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Biomedical subjects

J A Stanley

Publications and source records attributed to J A Stanley.

At least 19 recordsLinked to original sources
PubMed2003

Prefrontal membrane phospholipid metabolism of child and adolescent offspring at risk for schizophrenia or schizoaffective disorder: an in vivo 31P MRS study.

In vivo (31)P magnetic resonance spectroscopy ((31)P MRS) studies have shown abnormal membrane phospholipid metabolism in the prefrontal cortex (PF) in the early course of schizophrenia. It is unclear, however, whether these alterations also represent premorbid risk indicators in schizophrenia. In this paper, we report in vivo (31)P MRS data on children and adolescents at high risk (HR) for schizophrenia. In vivo (31)P MRS studies of the PF were conducted on 16 nonpsychotic HR offspring of parents with schizophrenia or schizoaffective disorder, and 37 age-matched healthy comparison (HC) subjects. While 11 of the HR subjects had evidence of Axis I psychopathology (HR-P), five HR subjects had none (HR-NP). We quantified the freely mobile phosphomonoester (PME) and phosphodiester (PDE) levels reflecting membrane phospholipid precursors and breakdown products, respectively, and the relatively broad signal underlying PDE and PME peaks, comprised of less mobile molecules with PDE and PME moieties (eg, synaptic vesicles and phosphorylated proteins). Compared to HC subjects, HR subjects had reductions in freely mobile PME; the differences were accounted for mainly by the HR-P subjects. Additionally, HR-P subjects showed increases in the broad signal underlying the PME and PDE peaks in the PF. To conclude, these data demonstrate new evidence for decreased synthesis of membrane phospholipids and possibly altered content or the molecular environment of synaptic vesicles and/or phosphoproteins in the PF of young offspring at risk for schizophrenia. Follow-up studies are needed to examine the predictive value of these measures for future emergence of schizophrenia in at-risk individuals.

Adolescent↗
PubMed2001

Postprocessing method to segregate and quantify the broad components underlying the phosphodiester spectral region of in vivo (31)P brain spectra.

In a typical, in vivo (31)P brain spectrum, the phosphomonoester (PME) and phosphodiester (PDE) spectral region not only contains signals from freely mobile PMEs and PDEs (which are anabolic and catabolic products of membrane phospholipids) but also signals of broader underlying lineshapes from less-mobile molecules. In general, either the PME and PDE resonances are quantified as a combined value of freely mobile metabolites plus less-mobile molecules or the broader underlying signal is reduced/eliminated prior to or post data collection. In this study, a postprocessing method that segregates and quantifies the individual contributions of the freely mobile metabolites and the less-mobile molecules is introduced. To demonstrate the precision and accuracy of the method, simulated data and in vivo (31)P brain spectroscopy data of healthy individuals were quantified. The ability to segregate and quantify these various PME and PDE contributions provides additional spectral information and improves the accuracy of the interpretation of (31)P spectroscopy results. Magn Reson Med 45:390-396, 2001.

Adult↗
PubMed2000

Molecular insights into neurodevelopmental and neurodegenerative diseases.

Magnetic resonance spectroscopy (MRS) is a non-invasive physical technique that is routinely used to determine the quantity and structure of organic molecules in solution. Technical advances that have expanded the usefulness of this technique include: (1) high resolution MRS to identify and quantify individual molecules present in complex mixtures of tissue extracts; (2) in vivo MRS techniques to non-invasively monitor metabolites in humans; (3) structure determination of proteins of moderate size; and (4) improved structure characterization of solids and liquid crystals, such as the detection of phase changes in membranes. The focus of this review is on the first two technical advances mentioned above. The strengths of MRS as a research tool to investigate molecular alterations in disease states include ease of sample preparation, minimum sample manipulation, avoidance of the preparation of derivatives, and the ability to analyze an unfractionated sample. The strengths of MRS in the clinic are its ability to measure neuronal metabolite levels non-invasively in humans and its potential for disease diagnosis, monitoring disease progression, and assessing the efficacy of experimental therapies.

Aging↗
PubMed2000

Magnetic resonance spectroscopy in schizophrenia: methodological issues and findings--part II.

Magnetic resonance spectroscopy allows investigation of in vivo neurochemical pathology of schizophrenia. "First generation" studies, focusing on phosphorus and proton magnetic resonance spectroscopy, have suggested alterations in membrane phospholipid metabolism and reductions in N-acetyl aspartate in the frontal and temporal lobes. Some discrepancies remain in the literature, perhaps related to the variations in medication status and phase of illness in the patients examined, as well as in magnetic resonance spectroscopy methodology; the pathophysiologic significance of the findings also remains unclear. Technologic advances in magnetic resonance spectroscopy in recent years have expanded the potential to measure several other metabolites of interest such as the neurotransmitters glutamate and gamma-aminobutyric acid and macromolecules such as membrane phospholipids and synaptic proteins. Issues of sensitivity, specificity, measurement reliability, and functional significance of the magnetic resonance spectroscopy findings need to be further clarified. The noninvasive nature of magnetic resonance spectroscopy allows longitudinal studies of schizophrenia both in its different phases and among individuals at genetic risk for this illness. Future studies also need to address confounds of prior treatment and illness chronicity, take advantage of current pathophysiologic models of schizophrenia, and be hypothesis driven.

Animals↗
PubMed2000

Magnetic resonance spectroscopy in schizophrenia: methodological issues and findings--part I.

Our knowledge of the biological basis of schizophrenia has significantly increased with the contribution of in vivo proton and phosphorus magnetic resonance spectroscopy (MRS), a noninvasive tool that can assess the biochemistry from a localized region in the human body. Studies thus far suggest altered membrane phospholipid metabolism at the early stage of illness and reduced N-acetylaspartate, a measure of neuronal volume/viability in chronic schizophrenia. Inconsistencies remain in the literature, in part due to the complexities in the MRS methodology. These complexities of in vivo spectroscopy make it important to understand the issues surrounding the design of spectroscopy protocols to best address hypotheses of interest. This review addresses these issues, including 1) understanding biochemistry and the physiologic significance of metabolites; 2) the influence of acquisition parameters combined with spin-spin and spin-lattice relaxation effects on the MRS signal; 3) the composition of spectral peaks and the degree of overlapping peaks, including the broader underlying peaks; 4) factors affecting the signal-to-noise ratio; 5) the various types of localization schemes; and 6) the objectives to produce accurate and reproducible quantification results. The ability to fully exploit the potentials of in vivo spectroscopy should lead to a protocol best optimized to address the hypotheses of interest.

Animals↗
PubMed1998

Proton magnetic resonance spectroscopic imaging in patients with extratemporal epilepsy.

PURPOSE: Reduced levels of N-acetylaspartate (NAA) in temporal lobes responsible for temporal lobe epilepsy have been observed consistently in proton magnetic resonance spectroscopy (MRS) studies. METHODS: We investigated the potential of proton MRS to detect low NAA outside of the temporal lobes in patients with non-lesional partial extratemporal epilepsy. Proton MR spectroscopic imaging (MRSI) data of both frontal lobes and central/postcentral regions were obtained in 20 such patients and 16 normal control subjects. The epileptogenic region was determined by an extensive clinical-EEG investigation, including the recording of habitual seizures in each patient, and intracranial EEG recordings in 10 patients. RESULTS: The relative NAA resonance intensities (i.e., NAA/phosphocreatine plus creatine (CR(t)), NAA/choline-containing metabolites (Cho(t)) and NAA/Cr(t) + Cho(t)), were all significantly reduced throughout the spectroscopic image as compared with that of the controls. Furthermore, reduction of the NAA ratios was greater in the epileptogenic region as compared with the nonepileptogenic regions, on EEG investigation. CONCLUSIONS: In vivo proton MRSI of patients with nonlesional partial extratemporal epilepsy detected evidence of widespread neuronal damage or dysfunction that was greatest in the region of seizure focus.

Adult↗
PubMed1997

Magnetic resonance spectroscopic changes in Alzheimer's disease.

In vitro and in vivo 31P magnetic resonance (MR) spectroscopy studies of Alzheimer's disease (AD) brain have revealed alterations in membrane phospholipid metabolism and high-energy phosphate metabolism. Mildly demented AD patients compared with control subjects have increased levels of phosphomonoesters, decreased levels of phosphocreatine and probably adenosine diphosphate and an increased oxidative metabolic rate. As the dementia worsens, levels of phosphomonoesters decrease and levels of phosphocreatine and adenosine di-phosphate increase. The changes in oxidative metabolic rate suggest that the AD brain is under energetic stress. The phosphomonoester findings support our in vitro findings and implicate basic defects in membrane metabolism in AD brain. MR spectroscopy provides new diagnostic insights and a noninvasive method to follow the progression of the disease and the metabolic response to therapeutic interventions.

Alzheimer Disease↗
PubMed1997

Proton magnetic resonance spectroscopic imaging for discrimination of absence and complex partial seizures.

We performed proton magnetic resonance spectroscopic imaging of the temporal lobes between, during, and soon after nonconvulsive seizures in 20 patients with documented temporal lobe epilepsy, 5 patients with primary generalized epilepsy, and 2 patients with secondary generalized epilepsy. Our objective was to determine whether there were metabolic changes observable by magnetic resonance spectroscopic imaging during seizures and whether these changes were specific for focal or generalized nonconvulsive seizures. We found a significant increase in lactate to creatine plus phosphocreatine (lactate/creatine) values, reflecting an imbalance in energy supply and demand or an adaptation in response to ictal neuronal discharges, during and soon after complex partial seizures, but not during or soon after absence seizures associated with generalized epilepsy. In patients with temporal lobe epilepsy, the N-acetylaspartate resonance relative to creatine plus phosphocreatine was low in one or both temporal lobes, indicating neuronal loss or damage. This was not observed in patients with primary generalized epilepsy. The regions with abnormal lactate/creatine and N-acetylaspartate/creatine values corresponded to the epileptogenic focus as defined by clinical-electroencephalographic investigation. There was no change in the N-acetylaspartate/creatine values in the temporal lobes between the interictal, ictal, or postictal states. We conclude that (1) partial seizures are associated with abnormally high lactate levels, but absence seizures are not, and (2) no short-term changes of N-acetylaspartate occur during or soon after complex partial seizures or absence seizures. These findings may be related to the lack of postictal confusion in patients with absence seizures, as well as with the more benign course of primary generalized epilepsy with nonconvulsive attacks.

Adolescent↗
PubMed1997

Aggregation of beta-amyloid peptide is promoted by membrane phospholipid metabolites elevated in Alzheimer's disease brain.

Increased amounts of beta-amyloid (A beta) peptide deposits are found in Alzheimer's disease brain. These amyloid deposits have been implicated in the pathophysiology of this common dementing illness. A beta peptides have been shown to be toxic to neurons in cell culture, and this toxicity is critically dependent on the aggregation of the peptide into cross-beta-pleated sheet fibrils. Also, in vivo and postmortem NMR studies have shown changes in certain brain membrane phospholipid metabolites in normal aging and more extensive alterations in patients with Alzheimer's disease. The finding that membrane phospholipids affect the aggregation of A beta suggests that the abnormalities in membrane metabolism found in Alzheimer's disease could affect the deposition of A beta in vivo. Therefore, we examined the effect of membrane phospholipid metabolites that are altered in Alzheimer's disease brain on the aggregation of A beta(1-40) using a light scattering method. Certain metabolites (glycerophosphocholine, glycerophosphoethanolamine, and alpha-glycerophosphate) augment the aggregation of A beta. Other membrane phospholipid metabolites (phosphocholine, phosphoethanolamine, and inositol-1-phosphate) have no effect. We conclude that increased membrane phospholipid metabolite concentrations may play a role in the deposition of A beta seen in normal aging and the even greater deposition of A beta observed in Alzheimer's disease.

Alzheimer Disease↗
PubMed1997

Magnetic resonance imaging volumetric and phosphorus 31 magnetic resonance spectroscopy measurements in schizophrenia.

The purpose of this study was to examine the relationship between phosphorus magnetic resonance spectroscopy (31P MRS) parameters and left prefrontal volumes in both patients with schizophrenia and healthy subjects. 31P MRS parameters and magnetic resonance imaging (MRI) volumetric data were collected in the left prefrontal region in 10 patients with schizophrenia and 10 healthy subjects of comparable age, handedness, sex, educational level, and parental educational level. No correlations were found between any MRS parameter and grey matter volumes in the combined subjects. Phosphomonoester (PME) and grey matter volumes, however, were both correlated negatively with age. PMEs were found to be decreased, and calculated intracellular magnesium ([Mg2+]intra) was found to be increased in the patients with schizophrenia compared with healthy subjects after adjusting for left prefrontal grey and white matter, total brain volume, and age. These findings suggest that cortical grey and white manner volumes are not directly related to PME and [Mg2+]intra abnormalities in schizophrenia patients.

Adult↗
PubMed1996

An in vivo proton magnetic resonance spectroscopy study of schizophrenia patients.

The level of the 1H metabolites in the left dorsolateral prefrontal region of schizophrenia patients at different stages of illness were measured in vivo using a short echo time spectroscopy technique. During both the early onset and chronic stages, normal N-acetylaspartate levels were observed, which suggests that these patients had no significant neuronal cell damage and/or loss. The in vivo measurements of glutamate in the first-episode, drugnaive patients failed to provide convincing evidence for the involvement of the glutamatergic system in the dorsolateral prefrontal region. Significant differences in the glutamine levels were observed in the acutely medicated and chronic patients; however, the interpretation of these differences requires further study.

Adolescent↗
PubMed1995

An in vivo study of the prefrontal cortex of schizophrenic patients at different stages of illness via phosphorus magnetic resonance spectroscopy.

BACKGROUND: In this study, phospholipid metabolism of cell membranes, high-energy phosphate metabolism, and intracellular free magnesium concentration in the prefrontal cortex of first-episode drug-naive schizophrenic patients and medicated schizophrenic patients at different stages of illness were compared with those of controls. METHODS: Localized in vivo phosphorus 31 magnetic resonance spectra of the left dorsolateral prefrontal cortex of 11 drug-native, eight newly diagnosed medicated, and 10 chronic medicated patients with schizophrenia were compared with controls of similar gender, education, parental education, and handedness. RESULTS: Significantly decreased levels of phosphomonoesters in drug-native, newly diagnosed medicated, and chronic medicated patients and significantly increased levels of phosphodiesters in drug-native patients were observed when compared with controls. There were no significant differences in the levels of high-energy phosphate metabolites between the groups except for a significant decrease in the inorganic orthophosphate levels of newly diagnosed medicated patients. A significant increase in the intracellular free magnesium concentration was observed in drug-naive, newly diagnosed medicated, and chronic medicated patients compared with controls. There were no correlations between the patients' negative and positive symptoms and the observed phosphorus-containing metabolites. CONCLUSIONS: A reduction in precursors of membrane phospholipid are observed during the early and chronic stages of the schizophrenia illness, and breakdown products of membrane phospholipids are increased at the early stage of illness before medication treatment.

Adolescent↗
PubMed1995

The use of a priori knowledge to quantify short echo in vivo 1H MR spectra.

In vivo 1H MR spectra of the prefrontal cortex acquired with the stimulated echo acquisition mode (STEAM) TE = 20 ms sequence were quantified to determine relative levels of cerebral metabolites. A priori knowledge of spectra from individual metabolites in aqueous solution was incorporated into a frequency domain quantification technique. The accuracy and precision of modeling these metabolites were investigated with simulated spectra of varying signal-to-noise ratios (SNRs) and relative metabolite levels. The efficacy of modeling in vivo data was tested by quantifying 10 repeated measures of two consecutively acquired in vivo spectra (an 8-cm3 volume of interest (VOI) and a 4-cm3 VOI positioned within the 8-cm3 VOI) on the same normal subject. The differences in levels of glutamate (Glu), phosphocreatine plus creatine (PCr+Cr) and choline-containing compounds (Cho(t)) between spectra from the 8- and 4-cm3 VOIs corresponded with the expected differences observed in the proportions of gray matter within the VOIs (estimated from 1H images). Correcting for the T1 and T2 relaxation, the estimated concentrations of N-acetylaspartate, PCr+Cr, Cho(t), Glu, and glutamine were consistent with previous in vivo and in vitro reports.

Adult↗
PubMed1994

Membrane phospholipid metabolism and schizophrenia: an in vivo 31P-MR spectroscopy study.

Membrane phospholipid metabolism was studied with 31P magnetic resonance spectroscopy in the left dorsal prefrontal cortex of 19 male, medicated, schizophrenic patients and compared to 18 normal male controls matched in age, education and parental education level. The schizophrenic patients had significantly decreased phosphomonoester levels (PMEs, metabolites predominantly involved in the synthesis of membrane phospholipids). Phosphodiester levels (PDEs, breakdown products of membrane phospholipids) were not statistically different in schizophrenic patients compared to controls. However, a significant increase in the PDE levels was observed in the newly diagnosed patient subgroup. This observed pattern of the PMEs and PDEs would be consistent with the presence of an abnormal neurodevelopment early in the illness of schizophrenia.

Adolescent↗
PubMed1988

Protection from radiation-induced damage to spermatogenesis in the androgen pretreated rat.

Protection of spermatogenesis from radiation-induced damage has been investigated in the adult Wistar rat. Silastic tubing containing either cholesterol or testosterone was implanted subcutaneously 7 weeks before 4 equal daily fractions of either 1, 1.5, 2, and 2.5 Gy of 230 kVp X-rays locally to the testes. Implants were removed on the day following the last fraction and 8 weeks after irradiation 88.6%, 83.8%, 63.6% and 28.9% tubule cross-sections respectively were found regenerating in rats pretreated with testosterone. In contrast, 68.45%, 58.6%, 38.2% and 17.3% tubule cross-sections regenerating were obtained in rats pretreated with cholesterol. Changes in testis weight however were found to show the reverse trend (i.e. a greater weight loss was observed following androgen pretreatment). These results show that protection of spermatogenesis from fractionated irradiation may be achieved in rat testis by androgen pretreatment.

Animals↗
PubMed1987

Time dependence for the protective effect of androgen from procarbazine-induced damage to rat spermatogenesis.

The protective effects of androgen pretreatment on the procarbazine-induced killing of spermatogonial stem cells in Wistar rats have been investigated. Using testosterone-filled Silastic implants (200 mm2) the degree of protection from four weekly doses of procarbazine (100 mg/kg) was found to be dependent upon the androgen pretreatment time interval as assessed by quantitative histology. No protective effect was seen until rats had received 4 wk of pretreatment with androgen, whereafter protection increased to a maximum (about 20 to 30% of tubule cross-sections exhibiting recovery) after 8 to 12 wk of pretreatment. In contrast, the same level of maximal protection could be obtained by 6 wk of pretreatment using testosterone enanthate, suggesting that differences in protection may be achieved using different modes of androgen administration.

Androgens↗