Ability Of Nuclear Magnetic Resonance Research Articles

Role of NMR in High Ordered Structure Characterization of Monoclonal Antibodies.

Obtaining high ordered structure (HOS) information is of importance to guarantee the efficacy and safety of monoclonal antibodies (mAbs) in clinical application. Assessment of HOS should ideally be performed in a non-invasive manner under their formulated storage conditions, as any perturbation can introduce unexpected detritions. However, most of the currently available techniques only indirectly report HOS of mAbs and/or require a certain condition to conduct the analyses. Besides, the flexible multidomain architecture of mAbs has hampered atomic-resolution structural analyses using X-ray crystallography and cryo-electron microscopy. In contrast, the ability of nuclear magnetic resonance (NMR) spectroscopy to structurally analyze biomolecules in various conditions in a non-invasive and quantitative manner is suitable to meet the needs. However, the application of NMR to mAbs is not straightforward due to the high molecular weight of the system. In this review, we will discuss how NMR techniques have been applied to HOS analysis of mAbs, along with the recent advances of the novel 15N direct detection NMR strategy that allows for obtaining the structural fingerprint of mAbs at lower temperatures under multiple formulation conditions. The potential application of these NMR strategies will benefit next-generation mAbs, such as antibody-drug conjugates and bispecific antibodies.

Characterization of Brain Metabolism by Nuclear Magnetic Resonance.

The noninvasive, quantitative ability of nuclear magnetic resonance (NMR) spectroscopy to characterize small molecule metabolites has long been recognized as a major strength of its application in biology. Numerous techniques exist for characterizing metabolism in living, excised, or extracted tissue, with a particular focus on 1 H-based methods due to the high sensitivity and natural abundance of protons. With the increasing use of high magnetic fields, the utility of in vivo 1 H magnetic resonance spectroscopy (MRS) has markedly improved for measuring specific metabolite concentrations in biological tissues. Higher fields, coupled with recent developments in hyperpolarization, also enable techniques for complimenting 1 H measurements with spectroscopy of other nuclei, such as 31 P and 13 C, and for combining measurements of metabolite pools with metabolic flux measurements. We compare ex vivo and in vivo methods for studying metabolism in the brain using NMR and highlight insights gained through using higher magnetic fields, the advent of dissolution dynamic nuclear polarization, and combining in vivo MRS and ex vivo NMR approaches.

Analysis of salivary phenotypes of generalized aggressive and chronic periodontitis through nuclear magnetic resonance-based metabolomics.

Recent findings about the differential gene expression signature of periodontal lesions have raised the hypothesis of distinctive biological phenotypes expressed by generalized chronic periodontitis (GCP) and generalized aggressive periodontitis (GAgP) patients. Therefore, this cross-sectional investigation was planned, primarily, to determine the ability of nuclear magnetic resonance (NMR) spectroscopic analysis of unstimulated whole saliva to discriminate GCP and GAgP disease-specific metabolomic fingerprint and, secondarily, to assess potential metabolites discriminating periodontitis patients from periodontally healthy individuals (HI). NMR-metabolomics spectra were acquired from salivary samples of patients with a clinical diagnosis of GCP (n=33) or GAgP (n=28) and from HI (n=39). The clustering of HI, GCP, and GAgP patients was achieved by using a combination of the Principal Component Analysis and Canonical Correlation Analysis on the NMR profiles. These analyses revealed a significant predictive accuracy discriminating HI from GCP, and discriminating HI from GAgP patients (both 81%). In contrast, the GAgP and GCP saliva samples seem to belong to the same metabolic space (60% predictive accuracy). Significantly lower levels (P<0.05) of pyruvate, N-acetyl groups and lactate and higher levels (P<0.05) of proline, phenylalanine, and tyrosine were found in GCP and GAgP patients compared with HI. Within the limitations of this study, CGP and GAgP metabolomic profiles were not unequivocally discriminated through a NMR-based spectroscopic analysis of saliva.

Assessing the Ability of Spectroscopic Methods to Determine the Difference in the Folding Propensities of Highly Similar β-Hairpins.

We have evaluated the ability of nuclear magnetic resonance (NMR) and circular dichroism (CD) spectroscopies to describe the difference in the folding propensities of two structurally highly similar cyclic β-hairpins, comparing the outcome to that of molecular dynamics simulations. NAMFIS-type NMR ensemble analysis and CD spectroscopy were observed to accurately describe the consequence of altering a single interaction site, whereas a single-site 13C NMR chemical shift melting curve-based technique was not.

1H NMR To Explore the Metabolome of Exhaled Breath Condensate in α1-Antitrypsin Deficient Patients: A Pilot Study.

The metabolomic analysis of exhaled breath condensate (EBC) may provide insights on both the pathology of pulmonary disorders and the response to therapy. This pilot study describes the ability of nuclear magnetic resonance (NMR)-based metabolomics to discriminate α1-antitrypsin deficient (AATD)-patients, who were diagnosed with moderate to severe emphysema, from healthy individuals. Comparative analysis of samples from these two homogeneous cohorts of individuals resulted in the generation of NMR profiles that were different from both a qualitative and a quantitative point-of-view. Among the identified metabolites that separated patients from controls, acetoin, propionate, acetate, and propane-1,2 diol were those presenting the biggest difference. Unambiguous confirmation that the two groups could be completely differentiated on the basis of their metabolite content came from the application of univariate and multivariate statistical analysis (principal component analysis, partial least squares discriminant analysis (PLS-DA), and orthogonal PLS-DA). MetaboAnalyst 3.0 platform, used to define a relationship among metabolites, allowed us to observe that pyruvate metabolism is the most-involved pathway, most of metabolites being originated from pyruvate. These preliminary data suggest that NMR, with its ability to differentiate the metabolic fingerprint of EBC of AATD patients from that of healthy controls, has a potential "clinical applicability" in this area.

Perspectives on NMR in drug discovery: a technique comes of age

In the past decade, the potential of harnessing the ability of nuclear magnetic resonance (NMR) spectroscopy to monitor intermolecular interactions as a tool for drug discovery has been increasingly appreciated in academia and industry. In this Perspective, we highlight some of the major applications of NMR in drug discovery, focusing on hit and lead generation, and provide a critical analysis of its current and potential utility.

Nonequilibrium cation distribution in nanocrystalline MgAl 2O 4 spinel studied by 27Al magic-angle spinning NMR

Nanocrystalline magnesium aluminate (MgAl 2O 4) powders were prepared by high-energy milling of the bulk material. Due to the ability of nuclear magnetic resonance (NMR) spectroscopy to discriminate between probe nuclei on inequivalent crystallographic sites, valuable insight into the mechanically induced evolution of a local cation disorder in MgAl 2O 4 can be obtained. It, thus, was revealed for the first time that the mechanical treatment of MgAl 2O 4 tends to randomize ions over the cation spinel sublattices. Quantitative microstructural information on the nonequilibrium cation distribution provided by 27Al MAS-NMR is complemented by XRD and TEM investigations revealing the nanoscale nature of the milled material. The cation inversion parameter of the nanosized MgAl 2O 4 is compared with that of the bulk material at non-ambient conditions.

Non-Invasive monitoring of a bioartificial pancreas in vitro and in vivo.

Monitoring biochemical processes relevant to the function, survival, and longevity of tissue-engineered pancreatic constructs is important for the development of an optimum construct design as well as patient care management after implantation. In this report we demonstrate the ability of nuclear magnetic resonance (NMR) techniques to monitor aspects of intracellular metabolism, overall morphology, and distribution of a microencapsulation based bioartificial pancreas in vitro and in vivo.

Distinguishing viable from infarcted myocardium after experimental ischemia and reperfusion by using nuclear magnetic resonance imaging

Early reperfusion has the potential for salvaging ischemic myocardium at risk for infarction. To test the ability of nuclear magnetic resonance (NMR) imaging to differentiate between stunned and infarcted myocardium early after reperfusion, 16 mongrel dogs underwent transient occlusion of the left anterior descending artery or a diagonal branch for 30, 60 or 180 min followed by reperfusion. To identify the area at risk for infarction and to assess the extent of hypoperfusion and reperfusion, two-dimensional and contrast echocardiography were performed at baseline study, during coronary occlusion and at three separate times during reperfusion (before NMR imaging, immediately after NMR imaging and 12 to 14 h later). Wall thickening in the control and ischemic zones and the circumferential extent of abnormal wall motion were analyzed at each time point using short-axis echocardiograms. Nuclear magnetic resonance imaging at 1.5 tesla was performed 2 to 3.5 h (mean 2.7 +/- 0.5) after reperfusion. Short-axis, multislice spin-echo images (TE 26 and TE 60) were obtained. Signal intensity was measured in the control and ischemic areas and expressed as a percent difference compared with normal myocardium. All dogs demonstrated a significant decrease in wall thickening and abnormal wall motion before and after NMR imaging. Seven of the eight dogs with infarction had an area of increased signal intensity on TE 60 images. The mean percent difference in signal intensity compared with adjacent normal myocardium was 127 +/- 68% (p = 0.002). None of the eight dogs without infarction had a visually apparent change in signal intensity on TE 60 images (mean percent difference versus control area 13 +/- 11%), despite regional systolic dysfunction documented by echocardiography at the time of imaging. The area of increased signal intensity correlated with infarct size (r = 0.69), although overestimation by NMR imaging occurred. The area of increased signal intensity did not correlate with the extent of echocardiographic contrast defect during coronary occlusion (risk area). This study demonstrates that NMR imaging can be applied early after coronary reperfusion to assess the potential for recovery of dysfunctional myocardium. In addition, by using a TE 60 multislice spin-echo imaging sequence at 1.5 tesla, quantification of the extent of infarction also may be possible.

Determination of left ventricular volumes and ejection fraction by nuclear magnetic resonance imaging

To determine the ability of nuclear magnetic resonance (NMR) imaging to assess left ventricular (LV) volumes and ejection fraction (EF), we studied 24 patients within 48 hours of single-plane LV angiography. In all patients, a transverse, single-plane NMR acquisition technique was employed with LV end-diastolic (ED) and end-systolic (ES) volumes (V) calculated by a modified area-length algorithm. In nine patients, a multialice acquisition technique was employed with LVEDV and LVESV calculated by a Simpson's rule algorithm. NMR-determined LVV and EF correlated reasonably well with angiographic values (LVEDV: r = 0.75; LVE8V: r = 0.90; and LVEF: r = 0.76). The singie-plane NMR technique significantly underestimated LVEDV ( p < 0.01), whereas no significant difference was demonstrated for LVESV. As a result, angiographic LVEF was significantly underestimated ( p < 0.05). This underestimation is likely related to off-axis imaging and to the geometric constraints of a single-plane algorithm. In comparing multislice NMR to angiographic data, no significant difference was demonstrated for LVEDV, LVESV, or LVEF. Thus, quantitation of LVV and EF with NMR is feasible, and comparison to angiographic volumes is similar to results reported from other noninvasive imaging modalities. Improvement in current acquisition techniques and software should result in further quantitative potential.

Nuclear magnetic resonance (NMR) tomographic imaging for popliteal cysts in rheumatoid arthritis.

The ability of nuclear magnetic resonance (NMR) tomographic imaging to show a change in proton spin-lattice relaxation time (T1 value) in the joints of patients with rheumatoid arthritis before and after treatment with intra-articular steroid has been assessed. Six patients with seropositive rheumatoid arthritis and clinical evidence of a popliteal cyst were examined by both NMR tomography and arthrography. In all cases the presence of active rheumatoid arthritis was shown by an increase in the T1 values of the synovium of the joints. After arthrography a consistent but small rise in T1 value was noted which fell to below the initial reading after treatment by intra-articular injection of an anti-inflammatory agent. In all cases the presence of the popliteal cyst was clearly shown by both NMR tomography and arthrography. The findings indicate that NMR tomography provides a sensitive method for the demonstration of inflammatory joint disease, popliteal cysts, and possibly for monitoring response to therapy.

Nuclear magnetic resonance imaging of the adrenal gland: A preliminary report

Nuclear magnetic resonance (NMR) imaging characteristics of the normal and abnormal adrenal gland were evaluated and compared with findings on computed tomography (CT). Forty-two patients were examined: 36 had normal adrenal glands and 6 had adrenal disease (3 metastatic lesions, 1 pheochromocytoma, and 2 cortical hyperplasia). NMR clearly showed all 42 left adrenals (100%) and 36 right adrenals (86%). In some patients, it appeared to differentiate the adrenal cortex from the medulla. The ability of NMR to detect adrenal disease was similar to that of CT in 6 cases examined. CT demonstrated superior spatial resolution in most cases, but NMR provided superior soft-tissue contrast. Since NMR does not involve ionizing radiation and provides excellent soft-tissue differentiation without contrast material, it has advantages over CT and appears to be a promising modality for imaging of the adrenal gland.

Nuclear magnetic resonance imaging of the mediastinum and hili: Early impressions of its efficacy

Nuclear magnetic resonance (NMR) scans of the mediastinum and/or hili were obtained in 22 of 25 patients selected on the basis of an abnormal CT scan. All patients had proven disease; 19 malignant and four benign processes were studied successfully. The high contrast resolution of NMR in the mediastinum allowed clear definition of disease in all cases. In six, NMR showed a greater extent of disease than CT. The ability of NMR to perform sagittal and coronal images also aided in disease analysis. In this preliminary study, NMR proved to be as useful as CT, or more so, in the evaluation of malignant disease of the hili and mediastinum.

Nuclear Magnetic Resonance Studies on Human Breast Dysplasias and Neoplasms&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;

The ability of nuclear magnetic resonance (NMR) spectroscopy to distinguish normal, diseased non-neoplastic, and neoplastic human breast tissues was investigated with T1 and T2 relaxation times used. The results indicated that NMR relaxation times could distinguish between the mean values of breast neoplasms and other diseased or normal tissues, with P values less than 0.001. Given a single sample, the probability of classifying it nonneoplastic or carcinoma could be accomplished with 85% confidence. For human breast tissues, the relaxation time T2 may be more discriminating that T1. These results support the view that the use of NMR spectroscopy in cancer detection may be of significant value and warrants considerable more interest and effort to determine the beneficial applications and limits of this technology.