phosphorus-radioisotopes and phosphorylethanolamine

Magnetic resonance spectroscopy (MRS) remains the technique of choice for observing tumour metabolism non-invasively. Although initially 31P MR spectroscopy showed much promise as a non-invasive diagnostic tool, studies of a wide range of hepatic tumours have conclusively shown that this technique cannot be utilized to distinguish between different tumour types. This lack of specificity and sensitivity appears to be a consequence of the fact that hepatic tumours develop with a range of modalities and not as a single abnormal disease process, and also because of the limited availability of MR detectable metabolic markers. This has led, in recent years, to a re-evaluation of the role of 31P MR spectroscopy, re-emerging as a non-invasive tool to follow the efficacy of the treatment regime. Furthermore, since the principal changes observed in tumours by 31P MRS appear to be an elevation in the concentration of phosphorylcholine (PCho) and phosphoethanolamine (PEth), new research using a combination of MRS and tissue culture of cell lines which carry a combination of known inducible oncogenes, are helping to elucidate some of the metabolic pathways that give rise to these metabolic alterations.

Topics: Ethanolamines; Humans; Liver Neoplasms; Magnetic Resonance Spectroscopy; Phospholipids; Phosphorus Radioisotopes; Phosphorylcholine

Phosphorus-31 (31P) NMR is proving to be a powerful analytical method for investigating molecular/metabolic issues in neural tissues. Recent studies have demonstrated high levels of phosphomonoesters and phosphodiesters in mammalian brain, and revealed the influence of brain maturation, development, and aging on these levels. Preliminary studies in Alzheimer's disease have demonstrated elevated levels of phosphomonoesters and phosphodiesters in the areas of Alzheimer's brain which exhibit neuropathological changes. Moreover, phosphomonoester levels were also elevated in areas of Alzheimer's brain that were devoid of neuropathological changes. These findings suggest that the phosphomonoester elevations in Alzheimer's brain antedate changes in cellular morphology and structure. Abnormalities in protein kinase function could potentially explain these findings, as well as the reported hyperphosphorylation of tau protein in Alzheimer's brain. Recent studies from this laboratory suggest that aluminum could also be involved in the changes in phosphomonoesters and phosphodiesters.

Topics: Aging; Alzheimer Disease; Animals; Brain; Ethanolamines; Humans; Magnetic Resonance Spectroscopy; Organophosphates; Organophosphorus Compounds; Phosphorus Radioisotopes; Phosphorylcholine; Rats; Rats, Inbred F344

To determine what biochemical changes may occur in the brain in Williams syndrome (WS) and whether these changes may be related to the cognitive deficits.. WS is a rare, congenital disorder with a characteristic physical, linguistic, and behavioral phenotype with known cognitive deficits.. We obtained 31P magnetic resonance spectra (MRS) from a region consisting of mostly frontal and parietal lobe of 14 patients with WS (age, 8 to 37 years) and 48 similarly-aged controls. 1H MRS (27 cm3) localized to the left cerebellum obtained from the WS cohort were compared with those from 16 chronological age- and sex-matched normal controls. A battery of cognitive tests were administered to all subjects undergoing 1H MRS.. WS brains exhibited significant biochemical abnormalities. All 31P MRS ratios containing the phosphomonoester (PME) peak were significantly altered in WS, suggesting that PME is significantly decreased. Ratios of choline-containing compounds and creatine-containing compounds to N-acetylaspartate (Cho/NA and Cre/NA) were significantly elevated in the cerebellum in WS cf. controls, whereas the ratio of Cho/Cre was not altered. This suggests a decrease in the neuronal marker N-acetylaspartate in the cerebellum. Significant correlations were found between the cerebellar ratios Cho/NA and Cre/NA and the ability of all subjects at various neuropsychological tests, including Verbal and Performance IQ, British Picture Vocabulary Scale, Ravens Progressive Matrices, and Inspection Time.. The correlations can be interpreted in two ways: 1) Our sampling of cerebellar biochemistry reflects a measure of "global" cerebral biochemistry and is unrelated to cerebellar function, or 2) The relations indicate that cerebellar neuronal integrity is a requirement (on a developmental time scale or in real-time) for ability on a variety of cognitive tests.

Topics: Adenosine Triphosphate; Adolescent; Adult; Brain Chemistry; Cerebellum; Child; Cognition; Ethanolamines; Female; Frontal Lobe; Glycerophosphates; Hexosephosphates; Humans; Inositol Phosphates; Magnetic Resonance Spectroscopy; Male; Neuropsychological Tests; Parietal Lobe; Phosphocreatine; Phosphorus Radioisotopes; Phosphorylcholine; Phosphoserine; Protons; Radionuclide Imaging; Williams Syndrome

31P NMR brain spectra were obtained from piglets over a range of mild hypocarbia to severe hypercarbia (PaCO225 to 198 mm Hg). The chemical shifts of the phosphoethanolamine and inorganic phosphate were used to calculate intracellular brain pH (pHet and pHpi, respectively). Both pHpi and pHet underwent parallel significant decreases during hypercarbia, corresponding to 51 and 53% pHregulation, respectively. We conclude that the chemical shift of the phosphomonoester peak in vivo can be used to measure decreases in intracellular pH in neonatal brain.

Topics: Acidosis; Animals; Animals, Newborn; Brain; Carbon Dioxide; Ethanolamines; Magnetic Resonance Spectroscopy; Partial Pressure; Phosphorus Radioisotopes; Swine

Topics: Adrenal Gland Neoplasms; Biopsy; Ethanolamines; Female; Humans; Infant, Newborn; Liver; Liver Neoplasms; Magnetic Resonance Spectroscopy; Neuroblastoma; Phosphocreatine; Phosphorus Radioisotopes

Krebs II ascite cells suspended in Eagle medium were incubated at 37 C for up to 6 hr in the presence of [3H] glycerol or [32P] orthophosphate. After extraction, their lipids were treated with guinea pig phospholipase A1 under conditions where all diacyl-phospholipids (diacyl-PL) became hydrolyzed with 55% recovery of lyso-PL. Using a bidimensional thin layer chromatography (TLC) involving exposure to HCl fumes between the two runs, it then became possible to determine at once the specific radioactivity of the three subclasses (diacyl-, alkylacyl- and alkenylacyl-) present in choline glycerophospholipids (CGP) and ethanolamineglycerophospholipids (EGP). Compared to diacyl-PL, a lower de novo synthesis of ether subclasses was evidenced in both CGP and EGP by [3H] glycerol incorporation. Although the same profile was obtained for CGP with [32P] orthophosphate, the three EGP subclasses displayed in this case the same specific radioactivity. These data indicate a higher turnover rate of the polar head group of ether-EGP compared to either-CGP. The simple methodology used in the present study might thus prove helpful in developing enzymatic studies dealing with the mechanism of this accelerated renewal.

Topics: Animals; Carcinoma, Krebs 2; Choline; Deoxycholic Acid; Ethanolamines; Glycerol; Kinetics; Mice; Phosphates; Phospholipids; Phosphorus Radioisotopes; Phosphorylcholine; Tritium