Biomedical subjects

I L Kwee

Publications and source records attributed to I L Kwee.

At least 37 records · Page 2Linked to original sources

PubMed1992

In vivo 1H and 31P NMR spectroscopy of the developing rat brain.

The biochemical changes associated with brain maturation during the first 28 days postnatal were investigated utilizing proton and phosphorus-31 nuclear magnetic resonance spectroscopy in rat pups in vivo. Phosphocreatine was found to increase linearly during this period of development. Phosphomonoester was high at birth, peaked around the 10th day postnatal, and declined thereafter. N-Acetyl-aspartate was low at birth, increased in an approximately linear fashion, and reached adult levels by about Day 28 postnatal. Choline was high at birth and declined thereafter. Taurine, a sulfur amino acid abundant in fetal brain, was also present in high levels on the first day postnatal.

Adenosine Triphosphate↗

PubMed1992

Brain maturation and response to anoxia: 31P NMR spectroscopic studies in rat pups.

The differential effects of systemic anoxia on the immature rat brain in two postnatal developmental age groups, group I (1-2 days postnatal) and group II (9-10 days postnatal), were studied utilizing phosphorus-31 nuclear magnetic resonance spectroscopy. While all pups in group I survived the 15-min anoxic period, only half of the pups in group II survived. Brain adenosine triphosphate and intracellular pH of pups in group I remained essentially unchanged throughout the anoxic period, while phosphocreatine and inorganic phosphate were sensitive indicators of anoxia. These parameters were all more drastically affected in group II pups than in group I pups. Group II pups also exhibited a significant increase in phosphomonoester, indicating developmental differences in phospholipid metabolism.

Adenosine Triphosphate↗

PubMed1992

T1 values of phosphomonoester and phosphocreatine of brain show no significant change during development.

Changes in apparent 31P spin-lattice relaxation times (T1) associated with brain development were investigated in rat pups. While analysis of variance showed strong age dependency in [PME]/[ATP] and [PCr]/[ATP], the T1 values of PME, PCr, and ATP did not show any age dependency. The studies indicate that in contrast to the data which indicated aging-related changes in the T1 values of PME, the observed changes in PME during neonatal development are likely to be quantitative in nature.

Adenosine Triphosphate↗

PubMed1992

Brain pH and lactic acidosis: quantitative analysis of taurine effect.

A quantitative analysis of taurine effect (facilitation of acid handling capacity of brain in response to anoxia/hypoxia by high levels of cytosolic taurine) was performed utilizing multinuclear (1H, 31P) in vivo nuclear magnetic resonance (NMR) spectroscopy and in vitro titration analysis. Taurine effects observed in vivo showed excellent quantitative agreement with the predicted values estimated based on brain taurine levels. The study confirmed that high levels of cytosolic taurine indeed facilitate acid buffering capacity of brain and this taurine effect can be readily explained by the physical, and need not involve metabolic, properties of taurine. Taurine appears to be a key component of the brain cytosol system in the fetus.

Acidosis, Lactic↗

PubMed1992

Role of visuo-vestibular interaction in pathological ocular oscillation: new model and control system analysis.

Control system engineering is a relatively newer field of engineering which is directly applicable to performance analysis of neuronal networks. Visuo-vestibular interaction (VVI) represents a neuronal control system which has most benefited from such analysis. In this paper, we present a new model of VVI derived from our previously reported model by adding cortical pursuit feedback. Mathematical analysis of abnormal eye oscillations and stability analysis of the VVI system provided us with a plausible hypothesis that the pathological ocular oscillations seen in oculopalatal myoclonus and see-saw nystagmus are indeed due to an unstable VVI control system. The former is due to degeneration of the inferior olivary nucleus resulting in loss of cerebellar learning effects, while the latter is due to disruption of the pathway conveying retinal error signals.

Animals↗

PubMed1991

Rebound alkalosis and persistent lactate: multinuclear (1H, 13C, 31P) NMR spectroscopic studies in rats.

Intracellular pH levels of infarcted brain determined by phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy disclosed a notable phenomenon. The acidotic brain pH seen in the acute stage of infarction was observed to rebound into the alkalotic range in the subacute phase before returning to the normal range in the chronic phase. This "rebound alkalosis" which was usually observed between the 24th and the 48th hour after experimental induction of infarction in rats was accompanied by significant lactate levels as detected by proton NMR spectroscopy. Analysis of the satellite methyl resonance of 13C-lactate using high-resolution proton NMR spectroscopy after 13C-glucose infusion indicated that no lactate was produced in the subacute phase of infarction and that the lactate detected during this phase must have been generated prior to this phase of infarction.

Alkalosis↗

PubMed1991

31P NMR spectroscopy of 9L cell line in culture: differential effects of high temperature on anchored cells and spheroids.

The differential effects of high temperature on 9L rat gliosarcoma cells cultured in two distinctive forms, namely, anchored monolayer cells and multicellular spheroids, were investigated using 31P nuclear magnetic resonance spectroscopy. The critical temperatures resulting in irreversible changes in cellular energetics were found to be significantly different: 45 degrees C for anchored cells and 43 degrees C for multicellular spheroids, respectively. Phosphomonoester levels in multicellular spheroids were found to be consistently higher than those in anchored monolayer cells regardless of the temperature to which they were exposed. The study demonstrates that tissue derived from a single cell line may exhibit different metabolic properties depending on its growth pattern.

Animals↗

PubMed1991

Elevation in relative levels of brain membrane unsaturated fatty acids in Alzheimer's disease: high resolution proton spectroscopic studies of membrane lipid extracts.

Unsaturation indices of cerebral cortex membrane phospholipids in Alzheimer's disease were determined utilizing high resolution proton nuclear magnetic resonance (NMR) spectroscopy of lipid extracts. The unsaturation index of Alzheimer's brain was found to be significantly higher (P less than 0.01) than that of age-matched controls. The study provides further support for the hypothesis that alteration in phospholipid metabolism, especially an elevation in unsaturated fatty acids, may play a role in the pathogenesis of Alzheimer's disease.

Aged↗

PubMed1991

pH-lactate dissociation in neonatal anoxia: proton and 31P NMR spectroscopic studies in rat pups.

The pH controlling capability of brain of 1-day-old rat pups was investigated using proton (1H) and phosphorus-31 (31P) nuclear magnetic resonance (NMR) in vivo spectroscopy. Despite significantly high levels of lactate accumulation, brain of 1-day-old pups showed remarkable capability of maintaining brain pH virtually unchanged throughout 22 min of anoxia. The study supports the concepts that lactic acidosis is one of the important factors determining the outcome of cerebral anoxia and that the significantly higher pH controlling capability of immature brain plays a key role in the higher resistance toward anoxia.

Animals↗

PubMed1991

31P and 3-fluoro-3-deoxy-D-glucose 19F in vivo NMR spectroscopy of aged rat brain.

31P and 3-fluoro-3-deoxy-D-glucose (3-FDG) 19F nuclear magnetic resonance (NMR) spectroscopic investigations were performed on aged rat brain in vivo. Phosphodiester (PDE) was found to be significantly higher (p less than 0.05) in aged brain (18 months, n = 10) than adult controls (6 months, n = 10) suggesting accelerated phospholipid catabolism in aged brain. Inorganic phosphate (Pi) levels were significantly lower (p less than 0.05) in aged brain (n = 5) than in normal adult controls (n = 5). The sorbitol index, a measure of aldose reductase activities in vivo, determined by the 3-FDG 19F NMR method, revealed that aldose reductase activities were significantly higher (p less than 0.05) in aged brain.

Aging↗

PubMed1991

pH-lactate dissociation during anoxic insult: taurine effect.

Taurine, a sulfur amino acid abundant in brain of the fetus and early day neonate, has been postulated to play a major role in mediating the immature brain's unusually high buffering ability for lactic acidosis reported previously. In this study, we directly investigated this 'taurine effect' using a 10-day-old rat pup model and multinuclear (31P and 1H) nuclear magnetic resonance (NMR) in-vivo spectroscopy. Brain of taurine-supplemented pups exhibited significantly higher acid buffering ability against lactic acidosis than age-matched control pups. The study supports the hypothesis that high levels of free cytosolic taurine increase the brain's ability to buffer against lactic acidosis.

Adenosine Triphosphate↗

PubMed1991

Maturational changes in intracellular high energy phosphate transport in rat brain.

Maturational changes in intracellular high energy phosphate (HEP) transport in brain were investigated in rats in vivo using 31P nuclear magnetic resonance (NMR) diffusion spectroscopy and saturation transfer experiments. The diffusivities of phosphocreatine (PCr) and adenosine triphosphate (ATP) in adult brain were significantly higher than in newborn pup brain. The estimated diffusion lengths of PCr and ATP were similar in adult and newborn pup brain. The findings indicate firstly that the faster diffusivities of HEP effectively compensates for the higher energy demands in adult brain and secondly that ATP diffusion appears sufficient for brain HEP transport without need for a PCr shuttle mechanism.

Aging↗

PubMed1990

Membrane fatty acid composition shows delta-6-desaturase abnormalities in Alzheimer's disease.

Brain membrane phospholipid fatty acid composition is investigated in Alzheimer's disease using fresh pathologically proven autopsy material. The most striking abnormalities in Alzheimer brains compared to age-matched controls are found in the n - 6 line of polyunsaturated fatty acids (PUFA) showing an elevation of 18:2 (n - 6) associated with a reduction of 20:4 (n - 6) and 22:4 (n - 6). The findings strongly indicate abnormalities in delta 6-desaturation. The decrease in 22:6 (n - 3) also supports delta 6-desaturase abnormalities. Alteration in PUFA desaturation/elongation processes and resultant membrane abnormalities may play a key role in the pathogenesis of Alzheimer's disease.

Aged↗

PubMed1990

Persistent high lactate level as a sensitive MR spectroscopy indicator of completed infarction.

Serial proton (1H) and phosphorus-31 (31P) magnetic resonance (MR) spectroscopy of cerebral infarction was performed in rats to assess the sensitivity of these techniques for use in clinical cerebral infarction. In this experimental chronic infarction model, 31P spectroscopy tended to return to a "normal" pattern within 24 hours after induction of infarction in spite of pathologically proven completed infarction and, therefore, appeared not to be sensitive enough for clinical application. On the other hand, proton spectroscopy invariably showed persistent high lactate levels and was capable of distinguishing completed infarction from reperfused recovered brain. Persistent high lactate levels appear to be a good MR spectroscopic indicator of completed infarction.

Animals↗

PubMed1989

Intrauterine fetal brain NMR spectroscopy: 1H and 31P studies in rats.

Fetal brain metabolism was investigated in utero noninvasively using multinuclear nuclear magnetic resonance spectroscopy in rats at two representative prenatal stages: early (17-18 days) and late (20-21 days) stages. Phosphorus-31 (31P) spectroscopy revealed that phosphocreatine is significantly lower in the early stage and increases to the level of early neonates by the late prenatal stage. Intracellular pH at the early stage was found to be strikingly high (7.52 +/- 0.21) and decreased to a level similar to that of neonates by the late stage (7.29 +/- 0.07). Phosphomonoester levels at both stages were similar to the values reported for early neonates. Water-suppressed proton (1H) spectroscopy demonstrated a distinctive in vivo fetal brain spectral pattern characterized by low levels of N-acetyl aspartate and high levels of taurine. High-resolution proton spectroscopy and homonuclear chemical-shift correlate spectroscopy of brain perchloric acid extracts confirmed these in vivo findings. In vitro 31P spectroscopy of acidified chloroform methanol extracts showed the characteristic membrane phospholipid profiles of fetal brain. The phosphatidylethanolamine (PE)-to-phosphatidylcholine (PC) ratio (PE/PC) did not show significant changes between the two stages at 0.40 +/- 0.11, a value similar to that of early neonates.

Animals↗

PubMed1989

Cortical spectroscopy: localized spectroscopy of the cerebral cortex in rats.

A method for obtaining nuclear magnetic resonance (NMR) spectroscopic signals confined to the cerebral cortex in rat using a cortical coil constructed based on the principles of the zig-zag coil is described. We obtained 31P NMR spectra of normal cerebral cortex and cold-induced injured cortex using this cortical coil. The cortical coil clearly demonstrated an increase in inorganic phosphate (Pi) confirmed to cerebral cortex which, by contrast, the conventional planar surface coil failed to detect. There are significant metabolic differences between cortex and subcortical tissues. The technique described here, capable of assessing cortical metabolism in vivo without contamination by the underlying tissue, has substantial application to studies of cerebral metabolism.

Animals↗

PubMed1989

In vivo pharmacokinetics of aldose reductase inhibitors: 3-fluoro-3-deoxy-D-glucose NMR studies in rat brains.

Direct quantification of the inhibitory effects of orally administered drugs (sorbinil, cyclandelate and sulindac) on aldose reductase activities in rat brains was performed non-invasively using the 3-fluoro-3-deoxy-D-glucose (3-FDG) 19F NMR spectroscopic technique. Quantitative data obtained directly from the target organ (brain) allowed for unprecedentedly accurate analysis of drug effects in the brain in vivo. Sorbinil, a potent aldose reductase inhibitor, exhibited a classic monophasic organ response, whereas cyclandelate and sulindac showed biphasic suppression patterns. The latter indicate that there are metabolites of these drugs which possess aldose reductase inhibitory activities. The estimated potency of aldose reductase inhibition for each of the three drugs in this study was significantly discrepant from the in vitro studies indicating the complicated nature of the bioavailability of a pharmaceutical agent in vivo, especially where pharmacologically active metabolites of a given drug are involved. Our method allows for a direct quantitative assay and hence the most reliable technique for evaluating aldose reductase inhibitory activities in the target organ.

Aldehyde Reductase↗

PubMed1989

31P magnetic resonance spectroscopy of chronic cerebral infarction in rats.

The chronological changes in the pattern of 31P magnetic resonance spectroscopy (MRS) associated with cerebral infarction were studied in rats. 31P MRS of chronic infarction (1 month after induction of infarction) clearly showed a pattern distinct from that of normal brain. In chronic infarction, the relative phosphomonoester (PME) level was found to be significantly higher and relative phosphocreatine (PCr) level significantly lower compared to normal brain. The intracellular pH and the relative inorganic phosphate (Pi) level did not show any significant differences. Histological examination indicated that the 31P MRS pattern of chronic infarction reflects gliosis.

Animals↗