共查询到20条相似文献,搜索用时 31 毫秒
1.
G Giegerich M Pette K Fujita H Wekerle J T Epplen A Hinkkanen 《Journal of chromatography. A》1990,528(1):79-90
Reversed-phase high-performance liquid chromatography was applied to isolate myelin basic protein from human brain, followed by separation of proteolytic peptides thereof on the same chromatographic system. Brain tissue was delipidated under conditions that keep copurifying proteases inactive. The crude brain protein fraction was applied directly to a C4 column. The homogeneous protein obtained in this way was digested with thrombin and endoproteinase Lys-C in order to produce short defined myelin basic protein peptides. The purified peptides were used to determine the antigen fine specificity of myelin basic protein recognizing T lymphocyte lines isolated from multiple sclerosis patients. 相似文献
2.
Ruben Ceuppens Debora Dumont Leen Van Brussel Babs Van de Plas Ruth Daniels Jean-Paul Noben Peter Verhaert Estel Van der Gucht Johan Robben Stefan Clerens Lutgarde Arckens 《International journal of mass spectrometry》2007,260(2-3):185
One of the newly developed imaging mass spectrometry (IMS) technologies utilizes matrix-assisted laser desorption/ionization (MALDI) mass spectrometry to map proteins in thin tissue sections. In this study, we evaluated the power of MALDI IMS as we developed it in our (Bruker) MALDI TOF (Reflex IV) and TOF-TOF (Ultraflex II) systems to study myelin patterns in the mouse central nervous system under normal and pathological conditions. MALDI IMS was applied to assess myelin basic protein (MBP) isoform-specific profiles in different regions throughout the mouse brain. The distribution of ions of m/z 14,144 and 18,447 displayed a striking resemblance with white matter histology and were identified as MBP isoform 8 and 5, respectively. In addition, we demonstrated a significant reduction of the MBP-8 peak intensity upon MALDI IMS analysis of focal ethidium bromide-induced demyelinated brain areas. Our MS images were validated by immunohistochemistry using MBP antibodies. This study underscores the potential of MALDI IMS to study the contribution of MBP to demyelinating diseases. 相似文献
3.
Polylactic acid (PLA) nanoparticles coated with Gd(III)‐based metallosurfactants (MS) are prepared using a simple and rapid one‐step method, flash nanoprecipitation (FNP), for magnetic resonance imaging (MRI) applications. By co‐assembling the Gd(III)‐based MS and an amphiphilic polymer, methoxy poly(ethylene glycol)‐b‐poly(?‐caprolactone) (mPEG‐b‐PCL), PLA cores were rapidly encapsulated to form biocompatible T1 contrast agents with tunable particle size and narrow size distribution. The hydrophobic property of Gd(III)‐based MS were finely tuned to achieve their high loading efficiency. The size of the nanoparticles was easily controlled by tuning the stream velocity, Reynolds number and the amount of the amphiphilic block copolymer during the FNP process. Under the optimized condition, the relaxivity of the nanoparticles was achieved up to 35.39 mM?1 s?1 (at 1.5 T), which is over 8 times of clinically used MRI contrast agents, demonstrating the potential application for MR imaging. 相似文献
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Kim T Momin E Choi J Yuan K Zaidi H Kim J Park M Lee N McMahon MT Quinones-Hinojosa A Bulte JW Hyeon T Gilad AA 《Journal of the American Chemical Society》2011,133(9):2955-2961
Mesoporous silica-coated hollow manganese oxide (HMnO@mSiO(2)) nanoparticles were developed as a novel T(1) magnetic resonance imaging (MRI) contrast agent. We hypothesized that the mesoporous structure of the nanoparticle shell enables optimal access of water molecules to the magnetic core, and consequently, an effective longitudinal (R(1)) relaxation enhancement of water protons, which value was measured to be 0.99 (mM(-1)s(-1)) at 11.7 T. Adipose-derived mesenchymal stem cells (MSCs) were efficiently labeled using electroporation, with much shorter T(1) values as compared to direct incubation without electroporation, which was also evidenced by signal enhancement on T(1)-weighted MR images in vitro. Intracranial grafting of HMnO@mSiO(2)-labeled MSCs enabled serial MR monitoring of cell transplants over 14 days. These novel nanoparticles may extend the arsenal of currently available nanoparticle MR contrast agents by providing positive contrast on T(1)-weighted images at high magnetic field strengths. 相似文献
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以两种夹心型锰杂多配合物K10[Mn4(PW9O34)2]·22H2O和Na16[Mn4(H2O)2(P2W15O56)2]·53H2O作为研究对象, 采用元素分析和红外光谱对其结构进行了表征, 测试其在水中、牛血清白蛋白及运铁蛋白溶液中的弛豫效率, 并进行了大鼠活体成像实验. 结果表明, 这两种锰杂多配合物的弛豫效率高于或接近于目前临床常用的造影剂Gd-DTPA, 对肝脏和肾脏MRI信号具有良好的增强效果, 是比较好的潜在磁共振成像造影剂候选化合物. 相似文献
8.
Strauch RC Mastarone DJ Sukerkar PA Song Y Ipsaro JJ Meade TJ 《Journal of the American Chemical Society》2011,133(41):16346-16349
Contrast agents for magnetic resonance imaging are frequently employed as experimental and clinical probes. Drawbacks include low signal sensitivity, fast clearance, and nonspecificity that limit efficacy in experimental imaging. In order to create a bioresponsive MR contrast agent, a series of four Gd(III) complexes targeted to the HaloTag reporter were designed and synthesized. HaloTag is unique among reporter proteins for its specificity, versatility, and the covalent interaction between substrate and protein. In similar systems, these properties produce prolonged in vivo lifetimes and extended imaging opportunities for contrast agents, longer rotational correlation times, and increases in relaxivity (r(1)) upon binding to the HaloTag protein. In this work we report a new MR contrast probe, 2CHTGd, which forms a covalent bond with its target protein and results in a dramatic increase in sensitivity. A 6-fold increase in r(1), from 3.8 to 22 mM(-1) s(-1), is observed upon 2CHTGd binding to the target protein. This probe was designed for use with the HaloTag protein system which allows for a variety of substrates (specific for MRI, florescence, or protein purification applications) to be used with the same reporter. 相似文献
9.
Long-circulating gadolinium-loaded liposomes: potential use for magnetic resonance imaging of the blood pool 总被引:2,自引:0,他引:2
In our previous paper, we reported a method of liposome loading with Gadolinium (Gd) via so called polychelating amphiphilic polymer (PAP). A novel Gd-containing polymeric probe, suitable for the incorporation into the liposomal membrane, was prepared from a low-molecular-weight DTPA-polylysine by linking its N-terminus to a lipid anchor, NGPE-PE. When compared with known membranotropic MR probes, such as Gd-DTPA-SA and Gd-DTPA-PE, liposomes containing new membrane-bound polychelator possess enhanced relaxivity for water protons resulting in an increase of tissue signal intensity on MR images. In this study, we developed the optimized protocol to prepare a liposomal MR contrast agent with high relaxivity and narrow size distribution. Gd-containing liposomes were additionally modified with PEG to provide longevity in vivo. We also demonstrated that upon intravenous administration in rabbit and dog, the new preparation causes a prolonged decrease in the blood T1 value (reflecting the proton relaxation rate in the blood) and may be considered as a potential contrast agent for MRI of the blood pool. 相似文献
10.
Jiamei Han Dr. Guohai Liang Prof. Da Xing 《Chemistry (Weinheim an der Bergstrasse, Germany)》2019,25(35):8353-8362
Accurate diagnosis of tumor characteristics, including its location and boundary, is of immense value to subsequent therapy. Activatable magnetic resonance imaging (MRI) contrast agents that respond to tumor-specific microenvironments, such as the redox state, pH, and enzyme activity, enable better mapping of tumor tissue. However, the practical application of most reported activatable agents is hampered by problems including potential toxicity, inefficient elimination, and slow activation. In this study, we developed a zwitterionic iron complex (Fe-ZDS) as a positive MRI contrast agent for tumor-specific imaging. Fe-ZDS could dissociate in weakly acidic solution rapidly, accompanied by clear longitudinal relaxivity (r1) enhancement, which enabled the complex to act as a pH-sensitive contrast agent for tumor-specific MR imaging. In vivo experiments showed that Fe-ZDS rapidly enhanced the tumor-to-normal contrast ratio by >40 %, which assisted in distinguishing the tumor boundary. Furthermore, Fe-ZDS circulated freely in the bloodstream and was excreted relatively safely via kidneys owing to its zwitterionic nature. Therefore, Fe-ZDS is an ideal candidate for a tumor-specific MRI contrast agent and holds considerable potential for clinical translation. 相似文献
11.
The fast Padé transform (FPT) has been benchmarked as a stable, high-resolution processor. In this paper, the performance
of the FPT is examined for in vitro magnetic resonance (MR) spectroscopic data associated with ovarian, breast and prostate
cancer as well as benign or normal tissue. We also examine how the FPT handles in vivo MR spectroscopic (MRS) time signals
from human brain encoded by high field and clinical (1.5 T) scanners. Salient comparisons are made with the conventional data
analysis through the fast Fourier transform (FFT). Separation of noise from genuine signal is carried out with a view to practical
applications. Compared to the FFT, the fast Padé transform provided markedly improved resolution of total shape spectra from
encoded in vivo time signals from healthy human brain and for in vitro data associated with ovarian cancer. Evidence is presented
as to why it is necessary to go beyond MR total shape spectra to calculate metabolite concentrations. It is shown that error
spectra, while necessary, are insufficient for accurate assessment of MR data. Two examples from oncology are given to illustrate
this point: (1) a marker of breast cancer, phosphocholine, is detected on the component shape spectra, but not on the total
shape spectrum, (2) diagnostically important multiplet resonances in prostate cancer spectra can only be detected on the component
shape spectra, but not on the total shape spectrum. The FPT provides accurate calculation of metabolite concentrations based
on in vitro MR data from three diagnostic problems in clinical oncology: (1) malignant and benign ovarian lesions, (2) breast
cancer, fibroadenoma and normal breast tissue and (3) prostate cancer tissue, healthy glandular and stromal prostate tissue.
Practical implementation of signal-noise separation is demonstrated for MR time signals encoded in vivo from the human brain
on a clinical (1.5 T) scanner. Some 23 stable resonances are thereby identified and quantified. These results provide the
basis for the needed next steps: to extensively apply the FPT to in vivo time signals encoded mainly on clinical scanners
from e.g. brain tumors, breast, ovary and prostate cancers as well as from benign and normal tissue. The overall goal is that
this practical approach through mathematical optimization enables Padé-based MRS to soon be implemented in clinical oncology,
including target planning, post-radiotherapeutic follow-up and other aspects of radiation therapy. 相似文献
12.
Zamfir AD Serb A Vukeli Ž Flangea C Schiopu C Fabris D Kalanj-Bognar S Capitan F Sisu E 《Journal of the American Society for Mass Spectrometry》2011,22(12):2145-2159
Gangliosides (GGs), sialic acid-containing glycosphingolipids, are known to be involved in the invasive/metastatic behavior
of brain tumor cells. Development of modern methods for determination of the variations in GG expression and structure during
neoplastic cell transformation is a priority in the field of biomedical analysis. In this context, we report here on the first
optimization and application of chip-based nanoelectrospray (NanoMate robot) mass spectrometry (MS) for the investigation
of gangliosides in a secondary brain tumor. In our work a native GG mixture extracted and purified from brain metastasis of
lung adenocarcinoma was screened by NanoMate robot coupled to a quadrupole time-of-flight MS. A native GG mixture from an
age-matched healthy brain tissue, sampled and analyzed under identical conditions, served as a control. Comparative MS analysis
demonstrated an evident dissimilarity in GG expression in the two tissue types. Brain metastasis is characterized by many
species having a reduced N-acetylneuraminic acid (Neu5Ac) content, however, modified by fucosylation or O-acetylation such as Fuc-GM4, Fuc-GM3, di-O-Ac-GM1, O-Ac-GM3. In contrast, healthy brain tissue is dominated by longer structures exhibiting from mono- to hexasialylated sugar
chains. Also, significant differences in ceramide composition were discovered. By tandem MS using collision-induced dissociation
at low energies, brain metastasis-associated GD3 (d18:1/18:0) species as well as an uncommon Fuc-GM1 (d18:1/18:0) detected
in the normal brain tissue could be structurally characterized. The novel protocol was able to provide a reliable compositional
and structural characterization with high analysis pace and at a sensitivity situated in the fmol range. 相似文献
13.
<正>超顺磁性氧化铁(Superparamagnetic iron oxide,SPIO)作为医用磁共振成像(Magnetic resonance imaging,MRI)造影剂,可以有效地改变人体组织中质子的自旋-自旋弛豫时间,从而增强磁共振成像的对 相似文献
14.
Gangliosides are particularly abundant in the nervous system (NS) where their pattern and structure in a certain milieu or a defined region exhibit a pronounced specificity. Since gangliosides are useful biomarkers for diagnosis of NS ailments, a clear-cut mapping of individual components represents a prerequisite for designing ganglioside-based diagnostic procedures, treatments, or vaccines. These bioclinical aspects and the high diversity of ganglioside species claim for development of specific analytical strategies. This review summarizes the state-of-the-art in the implementation of separation techniques and microfluidics coupled to MS, which have contributed significantly to the advancement of the field. In the first part, the review discusses relevant approaches based on HPLC MS and CE coupled to ESI MS and their applications in the characterization of gangliosides expressed in healthy and diseased NS. A considerable section is dedicated to microfluidics MS and ion mobility separation MS, developed for the study of brain gangliosidome and its changes triggered by various factors, as well as for ganglioside biomarker discovery in neurodegenerative diseases and brain cancer. In the last part of the review, the benefits and perspectives in ganglioside research of these high-performance techniques are presented. 相似文献
15.
Spatially Resolved Quantification of Gadolinium(III)‐Based Magnetic Resonance Agents in Tissue by MALDI Imaging Mass Spectrometry after In Vivo MRI 下载免费PDF全文
Dr. Michaela Aichler Katharina Huber Dr. Franz Schilling Dr. Fabian Lohöfer Dr. Katja Kosanke Dr. Reinhard Meier Prof.Dr. Ernst J. Rummeny Prof. Dr. Axel Walch Dr. Moritz Wildgruber 《Angewandte Chemie (International ed. in English)》2015,54(14):4279-4283
Gadolinium(III)‐based contrast agents improve the sensitivity and specificity of magnetic resonance imaging (MRI), especially when targeted contrast agents are applied. Because of nonlinear correlation between the contrast agent concentration in tissue and the MRI signal obtained in vivo, quantification of certain biological or pathophysiological processes by MRI remains a challenge. Up to now, no technology has been able to provide a spatially resolved quantification of MRI agents directly within the tissue, which would allow a more precise verification of in vivo imaging results. MALDI imaging mass spectrometry for spatially resolved in situ quantification of gadolinium(III) agents, in correlation to in vivo MRI, were evaluated. Enhanced kinetics of Gadofluorine M were determined dynamically over time in a mouse model of myocardial infarction. MALDI imaging was able to corroborate the in vivo imaging MRI signals and enabled in situ quantification of the gadolinium probe with high spatial resolution. 相似文献
16.
Intracellular Ca(2+) plays an important role in signal transduction, and we are developing new MRI techniques to study its regulation in living animals. We have reported on an MRI contrast agent (DOPTA-Gd) where the relaxivity of the complex is controlled by the presence or absence of the divalent ion Ca(2+). By structurally modulating inner-sphere access of water to a chelated Gd(3+) ion, we observe a substantial and reversible change in T(1) upon the addition of Ca(2+) and not other divalent ions. Luminescence lifetime and NMRD measurements of the complex have been acquired, and several parameters contribute to the Ca(2+) dependent relaxivity change of DOPTA-Gd. The number of inner-sphere water molecules is more than doubled after the Ca(2+) concentration is increased. This finding strongly supports the proposed conformational change of DOPTA-Gd when Ca(2+) is bound. Relaxometric measurements confirm these results and provide an indication that second-sphere water molecules are probably responsible for paramagnetic relaxation enhancement in the absence of Ca(2+). After Ca(2+) is bound to DOPTA-Gd, the molecule undergoes a substantial conformational change that opens up the hydrophilic face of the tetraazacyclododecane macrocycle. This change dramatically increases the accessibility of chelated Gd(3+) ion to bulk solvent. The design of this class of calcium-activated MR contrast agent was based primarily on the assumption that the number of coordinated inner-sphere water molecules would be the dominating factor in observed relaxivity measurements. This result has been confirmed; however, careful mechanistic studies reveal that additional factors are involved in this process. 相似文献
17.
Gero P. Hooff Nina Patel W. Gibson Wood Walter E. Müller Gunter P. Eckert Dietrich A. Volmer 《Analytical and bioanalytical chemistry》2010,398(4):1801-1808
The isoprenoids farnesyl-(FPP) and geranylgeranylpyrophosphate (FPP and GGPP) are two major lipid intermediates in the mevalonate
pathway. They participate in post-translational modification of members of the superfamily of small guanosine triphosphatases
(GTPases; Ras, Rab, Rac, etc.) via prenylation reactions. Due to the important role of these proteins in a number of cell
processes, in particular cell growth, division, and differentiation, investigation of the involvement of isoprenoids in these
processes is of great interest. In a previously published report, we described a fully validated assay for the quantitation
of the two isoprenoids using a high-performance liquid chromatography (HPLC)–fluorescence detection (FLD) method. The current
work expands on the previous method and enhances it greatly by using a much faster state-of-the-art ultrahigh-performance
liquid chromatography (UHPLC) technique coupled to tandem mass spectrometry (MS/MS). The method exhibited a linear concentration
range of 5–250 ng/mL for FPP and GGPP in human brain tissue; it was shown to be unaffected by ion suppression and provided
results almost six times faster than the HPLC–FLD assay. Comparison of UHPLC–MS/MS and HPLC–FLD yielded excellent comparability
of the two assays for both isoprenoids. Based on the UHPLC–MS/MS assay, a novel in vitro test system was implemented to study
enzyme specificity for distinct amino acid CAAX motifs, which is potentially useful for investigating target interactions
of new therapeutics for diseases involving pathological regulation of isoprenoids and/or small GTPases. 相似文献
18.
Brigitte Gillet Chrystelle Po Damien Dupont Catherine Sébrié Philippe Méric 《Comptes Rendus Chimie》2010,13(4):459-465
Divalent manganese ion Mn2+ is paramagnetic and has played an important role in the history of Nuclear Magnetic Resonance and in Magnetic Resonance imaging (MRI). In another way it can be taken up by neurons as an analog to Ca2+. So, particular interest in the use of Mn2+ stems from its potential as an MRI contrast for cerebral studies on normal rodent and on experimental models of diseases. This work presents the three major classes of applications of the Manganese-Enhanced Magnetic Resonance Imaging (MEMRI) for brain experimental studies. The utility of MEMRI method for following development of the brain in physiological and pathological states is particularly pointed out. 相似文献
19.
Jianfeng Ma Ting Li Huiyao Chen Chengde Wang Haixing Wang Qun Li 《Electrophoresis》2021,42(19):1965-1973
Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor in the central nervous system. GBM patients have a very low 5-year survival rate and most of them died within 1 year. Conventional histopathological examination for GBM diagnosis is complicated and time-consuming, which always blocks the development of more precise and effective treatments in resection operation. Rapid evaporative ionization mass spectrometry (REIMS) is a MS technique in clinical medicine research, which combines the common diathermy device with MS to acquire the lipid profiles of tissue specimens for lipidomic analysis and real-time tumor diagnosis. In this study, the REIMS method employing bipolar forceps was optimized and validated for high-throughput lipidomics and diagnosis of GBM for the first time. Total 42 lipid metabolites were tentatively identified and 12 out of 13 lipid biomarkers showed higher intensities in GBM, which were consistent with previous studies. After this, a statistic model was built with the lipidomic data for the diagnosis of GBM tumor in real-time. The diagnostic accuracy (94.74%), sensitivity (95.38%), and specificity (93.33%) were evaluated with histopathology validated brain tissue specimens that were not used in the training set. The proposed REIMS method for the lipidomic-analysis and diagnosis of GBM tumor provides a new direction for MS-based lipidomics and precision medicine and might be used to guide surgeons to precisely resect the GBM tissue and keep the normal brain tissue in operation. 相似文献
20.
Dr. Lorena García-Hevia Dr. Manuel Bañobre-López Dr. Juan Gallo 《Chemistry (Weinheim an der Bergstrasse, Germany)》2019,25(2):431-441
Manganese-based nanostructured contrast agents (CAs) entered the field of medical diagnosis through magnetic resonance imaging (MRI) some years ago. Although some of these Mn-based CAs behave as classic T1 contrast enhancers in the same way as clinical Gd-based molecules do, a new type of Mn nanomaterials have been developed to improve MRI sensitivity and potentially gather new functional information from tissues by using traditional T1 contrast enhanced MRI. These nanomaterials have been designed to respond to biological environments, mainly to pH and redox potential variations. In many cases, the differences in signal generation in these responsive Mn-based nanostructures come from intrinsic changes in the magnetic properties of Mn cations depending on their oxidation state. In other cases, no changes in the nature of Mn take place, but rather the nanomaterial as a whole responds to the change in the environment through different mechanisms, including changes in integrity and hydration state. This review focusses on the chemistry and MR performance of these responsive Mn-based nanomaterials. 相似文献