J M Pearce

University of Arkansas at Little Rock, Little Rock, Arkansas, United States

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Publications (13)56.39 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: It has been hypothesized that schizophrenia arises from cell membrane abnormalities due to changes in phospholipid (PL) composition and metabolism. We have used high resolution, in vitro 31P nuclear magnetic resonance (NMR) to characterize the PLs in left frontal cortex (gray matter) of postmortem brain from four schizophrenics and five controls. High resolution 31P NMR spectra were obtained in an organic-solvent system to resolve PL classes (headgroups) and in a sodium-cholate, aqueous dispersion system to resolve phosphatidylcholine (PC) molecular species. Multivariate analysis which included the major PC molecular species and phosphatidylinositol (PI) showed a significant difference between schizophrenics and controls. Analysis of specific interactions showed that the PI was significantly higher in the schizophrenic group than in the control group. There were no differences between the two groups for other individual PL classes, or for individual PL subclasses determined by the linkage type at the sn-1 position on glycerol. There was a trend for total PL content to be higher in schizophrenics than in controls. There was no evidence for elevated lysophosphatidylcholine or lysophosphatidylethanolamine in schizophrenia. The intensity of the PC peak representing molecular species with one saturated and one unsaturated (one or two double bonds) acyl chain was higher for the schizophrenic group than for the control group. Although these results are not in complete agreement with previous studies, they support the idea that PL abnormalities occur in the brain in schizophrenia and that fatty acid metabolism may be abnormal.
    Psychiatry Research 06/2001; 106(3):171-80. DOI:10.1016/S0925-4927(01)00081-6 · 2.68 Impact Factor
  • J M Pearce · R A Komoroski
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    ABSTRACT: Techniques are described for the (31)P NMR analysis of glycerophospholipid (PL) headgroup and molecular species in brain. The (31)P NMR spectrum of PLs from human temporal cortex, solubilized in aqueous Na cholate, typically showed 3 major resonances, assigned to phosphatidylcholine (PC) molecular species containing 0, 1, or 2 fully saturated acyl chains. Less species resolution was obtained for the other PL headgroups under these conditions. Alkylacyl- and alkenylacyl-PC were readily discerned using the CHCl(3)-CH(3)OH-H(2)O solvent method. The chain-length, temperature, and species dependences of the (31)P NMR chemical shifts were explored in model PLs. Assignments of signals from phosphatidylethanolamine (PE) subclasses were confirmed in the sodium-cholate system by lipase-mediated selective hydrolysis of bovine-brain PE. The utility of (31)P NMR to monitor enzymatic PL oxidation was further demonstrated. Possible changes in PL composition with postmortem interval (PMI) in rat brain were examined. No significant changes were seen in PL headgroup or PC species composition with PMI at up to 18 hours. Where comparable, the Na-cholate-solubilization and solvent methods gave similar quantitative results for headgroup analysis on the same samples. The present work demonstrates the feasibility and utility of the dual system for analysis of PLs in brain. Magn Reson Med 44:215-223, 2000.
    Magnetic Resonance in Medicine 09/2000; 44(2):215-23. DOI:10.1002/1522-2594(200008)44:2<215::AID-MRM8>3.0.CO;2-N · 3.40 Impact Factor
  • Biological Psychiatry 04/2000; 47(8). DOI:10.1016/S0006-3223(00)00327-9 · 10.25 Impact Factor
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    ABSTRACT: The use of nuclear magnetic resonance (NMR) spectroscopy as a method for drug analysis has the advantages of reduced pre-analytical preparation time and the potential to detect and quantitate drug conjugates and metabolites simultaneously. NMR was investigated as a method to screen for organic substances (and metabolites) in 25 patients who presented to the Emergency Department with clinical indications of a drug overdose. Urine specimens were examined by 1H NMR spectroscopy at 300 MHz and the results compared with gas chromatography-mass spectrometry (GC-MS) results. There was a 56% concordance (14 of 25 samples) between NMR and GC-MS. NMR identified acetaminophen, ibuprofen, aspirin, valproate, carbamazepine, and pseudoephedrine as parent compounds or metabolites. For a patient for whom GC-MS results were negative, NMR strongly suggested the presence of erythromycin. NMR was most successful in identifying analgesics and antiepileptic drugs (sensitivity 83-100%). In 10 patients, signals from 1,2-propanediol, a common vehicle for some pediatric medications, were observed by NMR spectroscopy. NMR had 0% sensitivity in identifying tricyclic antidepressants and antipsychotic drugs. In these samples, GC-MS detected a variety of compounds, including tricyclic antidepressants and their metabolites and chlorpromazine. In addition, other substances that had not been disclosed as having been ingested, such as caffeine, diphenhydramine, and nicotine, were detected by GC-MS. NMR spectroscopy represents an emerging supplementary analytical technique that is applicable to a wide range of possible intoxicants and to the evaluation of the intoxicated patient, particularly when larger amounts of the intoxicant (> 200 mg) are ingested.
    Journal of analytical toxicology 04/2000; 24(3):180-7. DOI:10.1093/jat/24.3.180 · 2.63 Impact Factor
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    ABSTRACT: Some evidence suggests that thalamic dysfunction could explain some of the signs and symptoms of schizophrenia. We measured the absolute concentrations of amino acid metabolites in thalamus, frontal pole, and cerebellar vermis in extracts of postmortem brains from 8 schizophrenics and 10 controls using high-resolution 1H-magnetic resonance spectroscopy. The concentrations of N-acetyl aspartate, glutamate, and valine tended to be reduced in the thalamus of the schizophrenic group. Although it is difficult to ascribe significance to the “tendencies,” these data may tend to support other data suggesting decreased thalamic volume or neuronal number in schizophrenia.
    Biological Psychiatry 10/1997; 42(5-42):359-366. DOI:10.1016/S0006-3223(96)00409-X · 10.25 Impact Factor
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    ABSTRACT: The regional distribution of lithium (Li) in vivo was determined on a relative basis in the brain and muscle of rats by 7Li NMR imaging. Both high resolution 7Li NMR spectroscopy and atomic absorption spectrophotometry were performed on extracts of brain and muscle tissue from the same rats. The average in vivo results were generally in good agreement with the corresponding average in vitro results, despite the relatively low signal-to-noise ratio of the in vivo images. There was good agreement between the two in vitro methods of analysis, both on average and for individual animals. Significant differences were found in vivo among Li concentration ratios for the various brain regions and muscle by 7Li imaging, as well as by the in vitro methods.
    Magnetic Resonance in Medicine 08/1997; 38(2):275-8. DOI:10.1002/mrm.1910380217 · 3.40 Impact Factor
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    ABSTRACT: Fluorine-19 NMR spectroscopy was used to monitor the anti-depressant drug fluoxetine (and its metabolite norfluoxetine) in vivo in human brain. A quadrature birdcage head coil, developed for operation at 60.1 MHz, yielded a signal from the head 2 to 4 times stronger than for surface coils. It was used to measure the in vivo 19F spin-lattice relaxation time (T1) of fluoxetine for five patients by the inversion-recovery technique. The individual T1s varied from 149 to 386 ms, which was attributed in part to interindividual differences based on the reproducibility of a phantom T1. The individual T1 correlated weakly with approximate brain concentration. A lower limit of 3 to 4 ms was found for the spin-spin relaxation time from line width measurements. Low resolution 4-dimensional spectroscopic imaging confirmed that the single in vivo 19F resonance for fluoxetine arose primarily from brain. The spectrum of a cerebral hemisphere (in formalin) obtained at autopsy from a patient on 40 mg/day of fluoxetine for 19 weeks was comparable with that seen for patients in vivo. The in vivo signal arose about equally from fluoxetine and the active metabolite norfluoxetine, as demonstrated by the in vitro 19F NMR spectrum of the lipophilic extract of a small section of brain. In vitro quantitation of frozen samples from three brain regions yielded combined fluoxetine/norfluoxetine concentrations of 12.3 to 18.6 micrograms/ml, which is higher than typically determined in vivo, and suggests that the fluorinated drugs may not be 100% visible in vivo.
    Magnetic Resonance in Medicine 03/1994; 31(2):204-11. · 3.40 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Fluorine-19 NMR spectroscopy was used to monitor the anti-depressant drug fluoxetine (and its metabolite norfluoxetine) in vivo in human brain. A quadrature birdcage head coil, developed for operation at 60.1 MHz, yielded a signal from the head 2 to 4 times stronger than for surface coils. It was used to measure the in vivo19F spin-lattice relaxation time (T1) of fluoxetine for five patients by the inversion-recovery technique. The individual T1s varied from 149 to 386 ms, which was attributed in part to interindividual differences based on the reproducibility of a phantom T1. The individual T1 correlated weakly with approximate brain concentration. A lower limit of 3 to 4 ms was found for the spin-spin relaxation time from line width measurements. Low resolution 4-dimensional spectroscopic imaging confirmed that the single in vivo19F resonance for fluoxetine arose primarily from brain. The spectrum of a cerebral hemisphere (in formalin) obtained at autopsy from a patient on 40 mg/day of fluoxetine for 19 weeks was comparable with that seen for patients in vivo. The in vivo signal arose about equally from fluoxetine and the active me tabolite norfluoxetine, as demonstrated by the in vitro19F NMR spectrum of the lipophilic extract of a small section of brain. In virto quantitation of frozen samples from three brain regions yielded combined fluoxetine/norfluoxetine concentrations of 12.3 to 18.6 μ/ml, which is higher than typically determined in vivo, and suggests that the fluorinated drugs may not be 100% visible in vivo.
    Magnetic Resonance in Medicine 02/1994; 31(2):204 - 211. DOI:10.1002/mrm.1910310214 · 3.40 Impact Factor
  • J M Pearce · J T Krone · A A Pappas · R A Komoroski
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    ABSTRACT: A technique using solubilization with sodium cholate to resolve 31P NMR resonances of phospholipid molecular species was applied to amniotic fluid samples from 16 subjects. Gestational ages from 25 to 40 weeks were represented, and two subjects were sampled sequentially. Fitting of the partially resolved 31P NMR signal of phosphatidylcholine (PC) generated an estimate of percent disaturated acyl PC (%dsPC) which correlated more highly with gestational age than did several other potential indices of fetal lung maturation, such as the ratio of PC to inorganic phosphate from the solubilized spectra, or PC to sphingomyelin from extract spectra. In a few cases, enzyme-catalyzed PC hydrolysis limited the precision, but did not appear to affect the accuracy, of the %dsPC estimates. Resolution of palmitoyl and oleoyl lyso-PC species was observed for both the 1- and 2-acyl isomers. Upfield shifts due to the presence of cis double bonds in the lone acyl chain of the lyso-PCs were analogous to those observed for the diacyl PCs.
    Magnetic Resonance in Medicine 10/1993; 30(4):476-84. DOI:10.1002/mrm.1910300410 · 3.40 Impact Factor
  • J M Pearce · R A Komoroski
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    ABSTRACT: Phosphorus-31 NMR chemical shifts of phospholipids (PLs) solubilized in bile salts were studied with respect to variations in the structure of the acyl substituents. The presence of double bonds in the acyl chains of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and phosphatidic acid (PA) induced small but consistent upfield shifts relative to the corresponding disaturated acyl PL signals. The magnitudes of the unsaturation-related upfield shifts were approximately twice as large in sodium cholate as in sodium deoxycholate. Chemical shift separations of PC, PE, and PG dipalmitoyl-dioleoyl species pairs increased slightly at lower temperatures. Resolution of the PC species pair was maximized and nearly independent of cholate-to-PL ratio at values greater than about 100 in 2% cholate. Only the PA species resolution varied significantly over the pH range 6.5 to 9.5, in the vicinity of its pK2. Shift differences for a homologous series of disaturated acyl PCs showed a logarithmic dependence on chain length. Spectra for a variety of PC standards were used to interpret the composite PC signals from egg yolk extract, soybean extract and whole human amniotic fluid. The 31P NMR analyses were consistent with published chromatographic studies. Interpretation of composite PL signals in the cholate system is simplified for mixtures having restricted acyl chain length and degree of unsaturation.
    Magnetic Resonance in Medicine 07/1993; 29(6):724-31. · 3.40 Impact Factor
  • J. M. Pearce · R. A. Komoroski
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    ABSTRACT: Phosphorus-31 NMR chemical shifts of phospholipids (PLs) solubilized in bile salts were studied with respect to variations in the structure of the acyl substituents. The presence of double bonds in the acyl chains of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and phosphatidic acid (PA) induced small but consistent upfield shifts relative to the corresponding disaturated acyl PL signals. The magnitudes of the unsaturation-related upfield shifts were approximately twice as large in sodium cholate as in sodium deoxycholate. Chemical shift separations of PC, PE, and PG dipalmitoyl-dioleoyl species pairs increased slightly at lower temperatures. Resolution of the PC species pair was maximized and nearly independent of cholate-to-PL ratio at values greater than about 100 in 2% cholate. Only the PA species resolution varied significantly over the pH range 6.5 to 9.5, in the vicinity of its pK2. Shift differences for a homologous series of disaturated acyl PCs showed a logarithmic dependence on chain length. Spectra for a variety of PC standards were used to interpret the composite PC signals from egg yolk extract, soybean extract and whole human amniotic fluid. The 31P NMR analyses were consistent with published chromatographic studies. Interpretation of composite PL signals in the cholate system is simplified for mixtures having restricted acyl chain length and degree of unsaturation.
    Magnetic Resonance in Medicine 06/1993; 29(6):724-731. DOI:10.1002/mrm.1910290603 · 3.40 Impact Factor
  • J M Pearce · M A Shifman · A A Pappas · R A Komoroski
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    ABSTRACT: A recently described solvent-reagent system for obtaining narrow linewidths in 31P NMR spectra of phospholipid extracts was applied to human amniotic fluid. Resolution of the major components was achieved by manipulating the solvent composition, and assignments were made by spiking samples with standard compounds. Spin-lattice relaxation times were determined and used to optimize data acquisition. NMR estimates of the phosphatidylcholine to sphingomyelin ratio for 33 patients were compared to those obtained by TLC densitometry, a common clinical assay for fetal pulmonary maturity. Estimates of the levels of phosphatidylglycerol and phosphatidylinositol could also be obtained from 31P NMR. High-resolution 31P NMR in this solvent-reagent system provides a relatively straightforward and reliable alternative method for assessing fetal pulmonary status by phospholipid quantitation in human amniotic fluid. The 31P NMR method has the advantage that it is sensitive to total, and not just unsaturated, phosphatidylcholine.
    Magnetic Resonance in Medicine 10/1991; 21(1):107-16. · 3.40 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A recently described solvent-reagent system for obtaining narrow linewidths in 31P NMR spectra of phospholipid extracts was applied to human amniotic fluid. Resolution of the major components was achieved by manipulating the solvent composition, and assignments were made by spiking samples with standard compounds. Spin-lattice relaxation times were determined and used to optimize data acquisition. NMR estimates of the phosphatidylcholine to sphingomyelin ratio for 33 patients were compared to those obtained by TLC densitometry, a common clinical assay for fetal pulmonary maturity. Estimates of the levels of phosphatidylglycerol and phosphatidylinositol could also be obtained from 31P NMR. High-resolution 31P NMR in this solvent-reagent system provides a relatively straightforward and reliable alternative method for assessing fetal pulmonary status by phospholipid quantitation in human amniotic fluid. The 31P NMR method has the advantage that it is sensitive to total, and not just unsaturated, phosphatidylcholine. © 1991 Academic Press, Inc.
    Magnetic Resonance in Medicine 09/1991; 21(1):107-116. DOI:10.1002/mrm.1910210113 · 3.40 Impact Factor