Responsible aquaculture can aid food problems.
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Animals↗
Biomedical subjects
J D Bell
Publications and source records attributed to J D Bell.
Investigation of human low-density lipoprotein by (1)H nuclear magnetic resonance spectroscopy: mobility of phosphatidylcholine and sphingomyelin headgroups characterizes the surface layer.
The resolution of the trimethyl headgroup resonance of phosphatidylcholine (PC) and sphingomyelin (SM) in the intact human low-density lipoprotein (LDL) (1)H NMR spectrum at 600 MHz enabled the investigation of LDL surface structure and phospholipid-apoB interactions. We have previously shown that a higher proportion of PC headgroups (25-35% of total PC in LDL) compared to SM were tightly bound to apoB and therefore NMR-invisible [Murphy, H. C., et al. (1997) Biochem. Biophys. Res. Commun. 234 (3), 733-737]. In the present study, we have investigated the mobility of phospholipid (PL) headgroups, using (1)H NMR spin-spin (T(2)) relaxation measurements, in LDL isolated from nine volunteers. We show that both PC and SM exist in two additional and distinct environments indicated by the biexponential behavior of the relaxation decays in each case. The data showed that 36% of PC headgroups had a short T(2) component, mean T(2) of 31 ms, and 64% had a longer T(2) component of 54 ms. Approximately 15% of SM headgroups had a short T(2) component (mean T(2) of 27 ms) and 85% had a longer T(2) component of 78 ms. Therefore the majority of SM headgroups (85%) were more mobile than PC (P < 0.001) and since PC headgroups in organic media were more mobile than SM, we conclude that the characteristic high mobility of LDL SM is not an intrinsic property but arises from a high degree of order in molecular packing of the surface PL of human LDL. We suggest that because PC and SM interact differentially with cholesterol and possibly with neighboring phospholipids, this results in the formation of relatively long-lived microdomains of PL in vivo.
Humans↗
Susceptibility of S49 lymphoma cell membranes to hydrolysis by secretory phospholipase A(2) during early phase of apoptosis.
During cell death, plasma membranes of cells become vulnerable to attack by extracellular secretory phospholipase A(2). The purpose of this study was to identify the timing of this phenomenon relative to other events that occur during the process of cell death. Death was induced in S49 murine lymphoma cells by treatment with dexamethasone, dibutyryl cAMP, ionomycin, thapsigargin, or heat shock (1 h at 43 degrees C). The appearance of membrane susceptibility to secretory phospholipase A(2) was compared to the following apoptotic events: loss of mitochondrial membrane potential, phosphatidylserine exposure in the outer leaflet of the cell membrane, early DNA damage assessed by the comet assay, and changes in cell size and internal complexity assessed by flow cytometry. Each inducer of death was distinct in the time course of events produced. Although dead cells were susceptible to the action of phospholipase A(2), live cells (impermeable to propidium iodide) also became vulnerable to the enzyme during characteristic time courses after exposure to each inducer. In fact, susceptibility to sPLA(2) was observed in each case prior to or concurrent with the earliest of the markers of apoptosis. These results demonstrate that the onset of susceptibility to sPLA(2) is an early event in apoptosis suggesting that changes in membrane structure may be relevant to initial aspects of the apoptotic process.
Animals↗
Bioenergetic targeting during organ preservation: (31)P magnetic resonance spectroscopy investigations into the use of fructose to sustain hepatic ATP turnover during cold hypoxia in porcine livers.
During liver preservation, ATP supplies become depleted, leading to loss of cellular homeostatic controls and a cascade of ensuing harmful changes. Anaerobic glycolysis is unable to prolong ATP production for a significant period because of metabolic blockade. Our aim was to promote glycolysis during liver cold hypoxia by supplying fructose as an additional substrate, compared to supplementation with an equivalent concentration of glucose. Porcine livers (two groups; n = 5 in each) were retrieved by clinical harvesting techniques and subjected to two cycles of cold hypoxia and oxygenated hypothermic reperfusion. In the second cycle of reperfusion, the perfusate was supplemented with either 10 mmol/L glucose (Group 1) or 10 mmol/L fructose (Group 2). During reperfusion in both groups, similar levels of ATP were detected by phosphorus magnetic resonance spectroscopy ((31)P MRS). However, during subsequent hypoxia, ATP was detected for much longer periods in the fructose-perfused group. The rate of ATP loss was sevenfold slower during hypoxia in the presence of fructose than in the presence of glucose (ATP consumption of -7.2 x 10(-3)% total (31)P for Group 1 versus -1.0 x 10(-3)% total (31)P for Group 2; P < 0. 001). The changes in ATP were mirrored by differences in other MRS-detectable intermediates; e.g., inorganic phosphate was significantly higher during subsequent hypoxia in Group 1 (45.7 +/- 2.7% total (31)P) than in Group 2 (33.7 +/- 1.1% total (31)P; P < 0. 01). High-resolution MRS of liver tissue extracts demonstrated that fructose was metabolized mainly via fructose 1-phosphate. We conclude that fructose supplied by brief hypothermic perfusion may improve the bioenergetic status of cold hypoxic livers by sustaining anaerobic glycolysis via a point of entry into the pathway that is different from that for glucose.
Adenosine Triphosphate↗
Preferential loss of visceral fat following aerobic exercise, measured by magnetic resonance imaging.
The aim of this study was to use whole-body magnetic resonance imaging (MRI) together with biochemical and anthropometric measurements to study the influence of regular moderate exercise with no dietary intervention on adipose tissue distribution in nonobese healthy women. We found significant decreases in both total (28.86+/-2.24 vs. 27.00+/-2.27 liters, P < 0.05) and regional fat depots (visceral fat: 1.68+/-0.21 vs. 1.26+/-0.18 liters, P < 0.01) using whole-body MRI despite no significant change in body weight, body mass index, or the waist-to-hip ratio. Interestingly, no changes in body fat content were found using anthropometry or impedance. There was a significant increase in high density lipoprotein cholesterol (1.58+/-0.06 vs. 1.66+/-0.08 mmol/L P < 0.02) following exercise although there were no changes in other blood lipids such as triglycerides. In summary, moderate aerobic exercise over a period of 6 mon resulted in a preferential loss in visceral fat in nonobese healthy women, and this may help to explain some of the health benefits associated with regular and moderate physical activity.
Adipose Tissue↗
In vivo evaluation of the effects of continuous exercise on skeletal muscle triglycerides in trained humans.
Magnetic resonance spectroscopy (1H MRS) and imaging (MRI) were used to investigate the effects of a bout of moderate prolonged exercise on intra (IMCL)- and extramyocellular lipid (EMCL) utilization in the soleus, tibialis anterior, and gastrocnemius muscles of five trained human subjects. MRI and 1H MRS measurements were obtained before and after a 90 min run on a calibrated treadmill at a velocity corresponding to 64 +/- 1.5% of each subjects' maximal rate of oxygen consumption. There were significant decreases in IMCL following exercise in the tibialis (pre: 22.37 +/- 4.33 vs. post: 15.16 +/- 3.25 mmol/kg dry wt; P < 0.01) and soleus (pre: 36.93 +/- 1.45 vs. post: 29.85 +/- 2.44 mmol/kg dry wt; P < 0.01) muscles. There was also a decrease in the gastrocnemius muscle, although this did not reach the level of significance (pre: 33.78 +/- 5.35 vs. post: 28.48 +/- 5.44 mmol/kg dry weight; P < 0.10). No significant changes were observed in EMCL or subcutaneous fat. In conclusion, this study showed that IMCL were significantly utilized in the tibialis and soleus muscles of aerobically endurance-trained humans. The absence of significant utilization of IMCL in the gastrocnemius may reflect differences in fiber type and/or intensity of contraction for each muscle group.
Adult↗
Activities and interactions among phospholipases A2 during thapsigargin-induced S49 cell death.
The purpose of this study was to determine the roles of calcium-dependent phospholipase A2 (cPLA2) and calcium-independent phospholipase A2 (iPLA2) in thapsigargin-induced membrane susceptibility to secretory phospholipase A2 (sPLA2) and programmed cell death. 3H-arachidonic acid release was observed in the presence of thapsigargin. This release was inhibited partially by an inhibitor of iPLA2 (BEL) and completely by an inhibitor of both cPLA2 and iPLA2 (MAFP) suggesting that these enzymes were active during apoptosis. The process of cell death did not require the activity of either enzyme since neither inhibitor impeded the progression of apoptosis. However, both inhibitors increased the susceptibility of the membrane to sPLA2 in the presence of thapsigargin. In the case of BEL, this effect appeared to involve direct induction of apoptosis in a sub-population of the cells independent of the action of iPLA2. In conclusion, the results suggested that cPLA2 and iPLA2 are active during thapsigargin-induced apoptosis in S49 cells and that cPLA2 tempers the tendency of the cells to become susceptible to sPLA2 during apoptosis.
Animals↗
Assessing gene expression in vivo: magnetic resonance imaging and spectroscopy.
Recent developments in magnetic resonance imaging and spectroscopy afford the possibility of detecting and assessing transfer, expression and subsequent therapeutic changes of effector or marker transgenes noninvasively. In the field of MR imaging, 'smart' MR contrast agents are being developed, so called because they change their conformational structure and in so doing induce MR detectable changes in a given tissue. These agents become 'switched on' in response to physiological changes brought about by the enzymatic action of a given gene product (enzymes), and are being developed for use in intact cells, isolated organs and animal models. Ultimately, these agents hold the promise of bridging the gap between the laboratory and the patient with noninvasive detection of transgene expression in vivo in man. Similarly, magnetic resonance spectroscopy is being developed as a noninvasive method to assess transgene expression indirectly by means of MR visible intracellular markers. These markers take the form of intracellular endo/exogenous metabolites associated with exogenous enzyme expression and function. Again, this technique will be applicable to a variety of different situations, from cell suspensions through to clinical imaging of the whole body. In this article the unique opportunities for laboratory-based and clinical studies afforded by MR techniques are discussed.
Animals↗
Cortical dysfunction in non-demented Parkinson's disease patients: a combined (31)P-MRS and (18)FDG-PET study.
Regional cerebral phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) was performed in 10 non- demented Parkinson's disease patients and nine age-matched control subjects. Five of the patients undergoing (31)P-MRS and four additional Parkinson's disease patients had cerebral 2-[(18)F]fluoro-2-deoxy-D-glucose PET ((18)FDG-PET), the results of which were compared with those of eight age-matched control subjects. All Parkinson's disease patients underwent neuropsychological testing including performance and verbal subtests of the Wechsler Adult Intelligence Scale-Revised, Boston Naming Test, Controlled Oral Word Association test (FAS Test) and California Learning Test to exclude clinical dementia. (31)P MR spectra from right and left temporo-parietal cortex, occipital cortex and a central voxel incorporating basal ganglia and brainstem were obtained. (31)P MR peak area ratios of signals from phosphomonoesters (PMEs), inorganic phosphate (P(i)), phosphodiesters (PDEs), alpha-ATP, gamma-ATP and phosphocreatine (PCr) relative to beta-ATP were measured. Relative percentage peak areas of PMEs, P(i), PDEs, PCr, and alpha-, beta- and gamma-ATP signals were also measured with respect to the total (31)P-MRS signal. Significant bilateral increases in the P(i)/beta-ATP ratio were found in temporoparietal cortex (P = 0.002 right and P = 0.014 left cortex) for the non-demented Parkinson's disease patients compared with controls. In the right temporoparietal cortex, there was also a significant increase in the mean relative percentage P(i) (P = 0.001). (18)FDG-PET revealed absolute bilateral reductions in glucose metabolism after partial volume effect correction in posterior parietal and temporal cortical grey matter (P < 0.01 and P < 0.05, respectively) for the Parkinson's disease group, using both volume of interest analysis and statistical parametric mapping. There were significant correlations between right temporoparietal P(i)/beta-ATP ratios and estimated reductions in performance IQ (r = 0.96, P < 0.001). Left temporoparietal P(i)/beta-ATP ratios correlated with full scale IQ and verbal IQ (r = -0.82, P = 0.006, r = -0.86, P = 0.003, respectively). In summary, temporoparietal cortical hypometabolism was seen in non-demented Parkinson's disease patients with both (31)P-MRS and (18)FDG-PET, suggesting that both glycolytic and oxidative pathways are impaired. This dysfunction may reflect either the presence of primary cortical pathology or deafferentation of striato-cortical projections. (31)P-MRS and (18)FDG-PET may both provide useful predictors of future cognitive impairment in a subset of Parkinson's disease patients who go on to develop dementia.
Aged↗
Increased availability of central benzodiazepine receptors in patients with chronic hepatic encephalopathy and alcohol related cirrhosis.
BACKGROUND/AIMS: To measure cerebral benzodiazepine receptor binding using (11)C-flumazenil positron emission tomography in patients with stable chronic hepatic encephalopathy, who were also characterised by proton magnetic resonance spectroscopy. METHODS: Six abstinent patients of mean age 61 years with alcohol related cirrhosis and grade I-II hepatic encephalopathy and 11 matched healthy volunteers were studied. Each patient's encephalopathy was defined according to clinical, psychometric, electroencephalographic, and magnetic resonance spectroscopy criteria. Using positron emission tomography, the brain volume of distribution of (11)C-flumazenil was obtained; this reflects benzodiazepine receptor availability. Proton magnetic resonance spectra were acquired at 1.5 T using a multivoxel technique; peak area ratios were calculated for choline, glutamine/glutamate, N-acetylaspartate, and creatine resonances. RESULTS: The mean volume of distribution of (11)C-flumazenil was significantly higher in the cortex, cerebellum, and the basal ganglia in the patients compared with controls (p<0.001). In the patient group, the mean glutamine/glutamate to creatine ratio was significantly increased and the mean choline to creatine ratio was significantly decreased in all brain areas, compared with healthy volunteers. However, the N-acetylaspartate to creatine ratio was unchanged compared with controls. CONCLUSIONS: The spectroscopy results reflect the cerebral metabolic derangement associated with hepatic encephalopathy. Stable grade I-II chronic hepatic encephalopathy in alcohol related cirrhosis may be associated with increased cerebral benzodiazepine receptor availability. However, a direct effect of previous chronic exposure to alcohol cannot be excluded.
Adult↗
Stimulation by interleukin-6 and inhibition by tumor necrosis factor of cortisol release from bovine adrenal zona fasciculata cells through their receptors.
Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) are synthesized and released from adrenal cells. Therefore, the effects of TNF-alpha and IL-6 on cortisol release from bovine zona fasciculata (ZF) cells were investigated. IL-6 (10-1000 pg/mL) significantly increased basal and adrenocorticotropic hormone (ACTH)-stimulated cortisol release in a concentration-dependent manner. This stimulatory effect of IL-6 became apparent at intervals as short as 4 h and continued through 24 h. IL-6 also potentiated the cortisol release stimulated by the adenylyl cyclase activator forskolin. By contrast, TNF-alpha (0.1-10 ng) inhibited basal and ACTH-stimulated cortisol release in a concentration-dependent manner. The inhibitory effects of TNF-alpha on cortisol release were significant at time intervals as short as 4 h and continued through 24 h. TNF-alpha inhibited forskolin-stimulated cortisol release. Binding studies demonstrated that ZF cells have IL-6 receptors (100 receptors/cell, Kd of 7.5 x 10(-11)) and TNF receptors (200 receptors/cell, Kd of 2.4 x 10(-9) M). Immunohistochemical analysis provided evidence that the majority of ZF cells have IL-6 receptors, TNF type 1 receptors, and TNF type 2 receptors. Because IL-6 and TNF-alpha are released from the adrenal cortex and these cytokines modify the release of cortisol from the ZF, IL-6 and TNF-alpha may play a paracrine or autocrine role in the regulation of adrenal function.
Adenylyl Cyclases↗
Conflicting MRI signals from gliosis and neuronal vacuolation in prion diseases.
Magnetic resonance imaging (MRI) has given inconsistent results when used as a non-invasive diagnostic tool for Creutzfeldt-Jakob disease (CJD). In order to understand this finding, we studied a hamster model of scrapie by in vivo MRI and histopathology. Vacuolation of neurones/neuropil and gliosis were found to correlate with hypo-intense and hyper-intense changes in the conventional T2-weighted MR images, respectively. These opposing effects were shown to give rise to normal images of a scrapie-affected brain undergoing severe neurodegeneration, and may underlie the variability of previous CJD MRI data.
Animals↗
Improved preservation solutions for organ storage: a dynamic study of hepatic metabolism.
BACKGROUND: Organ cold storage times may be extended by modifications to organ preservation solutions. METHODS: Three preservation solutions were investigated for their ability to maintain viable hepatic bioenergetics in stored pig livers: modified University of Wisconsin (mUW); mUW+adenosine (1.34 g/L), and mUW+ iloprost (10(-8)mol/L), a prostacyclin analogue. Using human liver retrieval and storage techniques, pig livers were stored on ice for either 2 or 16 hr, after which phosphorus-31 spectra were collected every 2 min during the period of cold ischemia and hypothermic reperfusion (HtR). During HtR, metabolite concentration changes associated with phosphomonoesters, inorganic phosphate, gamma-nucleotide triphosphate (NTP), and beta-NTP were measured for all solutions. RESULTS: After a 2-hr storage, beta-NTP regeneration in mUW+iloprost produced +57.7% (P<0.01) more beta-NTP, at a faster initial rate of +66.3% (P<0.001), compared with mUW, and mUW+adenosine regenerated +35.6% (P<0.05) more beta-NTP, compared with mUW. Storage for 16 hr did not slow the rates of regeneration, and the total NTP produced during the course of the experiment remained unchanged for the respective preservation solutions. Cessation of HtR invoked a net accumulation of nucleotide diphosphate, indicating differential kinetics of adenine nucleotide hydrolysis. CONCLUSION: This large animal model study suggests significant improvements to human organ preservation solutions using prostacyclin analogues and adenosine with respect to hepatic bioenergetics.
Adenine Nucleotides↗
Brain bioenergetics in murine models of scrapie using in vivo 31P magnetic resonance spectroscopy.
The bioenergetic status of the brain in scrapie mouse models was investigated during the late, clinical phase of the disease, by in vivo phosphorus magnetic resonance spectroscopy (MRS). The only significant change observed in the scrapie-infected mice compared with controls was an increase in intracellular brain pH (7.20+/-0.06 vs 7.10+/-0.05). No other changes in energetic metabolism were observed in the infected mice beside a trend in the decrease of phosphomonoester (PME) level, possibly associated with an alteration in glycolytic intermediates. This study showed that even in the presence of severe cellular vacuolation and microglia infiltrate, cerebral bioenergetic is maintained.
Adenosine Triphosphate↗
Mechanisms by which elevated intracellular calcium induces S49 cell membranes to become susceptible to the action of secretory phospholipase A2.
Exposure of S49 lymphoma cells to exogenous group IIA or V secretory phospholipase A2 (sPLA2) caused an initial release of fatty acid followed by resistance to further hydrolysis by the enzyme. This refractoriness was overcome by exposing cells to palmitoyl lysolecithin. This effect was specific in terms of lysophospholipid structure. Induction of membrane susceptibility by lysolecithin involved an increase in cytosolic calcium and was duplicated by incubating the cells with calcium ionophores such as ionomycin. Lysolecithin also activated cytosolic phospholipase A2 (cPLA2). Inhibition of this enzyme attenuated the ability of lysolecithin (but not ionomycin) to induce susceptibility to sPLA2. Lysolecithin or ionomycin caused concurrent hydrolysis of both phosphatidylethanolamine and phosphatidylcholine implying that transbilayer movement of phosphatidylethanolamine occurred upon exposure to these agents but that susceptibility is not simply due to exposure of a preferred substrate (i.e. phosphatidylethanolamine) to the enzyme. Microvesicles were apparently released from the cells upon addition of lysolecithin or ionomycin. Both these vesicles and the remnant cell membranes were susceptible to sPLA2. Together these data suggest that lysolecithin induces susceptibility through both cPLA2-dependent and -independent pathways. Whereas elevated cytosolic calcium was required for both pathways, it was sufficient only for the cPLA2-independent pathway. This cPLA2-independent pathway involved changes in cell membrane structure associated with transbilayer phospholipid migration and microvesicle release.
Calcium↗
Incorporation of metabolite prior knowledge for data analysis: biochemical implications of dynamic 31P NMR ex vivo pig liver studies.
A semi-automated, metabolite prior-knowledge-based, lineshape fitting analysis has been developed to assess the dynamic biochemical changes found in ex vivo 31P NMR pig liver preservation studies. Due to the inherent experimental limitations of the ex vivo study and the complexity of the composite phosphorus resonances, metabolite information obtained in vitro was incorporated into the ex vivo analysis. This approach has allowed complete metabolite analysis (phosphomonoesters, inorganic phosphate, phosphodiesters and nucleotide triphosphates) in over 2000 spectra in a fraction of the time compared with more conventional analysis methods. The developed analysis will enable complete and rapid assessment of the biochemical changes in ongoing cold preservation studies of the pig liver which will result in thousands of ex vivo 31P NMR spectra. It is also envisaged that comparative studies on human donor livers will be carried out, in which this type of analysis would be the method of choice. Moreover, this kind of analysis approach could be advantageous in many complex in vivo NMR spectroscopy applications.
Animals↗
Relation of triglyceride stores in skeletal muscle cells to central obesity and insulin sensitivity in European and South Asian men.
AIMS/HYPOTHESIS: To compare the relation between intramyocellular lipid content, central obesity and insulin sensitivity in Europeans and South Asians. METHODS: Cross-sectional study of 40 South Asian and European non-diabetic men matched for age and body mass index. We measured intramyocellular lipid by proton magnetic resonance spectroscopy of soleus muscle, insulin sensitivity by the short insulin tolerance test, per cent body fat by dual-energy x-ray absorptiometry and visceral fat by single-slice computed tomography of the abdomen. RESULTS: South Asians compared with Europeans had a higher mean per cent body fat (26.8% vs 22.5%, p = 0.05) and lower insulin sensitivity (mean +/- SEM 2.4 +/- 0.2 vs 3.4%/min +/- 0.3, p = 0.013). Mean (+/- SEM) intramyocellular lipid content was higher in South Asians than in Europeans (72.1 +/- 7.5 vs 53.6 +/- 4.9 mmol/kg dry weight, p = 0.046). In Europeans intramyocellular lipid was correlated with per cent body fat (r = 0.50, p = 0.028), waist:hip ratio (r = 0.74, p < 0.001), visceral fat (r = 0.62, p = 0.004) and insulin sensitivity (r = -0.53, p = 0.016). In South Asians intramyocellular lipid was not significantly related to insulin sensitivity or obesity, and the strongest associations of insulin sensitivity were with fasting plasma triglyceride and waist:hip ratio. CONCLUSION/INTERPRETATION: The association of intramyocellular lipid with insulin sensitivity and obesity in Europeans is consistent with the hypothesis that muscle triglyceride mediates the effect of obesity on insulin sensitivity. The absence of a similar relation of insulin sensitivity to intramyocellular lipid in South Asians suggests that other mechanisms underlie the high insulin resistance observed in this group.
Absorptiometry, Photon↗
Relation between proton magnetic resonance spectroscopy within 18 hours of birth asphyxia and neurodevelopment at 1 year of age.
The aim of the study was to test the hypotheses that elevated cerebral lactate, detected by proton spectroscopy performed within 18 hours of suspected birth asphyxia, is associated with adverse outcome, and that increased lactate can be used to predict adverse outcome. Thirty-one term infants suspected of having had birth asphyxia and seven control infants underwent proton magnetic resonance spectroscopy, using three-dimensional chemical shift imaging, within 18 hours of birth. Adverse outcome was defined as death or neurodevelopmental impairment at 1 year of age or more. Nine infants had an adverse outcome. The other 22 and all of the control infants remained normal. Median (range) lactate/creatine plus phosphocreatine (lactate/creatine) ratios in the abnormal, the normal, and the control group were 1.14 (0.17 to 3.81), 0.33 (0 to 1.51), and 0.05 (0 to 0.6) respectively (P=0.003). Lactate/creatine >1.0 predicted neurodevelopmental impairment at 1 year of age with sensitivity of 66% and specificity of 95%, positive and negative predictive values of 86% and 88%, and a likelihood ratio of 13.2. Elevated cerebral lactate/creatine within 18 hours of birth asphyxia predicts adverse outcome.
Asphyxia Neonatorum↗