The Experts below are selected from a list of 54141 Experts worldwide ranked by ideXlab platform
Leo L Cheng - One of the best experts on this subject based on the ideXlab platform.
-
high resolution magic angle spinning hrmas nmr methods in metabolomics
Methods of Molecular Biology, 2019Co-Authors: Marlon Tilgner, Tim S Vater, Piet Habbel, Leo L ChengAbstract:High-resolution magic angle spinning (HRMAS) NMR spectroscopy enables the evaluation of metabolite profiles of Intact Tissue with high spectral resolution. The ability to preserve the Tissue after analysis permits subsequent histopathological examination and enables the analyses of correlations between Tissue metabolites and pathologies, thus making HRMAS NMR spectroscopy a powerful tool in the metabolomics field. Improved methods for the elimination of spinning sidebands that appear at low spinning rates preserve the integrity of Tissue structures better and allow measurement of delicate Tissues, such as clinical biopsy core samples. In the metabolomics field, HRMAS NMR has been established as a valuable tool for both untargeted and targeted metabolite profiling. In this chapter, we present protocols to perform HRMAS NMR spectroscopy experiments, including sample preparation, acquisition procedures, measurement parameters, histopathological examination techniques, spectral processing, and metabolite quantification and statistical analyses.
-
assessing prostate cancer growth with citrate measured by Intact Tissue proton magnetic resonance spectroscopy
Prostate Cancer and Prostatic Diseases, 2012Co-Authors: R Dittrich, Johannes Kurth, Emily A Decelle, Elita M Defeo, M Taupitz, W S Mcdougal, Leo L ChengAbstract:Annual PSA tests have led to a significant increase in the number of prostate cancer (PCa) cases diagnosed. This increased incidence has led to overtreatment of many patients, as current pathology often cannot distinguish latent from aggressive PCa. Studies have shown that the depletion of zinc in prostate cells correlated with cell-line growth rates, and may therefore relate to the progression of PCa. Furthermore, as zinc is normally an inhibitor of citrate oxidation, the reduction of zinc in PCa may cause a decrease in citrate secretion levels in the glandular epithelia of PCa patients. Using high-resolution magic angle spinning proton magnetic resonance spectroscopy followed by quantitative histopathology, we investigate unit histo-benign prostate epithelial citrate concentrations in Intact Tissue samples obtained from 18 patients with pre-surgical PSA values less than 20 ng/ml. Using these data, we evaluate correlations between citrate concentrations and PSA velocities, densities and blood percent-free PSA. We observe different linear patterns between citrate concentrations and histo-benign glandular epithelia from patients of different PSA velocities. More importantly, we obtain a significant correlation between PSA velocity, density and percent-free PSA, and citrate concentrations in unit volume of histo-benign epithelial glands of the peripheral zone. Low levels of citrate in unit volume represent rapidly increasing PSA values, and, therefore, may be used as an indicator of fast-growing PCa. Thus, Tissue samples obtained at the time of biopsy may be evaluated for their citrate concentrations for the prediction of PCa growth rates, allowing for the implementation of alternative treatment options and reducing overtreatment.
-
metabolomic characterization of human rectal adenocarcinoma with Intact Tissue magnetic resonance spectroscopy
Diseases of The Colon & Rectum, 2009Co-Authors: Kate W Jordan, Johan Nordenstam, Gregory Y Lauwers, David A Rothenberger, Karim Alavi, Michael Garwood, Leo L ChengAbstract:Rectal cancers account for approximately one-third of colorectal malignancies, and the estimated number of cases for 2008 is 40,740.1 The expected overall five-year survival rate for patients with a diagnosis of rectal cancer is 65 percent in the United States, according to the National Cancer Institute.2 Despite known prognostic factors and new and improved diagnostic methods, the severity of cancer stage is frequently underestimated.3 Accurate diagnosis, staging, and management of the disease are crucial for achieving optimal outcomes. Currently, although histopathologic evaluation of biopsy samples can achieve most of these goals, radiologic tests such as computed tomography (CT), ultrasonography (US), positron emission tomography (PET), and magnetic resonance imaging (MRI) are unable to differentiate malignant from benign Tissue with sufficient accuracy to be clinically useful for noninvasive diagnosis. The preoperative staging of the tumor is usually done according to the TNM system by using MRI, endorectal US, CT, or a combination of these tests to assess the tumor itself, whether it has spread to locoregional lymph nodes, and whether distant metastases are present.4, 5 The diagnosis of rectal cancer is currently dependent on biopsies taken from the suspicious lesion during colonoscopic or sigmoidoscopic examinations. Although histopathology will remain the standard for the diagnosis of rectal cancer for years to come, it is desirable to develop new technologies that not only can detect suspicious sites on direct biopsy, but may even replace histopathology to achieve diagnosis and grading of rectal cancer tumors noninvasively in vivo. Feasible techniques currently being examined for their potential roles in cancer management are those that probe the underlying biochemistry accompanying malignant changes, such as magnetic resonance spectroscopy (MRS). High-resolution magic angle spinning (HRMAS) proton (1H) MRS is one such technique developed for the metabolomic analysis of Intact Tissues.6, 7 The HRMAS 1HMRS technique allows acquisition of highly resolved spectra from unaltered Tissue samples, while preserving Tissue histopathologic architecture for histopathologic analysis. Since its development, several groups, including our own, have shown the ability of this technique to differentiate malignant from benign samples of various Tissues and to accurately characterize the bioactivity and, therefore aggressiveness, of tumors.8, 9 The aim of the present study was to test the efficacy of the HRMAS 1HMRS technique in differentiating malignant rectal cancer from benign cells by measuring the metabolic profile of rectal tumor biopsy samples and comparing them with benign rectal mucosa samples from the same patients.
-
reduction of spinning sidebands in proton nmr of human prostate Tissue with slow high resolution magic angle spinning
Magnetic Resonance in Medicine, 2005Co-Authors: Melissa A Burns, Jennifer L Taylor, Andrea G Zepeda, Anthony Bielecki, David G Cory, Leo L ChengAbstract:High-resolution magic angle spinning (HRMAS) NMR spectroscopy has proven useful for analyzing Intact Tissue and permitting correlations to be made between Tissue metabolites and disease pathologies. Extending these studies to slow-spinning methodologies helps protect Tissue pathological structures from HRMAS centrifuging damage and may permit the study of larger objects. Spinning sidebands (SSBs), which are produced by slow spinning, must be suppressed to prevent the complication of metabolic spectral regions. In this study human prostate Tissues, as well as gel samples of a metabolite mixture solution, were measured with continuous-wave (CW) water presaturation on a 14.1T spectrometer, with HRMAS spinning rates of 250, 300, 350, 600, and 700 Hz, and 3.0 kHz. Editing the spectra by means of a simple minimum function (Min(A, B, ..., N) for N spectra acquired at different but close spinning rates) produced SSB-free spectra. Statistically significant linear correlations were observed for metabolite concentrations quantified from the Min(A, B, ..., N)-edited spectra generated at low spinning rates, with concentrations measured from the 3 kHz spectra, and also with quantitative pathology. These results indicate the empirical utility of this scheme for analyzing Intact Tissue, which also may be used as an adjunct tool in pathology for diagnosing disease.
Jeremy K. Nicholson - One of the best experts on this subject based on the ideXlab platform.
-
rapid diagnosis and staging of colorectal cancer via high resolution magic angle spinning nuclear magnetic resonance hr mas nmr spectroscopy of Intact Tissue biopsies
Annals of Surgery, 2014Co-Authors: Reza Mirnezami, Jeremy K. Nicholson, Elaine Holmes, Beatriz Jimenez, Jia V Li, James Kinross, Kirill Veselkov, Robert D Goldin, Ara DarziAbstract:Objective:To develop novel metabolite-based models for diagnosis and staging in colorectal cancer (CRC) using high-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy.Background:Previous studies have demonstrated that cancer cells harbor unique metabolic characterist
-
magic angle spinning nmr and 1h 31p heteronuclear statistical total correlation spectroscopy of Intact human gut biopsies
Analytical Chemistry, 2008Co-Authors: Yulan Wang, Elaine Holmes, Olivier Cloarec, Huiru Tang, John C Lindon, Sunil Kochhar, Jeremy K. NicholsonAbstract:Previously we have demonstrated the use of 1H magic angle spinning (MAS) NMR spectroscopy for the topographical variations in functional metabolic signatures of Intact human intestinal biopsy samples. Here we have analyzed a series of MAS 1H NMR spectra (spin−echo, one-dimensional, and diffusion-edited) and 31P−{1H} spectra and focused on analyzing the enhancement of information recovery by use of the statistical total correlation spectroscopy (STOCSY) method. We have applied a heterospectroscopic cross-examination performed on the same samples and between 1H and 31P−{1H} spectra (heteronuclear STOCSY) to recover latent metabolic information. We show that heterospectroscopic correlation can give new information on the molecular compartmentation of metabolites in Intact Tissues, including the statistical “isolation” of a phosphlipid/triglyceride vesicle pool in Intact Tissue. The application of 31P−1H HET-STOCSY allowed the cross-assignment of major 31P signals to their equivalent 1H NMR spectra, e.g., for...
-
High-resolution 1H NMR and magic angle spinning NMR spectroscopic investigation of the biochemical effects of 2-bromoethanamine in Intact renal and hepatic Tissue
Magnetic resonance in medicine, 2001Co-Authors: S. Garrod, Manfred Spraul, Susan C. Connor, Jeremy K. Nicholson, E. Humpher, J.c. Connelly, Elaine HolmesAbstract:The metabolic consequences of xenobiotic-induced toxicity were investigated using high-resolution magic angle spinning (MAS) NMR spectroscopy of Intact Tissue. Renal papillary necrosis (RPN) was induced in Sprague-Dawley rats (n = 12) via a single i.p. dose of 250 mg/kg 2-bromoethanamine (BEA) hydrobromide. At 2, 4, 6, and 24 h after treatment with BEA, three animals were killed and Tissue samples were obtained from liver, renal cortex, and renal medulla. Tissue samples were also removed at 2 and 24 h from matched controls (n = 6). 1H MAS NMR spectroscopic techniques were used to analyze samples of Intact Tissue (∼10 mg). Decreased levels of nonperturbing renal osmolytes (glycerophosphocholine, betaine, and myo-inositol) were observed in the renal papilla of BEA-treated animals at 6 and 24 h postdose (p.d.), concomitant with a relative increase in the Tissue concentration of creatine. Increased levels of glutaric acid were found in all Tissues studied in BEA-treated animals at 4 and 6 h p.d., indicating the inhibition of mitochondrial fatty acyl CoA dehydrogenases and mitochondrial dysfunction. Increased levels of trimethylamine-N-oxide occurred in the renal cortex at 6 h p.d. Changes in the metabolite profile of liver included an increase in the relative concentrations of triglycerides, lysine, and leucine. The novel application of 1H MAS NMR to the biochemical analysis of Intact Tissues following a toxic insult highlights the potential of this technique as a toxicological probe in providing a direct link between urinary biomarkers of toxicity and histopathological evaluation of toxicological lesions. Magn Reson Med 45:781–790, 2001. © 2001 Wiley-Liss, Inc.
-
comparison of in vivo 1h mrs of human brain tumours with 1h hr mas spectroscopy of Intact biopsy samples in vitro
Magnetic Resonance Materials in Physics Biology and Medicine, 1999Co-Authors: Sarah J Barton, Jeremy K. Nicholson, Franklyn A Howe, Andrew M Tomlins, Simon Cudlip, Anthony B Bell, John R GriffithsAbstract:High resolution magic angle spinning (MAS)1H nuclear magnetic resonance (NMR) spectroscopy has been employed to study Intact human brain tumour Tissue and comparison with the corresponding in vivo spectrum has been made. Two dimensional1H MAS-NMR measurements, including J-resolved and homonuclear shift correlation spectra, were obtained to aid metabolite signal assignment. MAS gave greatly improved line-shape and reduced line-width in comparison to conventional high resolution in vivo1H MRS of Intact Tissue, permitting the simultaneous detection of cellular lipids and metabolites. The technique provides the most direct method for comparison of in vivo spectra with high resolution spectra in vitro and hence allows more reliable peak assignment of in vivo1H MRS spectra.
Edwin E Spencer - One of the best experts on this subject based on the ideXlab platform.
-
partial thickness articular surface rotator cuff tears an all inside repair technique
Clinical Orthopaedics and Related Research, 2010Co-Authors: Edwin E SpencerAbstract:Background Treatment of partial-thickness articular surface rotator cuff tears varies from simple debridement with or without an acromioplasty to various repair techniques. These repair techniques have included in situ transtendinous methods, as well as completion of the tear and repairing the full-thickness defect. The transtendinous techniques can be associated with stiffness and completing the tear takes down normal Intact Tissue. Therefore, a technique was developed that repairs the articular-side partial- thickness rotator cuff tears with an all-inside approach that does not violate the Intact bursal Tissue and does not complete the tear.
-
partial thickness articular surface rotator cuff tears an all inside repair technique
Techniques in Shoulder and Elbow Surgery, 2007Co-Authors: Edwin E SpencerAbstract:The treatment of partial-thickness articular surface rotator cuff tears is controversial. Treatment has varied from simple debridement with or without an acromioplasty to various repair techniques. These repair techniques have included transtendinous methods and completion of the tear and repairing the full thickness defect. The transtendinous techniques can be associated with stiffness, and completing the tear takes down normal Intact Tissue. Therefore, a technique was developed that repairs the articular side partial-thickness rotator cuff tears with an all-inside approach that does not violate the Intact bursal Tissue and does not complete the tear.
Elaine Holmes - One of the best experts on this subject based on the ideXlab platform.
-
rapid diagnosis and staging of colorectal cancer via high resolution magic angle spinning nuclear magnetic resonance hr mas nmr spectroscopy of Intact Tissue biopsies
Annals of Surgery, 2014Co-Authors: Reza Mirnezami, Jeremy K. Nicholson, Elaine Holmes, Beatriz Jimenez, Jia V Li, James Kinross, Kirill Veselkov, Robert D Goldin, Ara DarziAbstract:Objective:To develop novel metabolite-based models for diagnosis and staging in colorectal cancer (CRC) using high-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy.Background:Previous studies have demonstrated that cancer cells harbor unique metabolic characterist
-
magic angle spinning nmr and 1h 31p heteronuclear statistical total correlation spectroscopy of Intact human gut biopsies
Analytical Chemistry, 2008Co-Authors: Yulan Wang, Elaine Holmes, Olivier Cloarec, Huiru Tang, John C Lindon, Sunil Kochhar, Jeremy K. NicholsonAbstract:Previously we have demonstrated the use of 1H magic angle spinning (MAS) NMR spectroscopy for the topographical variations in functional metabolic signatures of Intact human intestinal biopsy samples. Here we have analyzed a series of MAS 1H NMR spectra (spin−echo, one-dimensional, and diffusion-edited) and 31P−{1H} spectra and focused on analyzing the enhancement of information recovery by use of the statistical total correlation spectroscopy (STOCSY) method. We have applied a heterospectroscopic cross-examination performed on the same samples and between 1H and 31P−{1H} spectra (heteronuclear STOCSY) to recover latent metabolic information. We show that heterospectroscopic correlation can give new information on the molecular compartmentation of metabolites in Intact Tissues, including the statistical “isolation” of a phosphlipid/triglyceride vesicle pool in Intact Tissue. The application of 31P−1H HET-STOCSY allowed the cross-assignment of major 31P signals to their equivalent 1H NMR spectra, e.g., for...
-
High-resolution 1H NMR and magic angle spinning NMR spectroscopic investigation of the biochemical effects of 2-bromoethanamine in Intact renal and hepatic Tissue
Magnetic resonance in medicine, 2001Co-Authors: S. Garrod, Manfred Spraul, Susan C. Connor, Jeremy K. Nicholson, E. Humpher, J.c. Connelly, Elaine HolmesAbstract:The metabolic consequences of xenobiotic-induced toxicity were investigated using high-resolution magic angle spinning (MAS) NMR spectroscopy of Intact Tissue. Renal papillary necrosis (RPN) was induced in Sprague-Dawley rats (n = 12) via a single i.p. dose of 250 mg/kg 2-bromoethanamine (BEA) hydrobromide. At 2, 4, 6, and 24 h after treatment with BEA, three animals were killed and Tissue samples were obtained from liver, renal cortex, and renal medulla. Tissue samples were also removed at 2 and 24 h from matched controls (n = 6). 1H MAS NMR spectroscopic techniques were used to analyze samples of Intact Tissue (∼10 mg). Decreased levels of nonperturbing renal osmolytes (glycerophosphocholine, betaine, and myo-inositol) were observed in the renal papilla of BEA-treated animals at 6 and 24 h postdose (p.d.), concomitant with a relative increase in the Tissue concentration of creatine. Increased levels of glutaric acid were found in all Tissues studied in BEA-treated animals at 4 and 6 h p.d., indicating the inhibition of mitochondrial fatty acyl CoA dehydrogenases and mitochondrial dysfunction. Increased levels of trimethylamine-N-oxide occurred in the renal cortex at 6 h p.d. Changes in the metabolite profile of liver included an increase in the relative concentrations of triglycerides, lysine, and leucine. The novel application of 1H MAS NMR to the biochemical analysis of Intact Tissues following a toxic insult highlights the potential of this technique as a toxicological probe in providing a direct link between urinary biomarkers of toxicity and histopathological evaluation of toxicological lesions. Magn Reson Med 45:781–790, 2001. © 2001 Wiley-Liss, Inc.
Tone Frost Bathen - One of the best experts on this subject based on the ideXlab platform.
-
metabolic portraits of breast cancer by hr mas mr spectroscopy of Intact Tissue samples
Metabolites, 2017Co-Authors: Tonje Husby Haukaas, Guro F. Giskeødegård, Leslie R Euceda, Tone Frost BathenAbstract:Despite progress in early detection and therapeutic strategies, breast cancer remains the second leading cause of cancer-related death among women globally. Due to the heterogeneity and complexity of tumor biology, breast cancer patients with similar diagnosis might have different prognosis and response to treatment. Thus, deeper understanding of individual tumor properties is necessary. Cancer cells must be able to convert nutrients to biomass while maintaining energy production, which requires reprogramming of central metabolic processes in the cells. This phenomenon is increasingly recognized as a potential target for treatment, but also as a source for biomarkers that can be used for prognosis, risk stratification and therapy monitoring. Magnetic resonance (MR) metabolomics is a widely used approach in translational research, aiming to identify clinically relevant metabolic biomarkers or generate novel understanding of the molecular biology in tumors. Ex vivo proton high-resolution magic angle spinning (HR MAS) MR spectroscopy is widely used to study central metabolic processes in a non-destructive manner. Here we review the current status for HR MAS MR spectroscopy findings in breast cancer in relation to glucose, amino acid and choline metabolism.
-
High-resolution magic-angle-spinning NMR spectroscopy of Intact Tissue
Methods in Molecular Biology, 2015Co-Authors: Guro F. Giskeødegård, Maria D. Cao, Tone Frost BathenAbstract:High-resolution magic-angle-spinning (HR-MAS) NMR spectroscopy is a nondestructive technique that is used to obtain the metabolite profile of a Tissue sample. This method requires minimal sample preparation. However, it is important to handle the sample with care and keep it frozen during preparation to minimize degradation. Here, we describe a typical protocol for HR-MAS analysis of Intact Tissue. We also include examples of typical pulse sequence programs and quantification methods that are used today.
-
magnetic resonance metabolomics of Intact Tissue a biotechnological tool in cancer diagnostics and treatment evaluation
Cancer Research, 2010Co-Authors: Tone Frost Bathen, Beathe Sitter, Torill Eidhammer Sjobakk, Maybritt Tessem, Ingrid S GribbestadAbstract:Personalized medicine is increasingly important in cancer treatment for its role in staging and its potential to improve stratification of patients. Different types of molecules, genes, proteins, and metabolites are being extensively explored as potential biomarkers. This review discusses the major findings and potential of Tissue metabolites determined by high-resolution magic angle spinning magnetic resonance spectroscopy for cancer detection, characterization, and treatment monitoring.