ad] Address:1​International Health Management Associates, Schaumburg, Illinois, USA.
[Ti] Title:Global survey of Klebsiella pneumoniae major porins from ertapenem non-susceptible isolates lacking carbapenemases.
[So] Source:J Med Microbiol;67(3):289-295, 2018 Mar.
[Is] ISSN:1473-5644
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:PURPOSE: To understand the diversity of porin disruption in Klebsiella pneumoniae, the major outer membrane protein (OMP) porins, OmpK35 and OmpK36, were examined in a set of isolates that did not harbour traditional carbapenem-hydrolysing enzymes, but nevertheless tested non-susceptible to ertapenem. METHODS: A world-wide collection of Klebsiella pneumoniae isolates that were part of the Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance project over the years 2008-2014 were characterised with regard to their ß-lactamase gene carriage and potential permeability defects. Four hundred and eighty-seven isolates that did not carry carbapenemase genes, but were non-susceptible to ertapenem, were investigated by sequence analysis of the genes encoding OmpK35 and OmpK36. Isolates without obvious genetic lesions in either major porin gene were further examined by outer membrane protein SDS-PAGE. RESULTS: The majority of isolates, 83.0 % (404/487), exhibited clear genetic disruption in either or both of the ompK35 and ompK36 genes. Among the proportion of the collection with the highest ertapenem MIC value (>4 mg l ), 60.5 % (115/190) showed mutation in both porin genes. Isolates without obvious genetic mutations were examined by SDS-PAGE, and 90.4 % (75/83) were found to lack or show altered expression of at least one of the major OMPs when compared to an ertapenem sensitive control strain. CONCLUSION: This study illustrates that porin deficiency in Klebsiella pneumoniae is a widespread phenomenon, and in combination with ESBLs and/or AmpC enzymes, likely accounts for the elevated ertapenem MICs observed in this study.
[Mh] MeSH terms primary: Anti-Bacterial Agents/pharmacology
Bacterial Proteins/genetics
Klebsiella pneumoniae/genetics
Porins/genetics
beta-Lactams/pharmacology
[Mh] MeSH terms secundary: Bacterial Proteins/metabolism
Carbapenems/pharmacology
DNA, Bacterial/genetics
Electrophoresis, Polyacrylamide Gel
Humans
Klebsiella Infections/epidemiology
Klebsiella Infections/microbiology
Klebsiella pneumoniae/drug effects
Klebsiella pneumoniae/isolation & purification
Klebsiella pneumoniae/metabolism
Microbial Sensitivity Tests
Mutation
beta-Lactamases/genetics
beta-Lactamases/metabolism
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (Anti-Bacterial Agents); 0 (Bacterial Proteins); 0 (Carbapenems); 0 (DNA, Bacterial); 0 (OmpK35 porin, Klebsiella pneumoniae); 0 (OmpK36 protein, Klebsiella pneumoniae); 0 (Porins); 0 (beta-Lactams); EC 3.5.2.6 (beta-Lactamases); EC 3.5.2.6 (carbapenemase); G32F6EID2H (ertapenem)
[Em] Entry month:1803
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[Js] Journal subset:IM
[Da] Date of entry for processing:180221
[St] Status:MEDLINE
[do] DOI:10.1099/jmm.0.000691

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[PMID]: 29336000
[Au] Autor:Austin CE; March RE; Stock NL; Murray DL
[Ad] Address:Environmental and Life Sciences, Trent University, Peterborough, ON, Canada. caylaaustin@trentu.ca.
[Ti] Title:The Origin and Ecological Function of an Ion Inducing Anti-Predator Behavior in Lithobates Tadpoles.
[So] Source:J Chem Ecol;44(2):178-188, 2018 Feb.
[Is] ISSN:1573-1561
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:In aquatic environments, chemical cues are believed to be associated with prey response to predation risk, yet few basic cue compositions are known despite the pronounced ecological and evolutionary significance of such cues. Previous work indicated that negatively-charged ions of m/z 501 are possibly a kairomone that induces anti-predator responses in amphibian tadpoles. However, work described here confirms that this specific ion species m/z 501.2886 is produced by injured tadpoles, exhibits increased spectral intensity with higher tadpole biomass, and is not produced by starved predators. These results indicate the anion is an alarm cue released from tadpoles. High resolution mass spectrometry (HR-MS) revealed a unique elemental composition for [M-H] , m/z 501.2886, of C H O S which could not be determined in previous studies using low resolution instruments. Collision induced dissociation of m/z 501 ions formed product ions of m/z 97 and m/z 80, HSO and SO , respectively, showing the presence of sulfate. Green frog tadpoles, Lithobates clamitans, exposed to the m/z 501 anion or sodium dodecyl sulfate exhibited similar anti-predator responses, suggesting organic sulfate is a tadpole behavior modifier.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:In-Process
[do] DOI:10.1007/s10886-018-0925-5

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[PMID]: 29269282
[Au] Autor:Innocenzi V; Prisciandaro M; Tortora F; Mazziotti di Celso G; Vegliò F
[Ad] Address:University of L'Aquila, Dept. of Industrial and Information Engineering and of Economics, Viale Giovanni Gronchi 18, 67100 L'Aquila, Italy. Electronic address: valentina.innocenzi1@univaq.it.
[Ti] Title:Treatment of WEEE industrial wastewaters: Removal of yttrium and zinc by means of micellar enhanced ultra filtration.
[So] Source:Waste Manag;74:393-403, 2018 Apr.
[Is] ISSN:1879-2456
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:In this paper, the efficiency of micellar enhanced ultrafiltration technique (MEUF) was tested for the removal of yttrium and zinc ions from synthetic industrial liquid wastes. UF membranes (monotubular ceramic membranes of 210 kDa and 1 kDa molecular weight cut-off) were used with adding an anionic surfactant, sodium dodecyl sulfate (SDS). A two - level full factorial design was performed in order to evaluate the effect of molecular weight cut-off, sodium dodecyl sulfate concentration and pressure on the permeate flux and rejection yields. It was found that the single factors presented the largest influence on the permeate flux: the membrane pore size and the pressure had positive effect, instead the SDS had negative effect. Regarding the metal rejection yields the main relevant factors were the membrane pore size with a negative effect, followed by the surfactant concentration with a positive effect. The effect of the pressure seemed to be almost negligible, for zinc removal experiments had a positive effect in the interactions with the surfactant and membrane pore size. The results showed that very good removal percentages up to 99% were achieved for both metals under the following conditions: 1 kDa membrane MWCO, in the presence of the surfactant at a concentration above CMC independently of the investigated pressure.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1712
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:In-Process

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[PMID]: 29267499
[Au] Autor:Santos APP; Silva MDS; Costa EVL; Rufino RD; Santos VA; Ramos CS; Sarubbo LA; Porto ALF
[Ad] Address:Departamento de Morfologia e Fisiologia Animal, Universidade Federal Rural de Pernambuco, Recife, PE, Brasil.
[Ti] Title:Production and characterization of a biosurfactant produced by Streptomyces sp. DPUA 1559 isolated from lichens of the Amazon region.
[So] Source:Braz J Med Biol Res;51(2):e6657, 2017 Dec 11.
[Is] ISSN:1414-431X
[Cp] Country of publication:Brazil
[La] Language:eng
[Ab] Abstract:Surfactants are amphipathic compounds containing both hydrophilic and hydrophobic groups, capable to lower the surface or interfacial tension. Considering the advantages of the use of biosurfactants produced by microorganisms, the aim of this paper was to develop and characterize a biosurfactant produced by Streptomyces sp. DPUA1559 isolated from lichens of the Amazon region. The microorganism was cultured in a mineral medium containing 1% residual frying soybean oil as the carbon source. The kinetics of biosurfactant production was accompanied by reducing the surface tension of the culture medium from 60 to values around 27.14 mN/m, and by the emulsification index, which showed the efficiency of the biosurfactant as an emulsifier of hydrophobic compounds. The yield of the isolated biosurfactant was 1.74 g/L, in addition to the excellent capability of reducing the surface tension (25.34 mN/m), as observed from the central composite rotational design when the biosurfactant was produced at pH 8.5 at 28°C. The critical micelle concentration of the biosurfactant was determined as 0.01 g/mL. The biosurfactant showed thermal and pH stability regarding the surface tension reduction, and tolerance under high salt concentrations. The isolated biosurfactant showed no toxicity to the micro-crustacean Artemia salina, and to the seeds of lettuce (Lactuca sativa L.) and cabbage (Brassica oleracea L.). The biochemistry characterization of the biosurfactant showed a single protein band, an acid character and a molecular weight around 14.3 kDa, suggesting its glycoproteic nature. The results are promising for the industrial application of this new biosurfactant.
[Mh] MeSH terms primary: Lichens/microbiology
Streptomyces/metabolism
Surface-Active Agents/metabolism
[Mh] MeSH terms secundary: Analysis of Variance
Colony Count, Microbial
Culture Media
Electrophoresis, Polyacrylamide Gel
Fermentation
Hydrogen-Ion Concentration
Reference Values
Seeds/drug effects
Soybean Oil/chemistry
Spectroscopy, Fourier Transform Infrared
Streptomyces/growth & development
Streptomyces/isolation & purification
Surface Tension
Surface-Active Agents/analysis
Surface-Active Agents/chemistry
Temperature
Time Factors
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (Culture Media); 0 (Surface-Active Agents); 8001-22-7 (Soybean Oil)
[Em] Entry month:1803
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[Js] Journal subset:IM
[Da] Date of entry for processing:171222
[St] Status:MEDLINE

  10 / 153748 MEDLINE  
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[PMID]: 29517817
[Au] Autor:Deh K; Ponath GD; Molvi Z; Parel GT; Gillen KM; Zhang S; Nguyen TD; Spincemaille P; Ma Y; Gupta A; Gauthier SA; Pitt D; Wang Y
[Ad] Address:Department of Radiology, Weill Cornell Medicine, New York, New York, USA.
[Ti] Title:Magnetic susceptibility increases as diamagnetic molecules breakdown: Myelin digestion during multiple sclerosis lesion formation contributes to increase on QSM.
[So] Source:J Magn Reson Imaging;, 2018 Mar 08.
[Is] ISSN:1522-2586
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: The pathological processes in the first weeks of multiple sclerosis (MS) lesion formation include myelin digestion that breaks chemical bonds in myelin lipid layers. This can increase lesion magnetic susceptibility, which is a potentially useful biomarker in MS patient management, but not yet investigated. PURPOSE: To understand and quantify the effects of myelin digestion on quantitative susceptibility mapping (QSM) of MS lesions. STUDY TYPE: Histological and QSM analyses on in vitro models of myelin breakdown and MS lesion formation in vivo. POPULATION/SPECIMENS: Acutely demyelinating white matter lesions from MS autopsy tissue were stained with the lipid dye oil red O. Myelin basic protein (MBP), a major membrane protein of myelin, was digested with trypsin. Purified human myelin was denatured with sodium dodecyl sulfate (SDS). QSM was performed on phantoms containing digestion products and untreated controls. In vivo QSM was performed on five MS patients with newly enhancing lesions, and then repeated within 4 weeks. FIELD STRENGTH/SEQUENCE: 3D T2*-weighted spoiled multiecho gradient echo scans performed at 3T. ASSESSMENT: Region of interest analyses were performed by a biochemist and a neuroradiologist to determine susceptibility changes on in vitro and in vivo QSM images. STATISTICAL TESTS: Not applicable. RESULTS: MBP degradation by trypsin increased the QSM measurement by an average of 112 ± 37 ppb, in excellent agreement with a theoretical estimate of 111 ppb. Degradation of human myelin by SDS increased the QSM measurement by 23 ppb. As MS lesions changed from gadolinium enhancing to nonenhancing over an average of 30.6 ± 3.0 days, their susceptibility increased by an average of 7.5 ± 6.3 ppb. DATA CONCLUSION: Myelin digestion in the early stages of MS lesion formation contributes to an increase in tissue susceptibility, detectable by QSM, as a lesion evolves from gadolinium enhancing to nonenhancing. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:Publisher
[do] DOI:10.1002/jmri.25997


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