Nuclear magnetic resonance studies of the active site of carboxypeptidase A.
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Carboxypeptidases↗
Biomedical subjects
G Navon
Publications and source records attributed to G Navon.
The action of atomic hydrogen on trypsin in aqueous solution.
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Chemical Phenomena↗
Relaxation times and concentrations of 7Li in the brain of patients receiving lithium therapy.
The present study describes a protocol for the determination of in vivo absolute molar concentrations of Li+ in the human brain using a double tuned 1H/7Li surface coil. The protocol follows the method of Thulborn and Ackerman [J. Mag. Reson. 55, 357-371 (1983)] where the ratio of the signal intensities of 7Li and 1H in the brain is compared to the same ratio in a phantom containing known concentrations of Li+. The 7Li T1 values in the brains of five patients receiving lithium therapy were measured. The average result was T1 = 3.5 +/- 0.25 s. The phantom solution was adjusted to have this T1 value. The protocol was applied for eight bipolar patients receiving lithium therapy. The average ratio of brain to serum lithium molar concentration was found to be 0.59 +/- 0.12.
Adult↗
HGF/SF activates glycolysis and oxidative phosphorylation in DA3 murine mammary cancer cells.
Hepatocyte growth factor/scatter factor (HGF/SF) is a paracrine growth factor which increases cellular motility and has also been implicated in tumor development and progression and in angiogenesis. Little is known about the metabolic alteration induced in cells following Met-HGF/SF signal transduction. The hypothesis that HGF/SF alters the energy metabolism of cancer cells was investigated in perfused DA3 murine mammary cancer cells by nuclear magnetic resonance (NMR) spectroscopy, oxygen and glucose consumption assays and confocal laser scanning microscopy (CLSM). 31P NMR demonstrated that HGF/SF induced remarkable alterations in phospholipid metabolites, and enhanced the rate of glucose phosphorylation (P < .05). 13C NMR measurements, using [13C1]-glucose-enriched medium, showed that HGS/SF reduced the steady state levels of glucose and elevated those of lactate (P < .05). In addition, HGF/SF treatment increased oxygen consumption from 0.58+/-0.02 to 0.71+/-0.03 micromol/hour per milligram protein (P < .05). However, it decreased CO2 levels, and attenuated pH decrease. The mechanisms of these unexpected effects were delineated by CLSM, using NAD(P)H fluorescence measurements, which showed that HGF/SF increased the oxidation of the mitochondrial NAD system. We propose that concomitant with induction of ruffling, HGF/SF enhances both the glycolytic and oxidative phosphorylation pathways of energy production.
Adenocarcinoma↗
A decoupled coil detector array for fast image acquisition in magnetic resonance imaging.
A method for magnetic resonance imaging (MRI) is investigated here, whereby an object is put under a homogeneous magnetic field, and the image is obtained by applying inverse source procedures to the data collected in an array of coil detectors surrounding the object. The induced current in each coil due to the precession of the magnetic dipole in each voxel depends on the characteristics of both the magnetic dipole frequency and strength, together with its distance from the coil, the coil direction in space, and the electrical properties of the coils. By calculating the induced current signals over an array of coil detectors, a relationship is established between the set of signals and the structure of the body under investigation. The linear relation can then be represented in matrix notation, and inversion of this matrix will produce an image of the body. Important problems which must be considered in the proposed method are signal-to-noise ratio (SNR) and coupling between adjacent coils. Solutions to these problems will provide a new method for obtaining an instantaneous image by NMR, with no need for gradient switching for encoding. A general algorithm for decoupling of the coils is presented and fast sampling of the signal, instead of filtering, is used in order to reduce both noise and numerical roundoff errors at the same time. Sensitivity considerations are made with respect to the number of coils that is required and its connection with coil radius and SNR. A computer simulation demonstrates the feasibility of this new modality. Based on the solutions presented here for the problems involved in the use of a large number of coils for a simultaneous recording of the signal, an improved method of multicoil recording is suggested, whereby it is combined with the conventional zeugmatographic method with read and phase gradients, to result in a novel method of magnetic resonance imaging. In the combined method, there are no phase-encoding gradients. Only a single slice-selecting gradient, to be followed by a single read-gradient. Instead of phase-encoding gradients, use is made of an equivalent number of coils. The number of coils now is reduced significantly. This method suggests a single slice image taken within a single echo time, and where a 128 x 128 resolution is possible with only 128 coils. The applicability of the method is based on a successful decoupling procedure for the detectors (coils and cables) and the availability of highly accurate, high-gain, low-noise amplifiers with a broad dynamic range.
Computer Simulation↗
NMR studies of recombinant active site peptides of the nicotinic acetylcholine receptor.
Interactions of ligands with recombinant cholinergic binding sites have been monitored by NMR. Monitoring the selective T1 relaxation of the protons of acetylcholine, nicotine, d-tubocurarine, and gallamine reveals specific binding to peptide constructs containing the alpha 183-204 or shorter sequences of the nicotinic acetylcholine receptor of Torpedo, Human, Chicken, Xenopus, Mouse, Calf, and Drosophila. The trend of the KD values of the different ligands shows that the binding of the low molecular weight agonists and antagonists is very weak to the Drosophila sequence which is different from the vertebrate sequences in the N and C terminals. Within the vertebrates, the antagonists d-tubocurarine and gallamine display a KD trend different from that of acetylcholine and alpha-bungarotoxin. Specificity of binding is proven by the fact that atropine, a muscarinic inhibitor, binds non-specifically. Temperature dependence indicates a fast exchange limit (T1 bound greater than tau bound) for gallamine bound to the Torpedo alpha 184-200 sequence. This limit should apply also for the other ligands which have weaker binding constants.
Algorithms↗