bluuebunny/crossref_metadata_2025_split huggingface dataset:
The metabolism of lactate
Authors: Veech Richard L. 
Published: March 2007

AbstractLactate contents of tissues can vary during normal physiological conditions in mammals from 0.5 to over 5 mM, and higher in pathological states, suitable for measurement by NMR. Lactate itself is a dead‐end metabolite, metabolized only by lactate dehydrogenase. The extent and direction of that reaction is determined by the free [NAD+]/[NADH][H+] ratio of cytoplasm with which lactate and pyruvate are in near‐equilibrium. Pyruvate is a crossroads of most of the major degradative and synthetic pathways, but present in about one‐tenth the amount of lactate. Information on the content of both lactate and its redox partner pyruvate is likely to provide more information on the metabolic state of tissue than are measurements of lactate alone.
Biochemical considerations in 1H spectroscopy. Glutamate and glutamine; Myo‐inositol and related metabolites
Authors: Ross Brian D. 
Published: March 2007

AbstractGlutamate and glutamine, which can be clearly identified and, in part, quantified in proton spectra of the brain, play important roles in normal and pathological biochemistry. Pathways of glutamate metabolism include transamination, dehydrogenation, deamination and decarboxylation (to GABA). Glutamine is notable in hepatic encephalopathy, but is also a significant metabolic fuel in several other organs and tissues, including neoplasms. Myo‐inositol is a 6‐carbon alcohol which acquires new interest from its detection and quantitation in 1H spectra. Its role, apart from a biochemical relationship to messenger‐inositol polyphosphates, is unclear.
Multiple quantum NMR spectroscopy methods for measuring the apparent self‐diffusion coefficient of In Vivo lactic acid
Authors: Sotak Christopher H. 
Published: March 2007

AbstractNuclear magnetic resonance spectroscopy methods are presented for measuring the apparent self‐diffusion coefficient of lactic acid in vivo. These techniques incorporate diffusion‐sensitive gradients into multiple quantum NMR pulse sequences that are employed for spectral editing. Both diffusion‐sensitive zero quantum (ZQ) and double quantum (DQ) spectral editing techniques have been developed and the DQ method has been used to measure the apparent self‐diffusion coefficient of in vivo lactic acid in H‐MESO‐1 human tumor xenografts subcutaneously implanted in athymic mice.
Proton editing and imaging of lactate
Authors: Hurd Ralph E. , Freeman Dominique 
Published: March 2007

AbstractHighly specific NMR assays for the detection, quantitation and imaging of lactate in vivo are described. Applications in animals include tumor monitoring, the determination of hypoxic cell distribution and the demonstration of the efficacy of tumor‐sensitizers. The methods (GE‐DQCOSY and GE‐HMQC) may be particularly useful in heteronuclear NMR in vivo.
Quantification of glutamate, glutamine, and other metabolites in In Vivo proton NMR spectroscopy
Authors: Bovée W. M. M. J. 
Published: March 2007

AbstractA reliable quantification of in vivo 1H MRS spectra is hampered by extensive line overlap, by intensity distortions due to the water suppressing pulse sequence and complex modulation patterns of J‐coupled spins, and by deviations between the experimental and model lineshapes in computer fitting programs. By correcting the experimental lineshape, using a suitable pulse sequence, and incorporating prior knowledge about the spin systems and the intensity distortions, a sufficient quantification is possible. If reliable. T2 values are available absolute concentrations can be determined.
Approaches to editing, assignment and interpretation of proton spectra
Authors: Gadian D. G. , Bates T. E. , Williams S. R. , Bell J. D. , Austin S. J. , Connelly A. 
Published: March 2007

AbstractClinical 1H spectroscopy of the brain is complemented by parallel analyses of biopsy specimens and by studies of animal models of disease. 1H spectroscopy has been carried out on perchloric acid extracts of biopsy specimens from patients with intracranial tumours. The data suggest that clinical spectroscopy may be useful in the identification and grading of these tumours. In addition, the spectra from extracts derived from normal white matter add weight to the possibility that acetyl‐containing compounds other than N‐acetylaspartate may make a significant contribution to the signal at 2.0 ppm in vivo. Edited 1H spectra of brain metabolites in rats with acute liver failure demonstrate an elevation of glutamine and of lactate, suggesting a role for 1H spectroscopy in clinical investigations of metabolic encephalopathies. However, the observation and resolution of signals from glutamate and glutamine is more difficult at the lower fields that are available for clinical spectroscopy. Finally, some studies of patients with inborn errors of metabolism are described. It is shown that in a disorder of oxidative metabolism, brain lactate can be detected without the need for complex spectral editing techniques. Investigations of the metabolic abnormalities associated with Canavan's disease have shed further light on a possible role for N‐acetylaspartate.
On the identification of cerebral metabolites in localized 1H NMR spectra of human brain In vivo
Authors: Michaelis Thomas , Merboldt Klaus‐Dietmar , Hänicke Wolfgang , Gyngell Michael L. , Bruhn Harald , Frahm Jens 
Published: March 2007

AbstractLocalized 1H NMR spectra of human brain in vivo are affected by signal overlap, strong spin‐spin coupling, and complex J modulation, and therefore differ considerably from those obtained at higher magnetic fields. This paper deals with the assignment of 1H NMR resonances of cerebral metabolites under the experimental conditions used for human investigations. Conventional 7.0‐T FID spectra and 2.0 T localized, short echo time STEAM spectra (TE = 20 ms) of aqueous metabolite solutions are compared to in vivo brain spectra of human volunteers and patients. In addition to singlet resonances from N‐acetyl aspartate (NAA), creatines, and cholines, short echo time STEAM spectra exhibit multiplets due to the NAA aspartyl group, glutamate, taurine, and myo‐inositol. Enhanced levels of cerebral glutamine are detected in patients with liver cirrhosis. For the first time elevated levels of brain glucose are observed in patients with diabetes mellitus.
What the clinician can learn from MR glutamine/glutamate assays
Authors: Chamuleau R. A. F. M. , Bosman D. K. , Bovée W. M. M. J. , Luyten P. R. , Den Hollander J. A. 
Published: March 2007

AbstractAt present in vivo NMR spectroscopic studies of brain glutamate and glutamine concentrations relative to encephalopathy have mainly been performed in hepatic encephalopathy (HE). In vivo proton NMR studies were performed in rats with hyperammonemia and acute HE due to acute liver ischemia as well as in rats with hyperammonemia due to either repeated urease i.p. injection or i.p. administration of methionine sulfoximine, a well known inhibitor of glutamine synthetase. In man, in vivo proton NMR is described in patients with chronic liver disease: cirrhosis of different etiology and associated with different degrees of HE. In the experimental models proton NMR spectroscopy of the cerebral cortex revealed an increase in glutamine concentration, a decrease in glutamate concentration and a decrease in phosphocholine compounds. In humans no clear distinction between cerebral cortex glutamate and glutamine concentration could be made by in vivo 1H NMR spectroscopy. However, the combined glutamate/glutamine peak increased in a way compatible with an increased cerebral cortex glutamine concentration during chronic HE. In the cirrhotic patients too a decrease in cerebral cortex phosphocholine compounds was observed, the explanation of which is unclear. Both the experimental work and the clinical observations support the hypothesis that impairment of the glutamate/glutamine cycle between astrocytes and neurons plays a role in the pathogenesis of hepatic encephalopathy.
Localized 1H NMR spectroscopy in patients with chronic hepatic encephalopathy. Analysis of changes in cerebral glutamine, choline and inositols
Authors: Kreis Roland , Farrow Neil , Ross Brian D. 
Published: March 2007

AbstractLocalized, short echo 1H magnetic resonance spectra from an area in the parietal cortex of three patients suffering from chronic hepatic encephalopathy are compared with equivalent spectra obtained from healthy control subjects. Three significant differences are found: elevated glutamine, decreased inositol, and decreased choline peak intensities. The elevation of cerebral glutamine concentration is expected as a consequence of the presumed chronic hyperammonemia in this disease. The finding of a 50% change in the inositol peak is physiologically unexpected and so far unaccounted for.Data acquisition and processing parameters are described in detail. To further define spectral abnormalities, which were readily detected in untransformed spectra, a simple data analysis scheme has been used that consists of post‐acquisition low‐frequency filtering, a lineshape transformation, and a difference technique to clarify spectral changes.
Time‐dependent effects of anesthetic agents on 31P NMR high‐energy phosphates in KHT and RIF‐1 fibrosarcomas
Authors: Fenton Bruce M. , Raubertas Richard F. , Sutherland Robert M. 
Published: March 2007

AbstractPrevious studies have reported significant radiobiological and hemodynamic effects associated with sodium pentobarbital (PB) anesthetization. The present work contrasts the effects of PB with azaperone‐ketamine (AZ) in RIF‐1 and KHT tumors while animal body core temperature is maintained at 37 °C. The primary aims were to evaluate both agents in terms of: (i) duration of anesthetic; (ii) effect on absolute levels of 31P NMR phosphocreatine (PCr) + β‐nucleoside triphosphate (β‐NTP)/inorganic phosphate (Pi) ratios; and (iii) effect on temporal variability of PCr+β‐NTP/Pi ratios. In terms of overall duration, AZ was the clear preference. Although the maintenance of 37 °C core temperature significantly reduced overall durations for both anesthetics, AZ animals invariably remained immobile for a minimum of 80 min. For PB, durations were highly unpredictable. With AZ, mean PCr + β‐NTP/Pi ratios were constant over the entire 80 min period for both lines. With PB, PCr + β‐NTP/Pi ratios were lower in relation to AZ for KHT at select timepoints, but highly variable among RIF‐1 tumours. Since ratios under PB varied substantially with time for RIF‐1 lines, measurements taken with PB are clearly not representative of the control state. Furthermore, in light of the consistent and reproducible results obtained with AZ, this anesthetic is considered a marked improvement over PB for animal studies of this nature.
Proton nuclear magnetic resonance spectroscopy measurements of methylene and methyl line widths in plasma: Significant variations with extent of breast cancer, duration of pregnancy and aging
Authors: Engan Terje , Krane Jostein , Kvinnsland Stener 
Published: March 2007

AbstractThe composite methylene (chemical shift range 1.2‐1.4 ppm) and methyl (0.8‐0.9 ppm) resonances of the 1H NMR spectrum were analyzed in plasma samples from breast tumor patients, pregnant women, and healthy subjects. Using a 500 MHz NMR instrument operating at 25 °C, the peaks were analyzed for line width at half height and then averaged. A statistically significant difference (p<0.001) was found between the average (mean ±SD) line width in the plasma samples from the 30 patients with metastatic breast cancer (34.1 ±5.0 Hz) and the controls matched for age and sex (38.7 ±4.4 Hz). In the 16 patients with localized breast cancer and the 16 with regional spread, the average line width was not different from that of matched controls. In 21 patients with benign tumor in the breast, the average line width was not different from that of matched controls. A difference in the average line width was found between 31 pregnant women in the third trimester (32.5±3.4 Hz) and their controls matched for age and sex (42.7±4.6 Hz) (p<0.001). The average line width was lower in the late (31.5±3.3) than in the early (34.5±2.5 Hz) part of the third trimester (p = 0.022). In 54 healthy male and 130 healthy female controls, line widths declined gradually with increasing age by decades, except in the fifth decade for the men and the sixth decade for the women. The observations are consistent with an association between ‘stage’ in a most general sense and the apparent NMR lipid line widths, probably accounted for by a variation in plasma lipids.
Non‐invasive 1H NMR spectroscopy of the rat brain In Vivo using a short echo time STEAM localization sequence
Authors: Gyngell M. L. , Ellermann J. , Michaelis T. , Hänicke W. , Merboldt K. D. , Bruhn H. , Frahm J. 
Published: March 2007

AbstractFully localized proton NMR spectra were obtained from the brains of normal anaesthetized rats in vivo using stimulated echo (STEAM) spectroscopy sequences. Investigations were carried out at 2.35 T using a 40 cm bore magnet equipped with an actively shielded gradient system. Localized shimming resulted in water proton linewidths of 6.5‐7.8 Hz permitting excellent water suppression. Thus, high‐quality proton NMR spectra (TE = 20 ms) were acquired within measuring times of 1.5‐6.4 min from 64 to 125 μL volumes‐of‐interest. The spectra show metabolite resonances due to N aspartate, glutamate, creatine and phosphocreatine, cholines, taurine and inositols. The assignments of strongly spin‐coupled resonances were confirmed by comparison with spectra from model solutions obtained under identical experimental conditions to those used in vivo. Tl relaxation times as well as relative metabolite concentrations were evaluated from spectra obtained for repetition times ranging from 900 to 6000 ms. Sequential acquisitions of 1.5 min spectra before, during and after killing the animals exhibited a rapid accumulation of lactate, but did not reveal significant changes in other metabolite levels for several hours post mortem.
Estimating the ATP cost of force production in the human gastrocnemius/soleus muscle group using 31P MRS and 1H MRI
Authors: Boska Michael 
Published: March 2007

AbstractNet ATP production rates in exercising human muscle were calculated from 31P MRS kinetic data collected with 1‐8 s time resolution. During the exercise, the muscle output was measured using a force transducer. Muscle output (force/unit volume) is then divided by the calculated net ATP used to estimate the ATP cost of force production. These measurements have been performed using an exercise protocol of isometric maximum voluntary contraction of the gastrocnemius/soleus muscle group. Results show that by the end of 30 s of exercise, total ATP production and ATP cost of force production had stabilized and remained constant (within the measurement errors) until the end of the 2‐min period. The results also demonstrate that either the ATP cost of force production in the human gastrocnemius/soleus is lower in the first second than at any other time in the 2‐min window which was investigated, or that the ATP production is being underestimated at the later time points. These data on ATP production rates, and the data relating to ATP cost of force production in muscle will aid in understanding the causes of muscle failure as well as the progression and treatment of muscle disease.
1H NMR spectroscopic imaging of the monkey brain using binomial water suppression in a stimulated‐echo sequence
Authors: Richards Todd L. 
Published: March 2007

AbstractA new proton, two‐dimensional pulse sequence for 1H NMR spectroscopic imaging (chemical shift imaging) was tested in phantoms and in the monkey brain. The pulse sequence consisted of one binomial chemically selective pulse and two spatially selective pulses in the stimulated‐echo sequence. The point‐spread function (which is influenced by k‐space filtering and the number of phase‐encoded steps) of a 1 mm source phantom was measured using a 16 X 16 spatial matrix and was found to have a FWHM of 10 mm (100 mm field of view) with very little rippling outside the main lobe. The binomial excitation profile was measured in order to correct the NMR intensity for the variable flip angles. Spectroscopic images were measured in the monkey brain with a 15 mm slice thickness and a 16 X 16 spatial matrix. Proton spectra derived from the brain contained sharp resonances of choline, creatine and N‐acetyl aspartate with minimal lipid contamination. Proton spectra derived from the subcutaneous fat and adipose tissue behind the eyes contained large lipid resonances.
A comprehensive approach to the analysis and interpretation of the resonances of spins 3/2 from living systems
Authors: Rooney William D. , Springer Charles S. 
Published: March 2007

AbstractAn extensive protocol for the study of tissue resonances of spin 3/2 nuclei is described. The roles of the most relevant multiple pulse experiments are indicated. Their theory is organized in terms of irreducible tensor operators and the pulse and quadrupolar relaxation transfer functions which relate them for a type c spectrum. A systematic approach to the interpretation of the temperature and/or magnetic field dependences of all six of the relaxation rate constants of the resonance of a single population of isolated spins in fast exchange, and giving rise to a type c spectrum, is presented. An experimental calibration and an application of this protocol are presented in an accompanying paper. The comprehensive method we describe has a number of practical benefits in the interpretation of the physiological spectra obtained from conventional one pulse experiments. A consideration of the appropriate transverse relaxation transfer function leads to an analytical expression for the heretofore empirical NMR visibility factor. This includes factors which account for relaxation during the receiver ‘dead’ time and relaxation during the pulse itself. Also, consideration of realistic transverse relaxation times likely to be observed in tissue leads to a reasonable strategy for the quantitative resolution and integration of in vivo spectra obtained in the presence of hyperfine shift reagents.
The molecular environment of intracellular sodium: 23Na NMR relaxation
Authors: Rooney William D. , Springer Charles S. 
Published: March 2007

AbstractThe comprehensive approach described in the accompanying paper is illustrated here with the 23Na signal of a concentrated solution of bovine serum albumin (BSA) in saline and the intracellular (Nai) 23Na resonance of a dense suspension of Na+ ‐loaded yeast cells. We use frequency shift reagents to discriminate the latter from the extracellular resonance. We find that the Nai signal corresponds to that of an effective single population of Na+ ions exhibiting a single type c spectrum. This is true despite the fact that the yeast protoplasm is too large and too compartmentalized for a given Na+ ion to sample its entirety on the relevant NMR timescale. Our results show clearly that, in addition to the decay of transverse magnetization, the recovery of longitudinal magnetization is biexponential. This is required for a type c spectrum but has not often been detected. The temperature dependence of the relaxation rate constants of the Nai resonance is not consistent with either a simple Debye process or a discrete exchange mechanism connecting two sites in the fast limit. We have fitted the data using an asymmetric continuous distribution of correlation times for the fluctuations of electric field gradients sensed by the Nai nuclei. The analogous distribution function for the Na+ in a 44% (w/w) BSA solution is quite similar to that of the Nai at the same temperature. This suggests that while the macromolecular environment of the Nai ions is quite congested, it is also isotropic on quite a small spatial scale. Also, one can use the correlation time distribution function, obtained from fitting the relaxation data, to calculate a relaxometry curve. This is useful because experimental 23Na relaxometry is difficult. The calculated curve may be a reasonable model for the mostly extracellular 23Na resonance encountered in vivo.
Characterization of a microcarrier cell culture system for 23Na MR spectroscopy studies
Authors: Shedd Suzanne F. , Spicer Leonard D. 
Published: March 2007

AbstractA MR spectroscopy method is described for the simultaneous discrimination and observation of sodium from the three compartments created by an intact cell monolayer. Results are reported for Madin Darby Canine Kidney (MDCK) cells, an epithelial‐like continuous cell line, cultured on Cytodex 1 microcarrier beads and perfused with medium containing 6 mM dysprosium (III) tripolyphosphate [Dy(TPP)72] as shift reagent. The sodium spectrum shows three resonances which are assigned to the shifted intrabead (basolateral) and extrabead (apical) pools and the unshifted intracellular pool. Ouabain inhibition of the Na+ ‐K+ ‐ATPase cellular pump mechanism was used to demonstrate the sensitivity of the method for monitoring intracellular sodium. The supported MDCK cells in this system remained viable after exposure for 5 h to medium containing Dy(TPP)72 at a concentration of 6 mM, as determined by trypan blue dye exclusion and by comparison of the log growth rate and ability to form domes in subsequent generations of exposed cells vs unexposed controls.
Metabolite images of the human arm: Changes in spatial and temporal distribution of high energy phosphates during exercise
Authors: Nelson Sarah J. , Taylor June S. , Vigneron Daniel B. , Murphy‐Boesch Joseph , Brown Truman R. 
Published: March 2007

AbstractLocalized variations in metabolites in resting and exercising skeletal muscle have been studied using Chemical Shift Imaging (CSI) techniques to obtain 2‐D arrays of 31P NMR spectra from a slice through the human forearm. The excitation profile of the coil resulted in a slice thickness of ca 80 mm and the planar resolution of the CSI data corresponded to either 7, 10 or 14 mm. The metabolite information was represented both as 2‐D arrays of spectra and by constructing images of the spatial distribution of different metabolites. Correlation with the anatomy was clearly visualized by overlaying the metabolite images on the appropriate region of the corresponding proton images. At rest, significant variations in the intensity of Pi, phosphocreatine (PCr) and ATP were observed in different regions of the arm. Our planar spatial and temporal (1‐9 min) resolution was also sufficient to follow changes in Pi, PCr and pH in response to exercise. These changes were restricted to the exercising muscle and demonstrated heterogeneity both in the kinetics and magnitude of response between different muscles.
Detection of differential sensitivity to 5‐fluorouracil in ehrlich ascites tumour cells by 19F NMR spectroscopy
Authors: McSheehy P. M. J. , Maxwell R. J. , Griffiths J. R. 
Published: March 2007

AbstractQuantitative analysis of extracts from two Ehrlich ascites tumour cell lines (Lettre cells) by 19F NMR in vitro demonstrated that one Lettre cell line (designated LLM) metabolized 30‐50% less 5‐fluorouracil to 5‐fluoronucleotides when compared to the other cell line (designated LHM). HPLC analysis of these cellular extracts showed a significant decrease in the concentration of the cytotoxic nucleotide 5‐fluorouridine triphos‐phate in LLM cells compared to LHM cells. No major differences could be observed in the 31P and 1H NMR spectra of the two cell lines. Growth inhibition studies in vitro demonstrated that LLM cells were less sensitive to 5‐fluorouracil than LHM cells. These results are consistent with the hypothesis that 19F NMR visible levels of 5‐fluoronucleotides can predict the cytotoxicity of the anti‐cancer drug 5‐fluorouracil.