bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biotransformation of 2‐fluoroaniline in rats studied by In Vivo19F NMR
Authors: Vervoort J. , Rietjens I. M. C. M. , Moonen C. T. W. , Von Kienlin M. , Despres D. 
Published: March 2007

AbstractThe present study describes results from an in vivo 19F NMR study on rats exposed to the xenobiotic compound 2‐fluoroaniline. Qualitative pharmacokinetics and the biotransformation of 2‐fluoroaniline were studied after exposure to 50 mg/kg body wt 2‐fluoroaniline. Accumulation and elimination of the parent compound in and from the liver of exposed animals were readily observed. Metabolites formed in the liver were shown to be efficiently excreted from the liver, as the amount of metabolites in this organ was always <10% of the maximum amount of the parent compound observed. In the bladder, rapid accumulation of 2‐fluoroaniline‐derived metabolites was detected. The metabolite pattern was shown to change in time, with the parent compound being dominantly present during the first hours of exposure. N‐acetylated products (4‐acetamido‐3‐fluorophenyl sulphate and 4‐acetamido‐3‐fluorophenyl glucuronide) were observed to accumulate more slowly in the bladder than the non‐acetylated products (4‐amino‐3‐fluorophenyl sulphate and 4‐amino‐3‐fluorophenyl glucuronide). Urine metabolite patterns obtained from the bladder in vivo were compared to those obtained during metabolic cage experiments.
The effect of intra‐tumour heterogeneity on the distribution of phosphorus‐containing metabolites within human breast tumours: An In Vitro study using 31P NMR spectroscopy
Authors: Smith T. A. D. , Glaholm J. , Leach M. O. , Machin L. , McCready V. R. 
Published: March 2007

AbstractThe concentration of phosphorus‐containing metabolites was determined in extracts of multiple samples from six human breast tumours and in samples from normal and inflamed breast tissue. The degree of lymphoid infiltrate, necrotic fraction and tumour cell and normal tissue fraction were determined on sections taken from each of the tumour samples. In four of the tumours there was a very high degree of variation between samples in the absolute concentration of metabolites. Three of these tumours showed a high degree of intra‐tumour variation in the distribution of tumour cells and of normal tissue. The other two tumours were relatively homogeneous with respect to both tumour cellularity and the distribution of phosphorus‐containing metabolites. Samples from normal breast tissue was found to contain only low concentrations of phosphorus‐containing metabolites. However one of the inflamed samples, which consisted predominantly of macrophages, contained high levels of such compounds. The effect of time delay between resection and freezing on the levels of metabolites in human breast tumours was also examined.
31P NMR and enzymatic analysis of cytosolic phosphocreatine, ATP, Pi and intracellular pH in the isolated working perfused rat heart
Authors: Dobson Geoffrey P. , Veech Richard L. , Passonneau Janet V. , Kobayashi Kumpai , Inubushi Toshiro , Wehrli Susanna , Nioka Shoko , Chance Britton 
Published: March 2007

AbstractHearts from fed male Wistar rats (200–350 g) were perfused at low and high workloads with Pi‐free Krebs‐Henseleit medium containing either 10 mM glucose or 10 mM glucose plus 15mU/mL insulin. The intracellular pH by 31P NMR ranged between 6.99 and 7.02 and agreed to within 0.1 pH unit of estimates calculated using enzymatically determined total tissue HCO3−/CO2 contents. At high work, where the tissue contents of phosphocreatine (PCr) and ATP were determined on the same heart as NMR areas (n = 16), the proportionality factors, defined as the 31P NMR area units divided by the total enzymatically determined tissue content (area units/μmol/g dry wt), were 112±8 for PCr, 99±4 for γ‐ATP, 138±9 for α‐ATP and 100±4 for β‐ATP. These values were normalized by taking β‐ATP as 100 area units/μmol/g dry wt. Since the proportionality factor for PCr and γ‐ and β‐ATP were not statistically different (p < 0.05), it was concluded that each was equally visible by 31P NMR and that no significant breakdown of PCr occurred during freezing or tissue acid extraction procedures. The cytosolic Pi estimated from NMR in glucose plus insulin perfused hearts at low and high work was 4.92±0.67 and 6.33±0.42 μmol/g dry wt. Using the near‐equilibrium expression of KCK/KG+G and the metabolite levels in heart extracts, the calculated cytosolic Pi was 13.08±1.83 and 16.17±3.08 μmol/g dry wt, respectively. The cytosolic NMR Pi in the glucose hearts was 8.42±1.0 and 8.42±0.75 μmol/g dry wt at low and high work and 12.08±1.58 and 27.20±4.20±μmol/g dry wt from near‐equilibrium estimates. The total tissue Pi measured enzymatically on freeze‐clamped hearts ranged from 18.0 to 26.42 μmol/g dry wt. The validity of using both the 31P NMR and the near‐equilibrium method for estimating cytosolic Pi in the heart was discussed.
Evidence that mitochondrial phosphate is visible in 31P NMR spectra of isolated, perfused rat hearts
Authors: Garlick Pamela B. , Soboll Sibylle , Bullock Gillian R. 
Published: March 2007

AbstractWe had previously found (P. B. Garlick, T. R. Brown, R. H. Sullivan and K. Ugurbil, J. Mol. Cell Cardiol. 15, 855–858 (1983)) that two peaks could be observed in the phosphate region of NMR spectra of isolated, perfused rat hearts. Upon valinomycin treatment, an increase in the peak at 2.8 ppm in the phosphate region (phosphocreatine set at −2.52 ppm) had been observed. We have now confirmed our hypothesis that this peak originates from the mitochondrial phosphate by: (i) determination of myocardial mitochondrial phosphate contents using density gradient centrifugation in non‐aqueous solvents; and (ii) quantitative electron microscopy of the heart tissue. Thus, we conclude that mitochondrial and cytosolic phosphate can be distinguished from each other in 31P NMR spectra of isolated, perfused rat hearts.
Classification of tumour 1H NMR spectra by pattern recognition
Authors: Howells S. L. , Maxwell R. J. , Griffiths J. R. 
Published: March 2007

Abstract1H spectra of tumours or normal tissues, which include signals from all hydrogen‐containing metabolites, are too complex for the human eye to interpret. We have studied 58 1H spectra from perchloric acid extracts of three normal tissues (liver, kidney and spleen) and five rat tumours (GH3 pituitary, fibrosarcoma, Morris Hepatomas 7777 and 9618a and Walker carcinosarcoma). Instead of editing them or quantifying individual metabolites, we have used statistical pattern recognition techniques to classify them into groups. This automatic, objective method differentiated spectra from normal and malignant rat tissue biopsies, and from different types of cancer. It seems likely that this technique can be applied to human tissues and thus used for cancer diagnosis.
Identification of lactate, threonine and alanine in rat thymus and tumorigenic lymphoid cells using 1H 2‐D COSY NMR spectroscopy
Authors: Tang Hailun L. , Buist Richard J. , Rixon Raymond H. , Whitfield James F. , Smith Ian C. P. 
Published: March 2007

AbstractOne‐ and two‐dimensional 1H NMR spectra were obtained for normal murine thymus and malignant lymphoma tissue, as well as for the supernatant fractions from high speed centrifugal separations. Crosspeaks in the two‐dimensional spectra resembled those reported by others for adenocarcinoma and leukemic lymphoblast cells, assigned tentatively to the carbohydrate fucose. However, for the present systems, spectral analysis and the spectral response to addition of known compounds led to assignment of the crosspeaks as follows: 1.33–4.12 ppm, lactate anion; 1.33–4.26 ppm, threonine; 1.48–3.78 ppm, alanine. Differences between the NMR data for the normal and malignant specimens were only in the relative intensities of the peaks. No peaks characteristic of fucose were found in spectra of cytosol, tissue or membrane lipids. Thus, the NMR data for malignant lymphoma cells are significantly different from those for adenocarcinoma and leukemic lymphoblasts. The NMR characteristics of different types of cancer cell must be individually determined.
Quantitative magnetic resonance spectroscopy by optimized numerical curve fitting
Authors: Webb S. , Collins D. J. , Leach M. O. 
Published: March 2007

AbstractA technique is reported for generating the quantitative area under selected peaks within a 31P NMR spectrum. A numerical iterative method generates the fitted curve so as to minimize the RMS deviation between the fit and the experimental data. The curve is constructed from elemental grains of spectral density (“spexels”), each of which represents an elemental Lorentzian distribution, where the centre frequency and line width of the spexel may be varied within predetermined limits. This provides a fit that in principle is not restricted to a Lorentzian model. The method allows peak areas to be estimated, including the case of overlapping peaks. The method has been tested using simulated spectra containing six overlapping spectral lines each of known amplitude (ranging from 367 to 661 mV) and area; together with additional Gaussian noise with a standard deviation ranging from 30 to 646 mV. The results of fitting both unfiltered and filtered spectra were compared. The variation of quality of fit with spectral noise and filtering has been evaluated. In all cases, the method fitted the peak amplitudes to within 1% of the simulated value. The optimization processes provide an excellent non‐linear spectrum filtering algorithm. Provided the noise in the spectra did not exceed ca 400 mV, prefiltered data could be adequately fitted.
A two‐point volume localized T1 measurement sequence for in vivo spectroscopy using a surface coil
Authors: Yongbi N. M. , Leach M. O. , Payne G. S. , Collins D. J. 
Published: March 2007

AbstractA technique for obtaining T1 values from well localized regions using surface coils and with a clinically practicable measurement time is described. The method uses a two‐point Inversion‐Recovery/Saturation‐Recovery (IR/SR) sequence in conjunction with the image‐selected in vivo spectroscopy localization scheme. T1 values are obtained by comparing the ratio of peak areas with those in a pre‐computed look‐up table. The method was tested by measuring the T1s of six calibrated water phantoms doped with different concentrations of gadolinium. This indicated an accuracy of 3% for T1 values in the range 400‐1500 ms. 31P spectra and T1 values of Pi, phosphocreatine and α‐, β‐ and γ‐NTP metabolites from the calf muscle of healthy volunteers were obtained with the sequence employing Bi‐insensitive excitation pulses and a surface coil. The T1 values fall within the range of published values obtained by other techniques.
General features of systemic effects of murine leukemias on phosphate metabolism in liver studied by 31P NMR
Authors: Yushmanov Victor E. , Khristianovich Darya S. , Rozantseva Tatyana V. , Sibeldina Lili A. 
Published: March 2007

Abstract31P NMR was used to study the systemic effects of a tumor on a host organism by monitoring the phosphate metabolite content in freshly excised mouse liver at 0–4°C and in ethanolic liver extracts of animals suffering from La, L1210 and P388 leukemias and Ehrlich ascites tumor (EAT). The progression of murine leukemia is characterized by increases in the intensities of the resonances of Pi and phosphomonoesters (PME), in particular, phosphorylethanolamine, in liver; phosphodiester (PDE) signals increase two‐ to four‐fold during the period of rapid tumor growth and decline to undetectable levels in the terminal stage. There were no reliable alterations detected in the ATP content and intracellular pH throughout the course of the leukemia. The kinetics of intracellular phosphates are similar in various kinds of leukemia but quite different in EAT. The reduction of inoculum causes the appearance of maxima in the Pi and PME profiles in the latent period of La leukemia, but the profiles of liver PDE considered from the end of the latent period are independent of inoculum. Possible mechanisms for the changes in PDE concentrations and their biochemical role are discussed. NMR spectroscopy of liver may be used to indirectly monitor the progression of tumors unavailable for direct NMR assay.
31P NMR spectroscopy of a xenografted hypopharynx carcinoma: Effects of tumor growth and treatment with cisplatin on the tumor phosphorus metabolism, histology and cytokinetics
Authors: Tausch‐Treml Robert , Baumgart Frank , Ziessow Dieter , Köpf‐Maier Petra 
Published: March 2007

AbstractA xenografted hypopharynx carcinoma growing subcutaneously in nude mice was studied by in vivo 31P NMR spectroscopy during uninfluenced growth and following treatment with cisplatin (CDDP). Parallel to the NMR experiments, the cytokinetic and histological changes in the tumor were investigated. The most significant change in the growing tumor was a decline in the level of phosphocreatine (PCr), whereas the tumor pH did not change. Following treatment with CDDP (4, 8 and 12 mg/kg), a dose‐dependent decrease in the level of phosphomonoesters (PME) took place, whilst no dose dependence could be observed for the increase of PCr. the pH shifted to alkaline only after administration of the highest CDDP dose. Tumor cytokinetics revealed a cell arrest at the G1/S boundary 24 h after chemotherapy. At this time, the histological sections showed a dilatation of capillaries, whereas first necroses appeared on day 3. The proliferative activity of the tumor showed a sharp decline 24 h after CDDP application, followed by a revival of cell proliferation that was proportional to the dose applied between days 5 and 7. This increase in proliferative activity was paralleled by a marked increase in the PME/phosphodiesters ratio. Thus, in the tumor investigated the PME were the best indicators of tumor response to therapy. A precise correlation between the cytokinetic data and the re‐energization of the tumor was not possible because histological changes, which may contribute to improved tumor energy status took place at the same time.
Quantitation of metabolites in NMR spectra from isolated tissues, using 14N spectroscopy and nitrate to determine tissue volume
Authors: Wray S. , Wilkie D. R. 
Published: March 2007

AbstractQuantification of metabolites is a goal of many biomedical NMR studies. To obtain absolute measurements of metabolite concentrations is often both difficult and time‐consuming. In this paper a method for determining metabolite concentrations directly is described and validated. It is applicable to studies of amphibian muscles, and with suitable precautions, to other isolated organs and tissues. The method is based upon using 14N NMR and nitrate‐containing solutions to determine what fraction (F) of the sensitive volume of the RF coil is occupied by tissue. As the concentration of nitrate is known it can be used to calibrate other 14N metabolites in the tissue. Moreover, once F is determined, it can be used to calibrate metabolites in spectra from other nuclei e.g., 31P or 31C. All that is required is that a spectrum from a standard for that nucleus is obtained. Thus this method does not require any “internal” (intrinsic to the tissue) standard, and is extremely quick and simple to use.
31P NMR spectroscopy of perinatal hypoxic‐ischemic brain damage: A model to evaluate neuroprotective drugs in immature rats
Authors: William Gerald D. , Palmer Charles , Roberts Rebecca L. , Heitjan Daniel F. , Smith Michael B. 
Published: March 2007

AbstractCerebral energy metabolism can be measured non‐invasively in unanesthetized neonatal rats with 31P NMR spectroscopy. Using this technique, serial changes in high energy phosphates were determined from the right cerebral hemispheres of 7 day postnatal rat pups during a hypoxic‐ischemic insult known to produce focal brain injury. During 3 h of hypoxia‐ischemia the concentration of ATP dropped to 33±8% of prehypoxic (baseline) levels, phosphocreatine (PCr)/Pi decreased from 1.5±0.51 to 0.16±0.06, while pH decreased nominally by 0.2 units. After 2.5 h of recovery in air, ATP returned to 75±10% of baseline levels, PCr/Pi rose to 1.1±0.28, and pH returned to its normal value of 7.16±0.06. This model was used to test the efficacy of the adenosine deaminase inhibitor, 2‐deoxycoformycin (DCF) as a potential neuroprotective drug. The data for the drug‐ and saline‐treated populations were analyzed by integrating ATP and Pi/PCr levels over specific time intervals, expressing it relative to baseline levels, and modeling it with cubic splines. Pretreatment with 500 μg/kg DCF shows a small, but statistically significant, preservation of both ATP and phosphorylation potential during hypoxia and initial recovery. Brain water content (edema) at 42 h recovery was apparently associated with both mean ATP and mean Pi/PCr in the last 2 h of hypoxia‐ischemia. When ATP fell below 70% of baseline, brain edema was evident at 42 h of recovery. This methodology is suitable for extension to human infants.
Depth selective quantification of phosphorus metabolites in human calf muscle
Authors: Dunn J. F. , Kemp G. J. , Radda G. K. 
Published: March 2007

AbstractWe have used phase modulated rotating frame imaging, a depth selective NMR technique, in conjunction with two methods of calibration, in order to determine the feasibility of quantifying phosphorus compounds in selected regions of a biological sample. In one method, we related peak areas obtained from a sample to the peak area of an external reference located within the receiver coil, previously calibrated against a standard. In the second method we measured peak areas from a standard separately and related them directly to the area of the sample peak. We examined the calf muscles of male volunteers, positioning the coil to obtain signal mainly from the gastrocnemius in the shallow slices and soleus in the deep slices. The concentrations of Pi, phosphocreatine and ATP (in mmol/kg tissue) were 3.0±0.5, 18±2 and 4.8±0.2 at 2 cm depth (mean±SD; n = 5). These results are similar to published biopsy data. A comparison with published values obtained from other NMR quantification methods suggests that, while it is possible to obtain consistent results within one laboratory, it is not currently possible to obtain similar results between laboratories. This is evident from the fact that different laboratories report different phosphocreatine/ATP ratios, indicating that the techniques are limited by variations in the processes of data collection and peak area measurement.
Application of time‐domain fitting in the quantification of in vivo1H spectroscopic imaging data sets
Authors: de Beer R. , van den Boogaart A. , van Ormondt D. , Pijnappel W. W. F. , den Hollander J. A. , Marien A. J. H. , Luyten P. R. 
Published: March 2007

AbstractTime‐domain model function fitting techniques were applied to improve the reconstruction of metabolite maps from the data sets obtained from in vivo 1H spectroscopic imaging (SI) experiments. First, residual water‐related signals were removed from the SI data sets by using SVD‐based linear time‐domain fitting based upon the HSVD (State Space) approach. Second, peak integrals of the metabolites of interest were obtained by quantifying the proton spin‐echoes of the voxels by means of non‐linear time‐domain fitting based upon the maximum likelihood principle. Third, in order to save computational time, interpolation of the metabolite images (from size 32 × 32 to 128 × 128) was performed in the image‐domain by applying one‐dimensional cubic splines. It was found that the residual water signals can be almost completely removed from the SI data sets by applying the linear HSVD fitting method. Furthermore, it was found that voxel dependency of certain NMR parameters (e.g., variations of the spin‐echo offset frequencies and/or phase factors) can be accounted for automatically by applying the non‐linear time‐domain fitting technique. For that purpose it appeared to be essential to employ prior knowledge of the NMR spectral parameters.
Phosphorus metabolite characterization of human prostatic adenocarcinoma in a nude mouse model by 31P magnetic resonance spectroscopy and high pressure liquid chromatography
Authors: Kurhanewicz John , Dahiya Rajvir , Macdonald Jeffrey M. , Jajodia Prahalad , Chang Lee‐Hong , James Thomas L. , Narayan Perinchery 
Published: March 2007

AbstractA series of experiments were conducted to identify and quantify the phosphorus metabolites of DU 145 xenografts (a human prostatic adenocarcinoma cell line grown in nude mice) using 31P MRS and HPLC. The 31P spectral characteristics of DU 145 xenografts were compared to perfused DU 145 cells and to in situ human prostatic adenocarcinomas. These studies demonstrated that both DU 145 xenografts and perfused DU 145 cells exhibited reduced levels of phosphocreatine relative to spectra of in situ human prostatic adenocarcinomas. Elevated levels of phosphomonesters (PMEs) were observed in 31P spectra of both DU 145 xenografts and in situ human prostatic adenocarcinomas. The major components of the PME resonance of DU 145 xenografts were identified as phosphocholine and phosphoethanolamine. High levels of diphosphodiesters (DPDEs) were consistently observed for both DU 145 xenografts and perfused DU 145 cells, but were absent in 31P spectra of in situ primary human adenocarcinomas. In agreement with spectroscopic results, high pressure liquid chromatographic analyses of human tissue removed at surgery contained insignificant amounts of DPDEs while DU 145 xenografts had high levels of DPDEs consisting mainly of uridine‐5′‐diphospho‐N‐acetylgalactosamine (22.4 nmol/mg protein) and uridine‐5′‐diphospho‐N‐acetylglucosamine (7.4 nmol/mg protein).
An assessment of 31P MRS as a method of measuring pH in rat tumours
Authors: Stubbs M. , Bhujwalla Z. M. , Tozer G. M. , Rodrigues L. M. , Maxwell R. J. , Morgan R. , Howe F. A. , Griffiths J. R. 
Published: March 2007

AbstractThe contribution of extracellular components to the measurement of pHMRS of a variety of rat tumours (nitrosomethyl urea induced mammary tumours, GH3 prolactinomas, Hepatoma 9618a, UA hepatomas and Walker sarcomas) has been assessed. Acid extractable Pi was between 2.6 and 12.5 μmol/g wet wt depending on tumour type, and of this 53±4.8% (mean ± SEM) was MRS‐visible. The Pi content of tumour exudate was 2–3 mM, of interstitial fluid (sampled from a micropore chamber incorporated within a tumour) 1.7 mM, and of blood plasma 1.95 mM. The mean extracellular volumes of the tumours, measured by distribution of 3H2O and [14C]inulin, were 49‐55% depending on tumour type and were at least twice that found in normal liver. Calculations suggested that for most tumours with an extracellular volume not exceeding 55%, at least 65% of the Pi(MRS) signal was derived from intracellular Pi, and thus that pHMRS is a measure of pHi. For each tumour type, pHMRS was measured both in “pulse‐acquire” mode at 1.9T which may include signals from surrounding tissue, and in localized mode at 4.7 T where the signal came uniquely from tumour tissue. The steady state pHMRS was either neutral or on the alkaline side of neutrality (pH range 7.04–7.37). Raised lactate content and decreased buffering capacity (compared to normal tissues) accompanied these neutral to alkaline pH values. The extracellular pH of all the tumour types was found to be significantly lower than pHi when calculated from the distribution of lactate across the plasma membrane ([lactate−]out/[lactate−]in = [H+]in/[H+]out) by the method of Veech [Veech, R. L. NMR Biomed. 4, 53–58 (1991)] whereas in control tissue (liver) the extracellular pH was higher, as would be expected.